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Sample records for standard antiepileptic drugs

  1. Treatment of hypopituitarism in patients receiving antiepileptic drugs.

    Science.gov (United States)

    Paragliola, Rosa Maria; Prete, Alessandro; Kaplan, Peter W; Corsello, Salvatore Maria; Salvatori, Roberto

    2015-02-01

    Evidence suggests that there may be drug interactions between antiepileptic drugs and hormonal therapies, which can present a challenge to endocrinologists dealing with patients who have both hypopituitarism and neurological diseases. Data are scarce for this subgroup of patients; however, data for the interaction of antiepileptic drugs with the pituitary axis have shown that chronic use of many antiepileptic drugs, such as carbamazepine, oxcarbazepine, and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations of sex hormones. Other antiepileptic drugs increase sex hormone-binding globulin, which reduces the bioactivity of testosterone and estradiol. Additionally, the combined oestrogen-progestagen contraceptive pill might decrease lamotrigine concentrations, which could worsen seizure control. Moreover, sex hormones and their metabolites can directly act on neuronal excitability, acting as neurosteroids. Because carbamazepine and oxcarbazepine can enhance the sensitivity of renal tubules, a reduction in desmopressin dose might be necessary in patients with central diabetes insipidus. Although the effects of antiepileptic drugs in central hypothyroidism have not yet been studied, substantial evidence indicates that several antiepileptic drugs can increase thyroid hormone metabolism. However, although it is reasonable to expect a need for a thyroxine dose increase with some antiepileptic drugs, the effect of excessive thyroxine in lowering seizure threshold should also be considered. There are no reports of significant interactions between antiepileptic drugs and the efficacy of human growth hormone therapy, and few data are available for the effects of second-generation antiepileptic drugs on hypopituitarism treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Rhabdomyolysis induced by antiepileptic drugs: characteristics, treatment and prognosis.

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    Jiang, Wei; Wang, Xuefeng; Zhou, Shengnian

    2016-01-01

    Rhabdomyolysis syndrome refers to a variety of factors that affect the striated muscle cell membrane, the membrane channels and its energy supply. Most cases of rhabdomyolysis are due to direct trauma. However, infection, toxins, drugs, muscle ischemia, electrolyte imbalance, metabolic diseases, genetic diseases and abnormal body temperature can also lead to rhabdomyolysis. Epilepsy is one of the most common chronic neurological diseases. The primary long-term treatment is antiepileptic drugs (AEDs), which may cause rhabdomyolysis. This article summarizes the characteristics, treatment methods and prognosis of patients with rhabdomyolysis that is induced by antiepileptic drugs. This review is based on PubMed, EMBASE and MEDLINE searches of the literature using the keywords "epilepsy", "antiepileptic drugs","status epilepticus","rhabdomyolysis", and "antiepileptic drugs and rhabdomyolysis syndrome" as well as extensive personal clinical experience with various antiepileptic drugs. Potential relationships between antiepileptic drugs and rhabdomyolysis are discussed. Worldwide, there are approximately 50 million epilepsy patients, most of whom are treated with drugs. Reports have indicated that the majority of antiepileptic drugs on the market can cause rhabdomyolysis. Although rhabdomyolysis induced by antiepileptic drugs is a rare condition with a low incidence, this condition has serious consequences and merits attention from clinicians.

  3. Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

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    Stefanović, Srđan; Janković, Slobodan M; Novaković, Milan; Milosavljević, Marko; Folić, Marko

    2018-02-01

    Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

  4. [Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience].

    Science.gov (United States)

    Serragui, Samira; Zalagh, Fatima; Tanani, Driss Soussi; Ouammi, Lahcen; Moussa, Latifa Ait; Badrane, Narjis; Bencheikh, Rachida Soulaymani

    2016-01-01

    The therapeutic drug monitoring (TDM) of antiepileptic drugs is a tool widely used in the management of epilepsy. In Morocco, this monitoring is carried out by the Centre Anti Poison et Pharmacovigilance (CAPM) since April 1995. This is a retrospective study spanning 20 years. It concerns the therapeutic drug monitoring of Phenobarbital (PB) of carbamazepine (CBZ) and valproic acid (VPA). Therapeutic drug monitoring of the 3 antiepileptic drugs represent 58.85% of all applications received by the CAPM. The dosage of PB was ranked first followed by that of CBZ and finally by the VPA. Weak demand for therapeutic drug monitoring in Morocco could be explained by the low number of neurologists in addition to social factors. With its affordable price by patients, PB is the most prescribed antiepileptic drug in our country, which explains the high demand for its dosage. As for the therapeutic drug monitoring of the antiepileptic drug, they were mainly related to age, the occurrence of adverse effects, the association antiepileptic drugs or in the case of verification of patient compliance. Efforts are required for promoting the interests of therapeutic drug monitoring of antiepileptic drug in the management of epilepsy in Morocco.

  5. Basic Mechanisms of Action of the Antiepileptic Drugs

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    Kuzmanova R.

    2017-10-01

    Full Text Available Available antiepileptic drugs interact with a variety of different molecular targets. The mechanism of action of most anticonvulsants is most often complex with a number of affected regions. The combination of mechanisms of action of drugs in particular proportions can possibly determine the showcase of its antiepileptic activity. The common factor between the different supposed mechanisms for a number of drugs includes the possibility for modulating the excitatory and inhibitory neurotransmission through effects upon the voltage-gated ion channels, synaptic plasticity, heterogeneous receptors, and metabolism of neurotransmitters. There are controversial data on the extent to which a specific action can be the reason for the wholesome anticonvulsive characteristics of various medications, as well as the relation with the presence of undesired drug effects. The complexity of the action of some antiepileptic drugs creates conditions for optimal choice during therapy. In many cases, the insufficient familiarity with individual genetic differences and the disease related receptor damages can hinder defining a particular drug action. Characterizing the mechanisms of action of the present antiepileptic medications would increase the understanding for the pathophysiological mechanisms of epileptic seizures, as well as the development of new therapeutic strategies. The development of novel antiepileptic drugs and the ongoing research regarding the mechanism of action of established antiepileptic drugs, are continuously increasing the level of complexity in the spectrum of molecular targets relevant for epilepsy therapy. The current state of knowledge as well as the limitations in our understanding should guide future research aiming for a more detailed elucidation of the impact of genetics and pathophysiological mechanisms on interindividual differences in expression and function of antiepileptic drug targets.

  6. Pharmacokinetics of Anti-Epileptic Drugs and their Clinical Significance

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    Svein I. Johannessen

    1990-01-01

    Full Text Available The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ.

  7. Antiepileptic drugs and bone metabolism

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    Labban Barbara

    2006-09-01

    Full Text Available Abstract Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population.

  8. The effects of antiepileptic drugs on the growth of glioblastoma cell lines

    OpenAIRE

    Lee, Ching-Yi; Lai, Hung-Yi; Chiu, Angela; Chan, She-Hung; Hsiao, Ling-Ping; Lee, Shih-Tseng

    2016-01-01

    To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levet...

  9. Access to antiepileptic drug therapy in children in Camagüey Province, Cuba

    Science.gov (United States)

    Arencibia, Zeina Bárzaga; Leyva, Alberto López; Peña, Yordanka Mejías; Reyes, Alba Rosa González; Nápolez, Maurilys Acosta; Carbonell Perdomo, Demetrio; Manzano, Edita Fernández; Choonara, Imti

    2012-01-01

    Objective To describe access to antiepileptic drug therapy and estimate the prevalence of epilepsy in children in Camagüey Province, Cuba. Methods All the community pharmacies in the province were visited and information collected about the number of children receiving antiepileptic drugs in 2009. Availability and cost of each antiepileptic drug were determined. The prevalence of epilepsy was estimated by determining the number of children receiving antiepileptic drugs. Results There were 923 children who received a total of 977 antiepileptic drugs in Camagüey Province. The estimated prevalence of epilepsy was 5.18 per thousand children which is lower than previously reported rates in other low and lower-middle income countries. Most of the children (871, 94%) received a single antiepileptic drug. Carbamazepine and valproate were the two most frequently prescribed antiepileptic drugs. Antiepileptic drugs were available from the local pharmacy on 76% of occasions. If the antiepileptic drug was not available from the local pharmacy, the parent had to travel to another pharmacy to obtain the medicine. Conclusions The estimated prevalence of epilepsy in children in Cuba is lower than that estimated in other lower-middle income countries. Access to drug therapy in children with epilepsy can be achieved in lower-middle income countries. PMID:23134098

  10. Short-term use of antiepileptic drugs is neurotoxic to the immature brain

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    Yu Liu

    2015-01-01

    Full Text Available Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to infants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3-21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hematoxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the combination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our findings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

  11. Psychopharmacological treatment with lithium and antiepileptic drugs

    DEFF Research Database (Denmark)

    Licht, R W; Vestergaard, P; Kessing, L V

    2003-01-01

    A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing...... to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed......, outlining the scientific evidence for mood-stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly...

  12. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    Qiao, X.

    2013-01-01

    Certain antiepileptic drugs (e.g. carbamazepine and lamotrigine) block sodium channels in an use-dependent manner and this mechanism contributes to the anti-convulsant properties of these drugs. There are, however, subtle differences in sodium current blocking properties of the antiepileptic drugs

  13. Intravenous Antiepileptic Drugs in Russia

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    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  14. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

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    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  15. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

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    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  16. Derangement of lipid profile in antiepileptic drugs treated patients in local population

    International Nuclear Information System (INIS)

    Zuberi, N.A.; Perveen, T.

    2012-01-01

    Epilepsy is the third most common neurological disorder. It is not a single entity. The abnormal electrical activity may result in a variety of events, including loss of consciousness, abnormal movements, a typical or odd behavior or distorted perceptions falls seizers. Epilepsy is a chronic disorder and often requiring years of treatment. A large number of drugs are used for the treatment of epilepsy. The choice among the antiepileptic drugs depends on its effectiveness and side effects. Our retrospective study investigated the effect of anti epileptic drugs on lipid profile. Serum lipid profile was measured in 160 patients in which 40 patients were not started any antiepileptic drug .The remaining 120 patients were receiving antiepileptic drugs (AEDs). 40 control subjects were taken from general population for comparison. The height, weight and body mass index (BMI) and lipid profile of antiepileptic drugs treated patients were compared with control and untreated group. The weight and body mass index of antiepileptic drugs treated group was significantly increased when compared to the control group. Total Cholesterol (TC), Triglyceride (TO), High density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ratio TC/HDL-C and ratio LDL-C/HDL-C were investigated for each group of drugs and controls. TC, TO, LDL-C, ratio TC/HDL-C and ratio LDL-C/HDL-C were significantly increased in patients who were on AEDs when compared with control but HDL-C of all drug treated groups showed significantly decreased when compared with control group. There was significant change in lipid profile was seen in AEDs treated group when compared with control group. Ratio TC/HDL-C and ratio LDUHDL-C alteration showed the risk of atherosclerosis and cardiovascular diseases. Anti-epileptic drugs also alter the BMI and so it could potentially facilitate the development of diabetes mellitus. Our results additionally suggest that there is a need for careful monitoring of lipid profile in

  17. Analysis of antiepileptic drugs in biological fluids by means of electrokinetic chromatography.

    Science.gov (United States)

    Pucci, Vincenzo; Raggi, Maria Augusta

    2005-02-01

    An overview of the electrokinetic chromatographic methods for the analysis of antiepileptic drug levels in biological samples is presented. In particular, micellar electrokinetic capillary chromatography is a very suitable method for the determination of these drugs, because it allows a rapid, selective, and accurate analysis. In addition to the electrokinetic chromatographic studies on the determination of antiepileptic drugs, some information regarding sample pretreatment will also be reported: this is a critical step when the analysis of biological fluids is concerned. The electrokinetic chromatographic methods for the determination of recent antiepileptic drugs (e.g., lamotrigine, levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin, ethosuximide, valproic acid) will be discussed in depth, and their pharmacological profiles will be briefly described as well.

  18. Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

    International Nuclear Information System (INIS)

    Myllynen, Paeivi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-01-01

    Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placental transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure

  19. Co-prescription of antiepileptic drugs and contraceptives

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    Wang, H.; Bos, J.H.; de Jong-van den Berg, L.T.

    Background: Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive-age women who receive AEDs. Study Design: We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with

  20. Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients.

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    Salih, Muhannad R M; Bahari, Mohd Baidi; Abd, Arwa Y

    2010-12-31

    To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010) for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics) interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This reassessment may be particularly imperative in certain clinical situations

  1. Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral nutrition in critically ill patients

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    Abd Arwa Y

    2010-12-01

    Full Text Available Abstract Objectives To conduct a systematic review for the evidence supporting or disproving the reality of parenteral nutrition- antiepileptic drugs interaction, especially with respect to the plasma protein-binding of the drug. Methods The articles related to the topic were identified through Medline and PubMed search (1968-Feburary 2010 for English language on the interaction between parenteral nutrition and antiepileptic drugs; the search terms used were anti-epileptic drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search looked for prospective randomized and nonrandomized controlled studies; prospective nonrandomized uncontrolled studies; retrospective studies; case reports; and in vitro studies. Full text of the articles were then traced from the Universiti Sains Malaysia (USM library subscribed databases, including Wiley-Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals not listed by USM library were traced through inter library loan. Results There were interactions between parenteral nutrition and drugs, including antiepileptics. Several guidelines were designed for the management of illnesses such as traumatic brain injuries or cancer patients, involving the use of parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the in vitro and in vivo parenteral nutrition -drugs interactions, especially with antiepileptics. Conclusions There was no evidence supporting the existence of parenteral nutrition-antiepileptic drugs interaction. The issue has not been studied in formal researches, but several case reports and anecdotes demonstrate this drug-nutrition interaction. However, alteration in the drug-free fraction result from parenteral nutrition-drug (i.e. antiepileptics interactions may necessitate scrupulous reassessment of drug dosages in patients receiving these therapies. This

  2. Interactions between hormonal contraception and antiepileptic drugs

    DEFF Research Database (Denmark)

    Reimers, Arne; Brodtkorb, Eylert; Sabers, Anne

    2015-01-01

    Antiepileptic drugs (AEDs) and hormonal contraceptives may affect each other's metabolism and clinical efficacy. Loss of seizure control and unplanned pregnancy may occur when these compounds are used concomitantly. Although a large number of available preparations yield a plethora of possible drug...... combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, there is a substantial lack of data regarding the newer AEDs. Detailed understanding of these issues is necessary for those who prescribe AEDs and/or hormonal contraception to women with epilepsy, as well...

  3. Interactions between antiepileptic drugs and hormones.

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    Svalheim, Sigrid; Sveberg, Line; Mochol, Monika; Taubøll, Erik

    2015-05-01

    Antiepileptic drugs (AEDs) are known to have endocrine side effects in both men and women. These can affect fertility, sexuality, thyroid function, and bone health, all functions of major importance for well-being and quality of life. The liver enzyme inducing antiepileptic drugs (EIAEDs), like phenobarbital, phenytoin, and carbamazepine, and also valproate (VPA), a non-EIAED, are most likely to cause such side effects. AED treatment can alter the levels of different sex hormones. EIAEDs increase sex hormone binding globulin (SHBG) concentrations in both men and women. Over time, this elevation can lead to lower levels of bioactive testosterone and estradiol, which may cause menstrual disturbances, sexual problems, and eventually reduced fertility. VPA can cause weight gain in both men and women. In women, VPA can also lead to androgenization with increased serum testosterone concentrations, menstrual disturbances, and polycystic ovaries. Lamotrigine has not been shown to result in endocrine side effects. The newer AEDs have not yet been thoroughly studied, but case reports indicate that some of these drugs could also be suspected to cause such effects if endocrine changes commence after treatment initiation. It is important to be aware of possible endocrine side effects of AEDs as they can have a major impact on quality of life, and are, at least partly, reversible after AED discontinuation. Copyright © 2015. Published by Elsevier Ltd.

  4. Levels of Antiepileptic Drugs and the Ketogenic Diet

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    J Gordon Millichap

    2006-08-01

    Full Text Available Introduction of the ketogenic diet did not change the plasma levels of antiepileptic drugs in an open study of 51 children (mean age 6.6 years with refractory epilepsy studied at Karolinska University Hospital, Stockholm, Sweden.

  5. Managing antiepileptic drugs during pregnancy and lactation

    DEFF Research Database (Denmark)

    Sabers, Anne; Tomson, Torbjörn

    2009-01-01

    PURPOSE OF REVIEW: This review discusses data on the pharmacokinetics of antiepileptic drugs (AEDs) in pregnancy and lactation, and the clinical consequences thereof, thus providing a basis for a rational management of AEDs during pregnancy and lactation. RECENT FINDINGS: Studies have confirmed...... of AEDs in pregnancy and during lactation is important to enable optimal treatment. Gestation induced alterations in pharmacokinetics vary with the AED but also between patients and are difficult to predict. Therapeutic drug monitoring is, therefore, advisable during pregnancy and the use...... of the individual patient's optimal prepregnancy drug level is recommended as reference. Breastfeeding is in general safe but needs appropriate observation of the nursing infant....

  6. Selection criteria for the clinical use of the newer antiepileptic drugs.

    NARCIS (Netherlands)

    Deckers, C.L.P.; Knoester, P.D.; Haan, G.J. de; Keyser, A.J.M.; Renier, W.O.; Hekster, Y.A.

    2003-01-01

    In recent years, several new antiepileptic drugs (AEDs) have been licensed: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide. These drugs have proven efficacy as add-on therapy in patients with difficult-to-treat partial epilepsy, as

  7. The Effects of Antiepileptic Drugs on Classroom Performance

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    Titus, Jeffrey B.; Thio, Liu Lin

    2009-01-01

    Epilepsy is one of the most common neurological disorders in children, and it has been associated with an increased risk of cognitive, psychiatric, and learning problems. Although side effects of antiepileptic drugs (AEDs) have been long studied in adults, an understanding of how they manifest in children is only beginning to emerge. Careful…

  8. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...... of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible. (C) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/3...

  9. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, J.B.; Hansen, Peter Riis; Erdal, Jesper

    2010-01-01

    Purpose Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study inve...

  10. Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

    Science.gov (United States)

    Kalachnik, John E.; And Others

    1995-01-01

    Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

  11. COST ANALYSIS OF LONG ESTABLISHED AND NEWER ORAL ANTIEPILEPTIC DRUGS AVAILABLE IN THE INDIAN MARKET

    Directory of Open Access Journals (Sweden)

    Phatak Abhishek M, Hotwani Jitendra H, Deshmukhkiran R, Panchal Sagar S, Naik Madhura S

    2015-10-01

    Full Text Available Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Materials: Cost of a drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Indian Drug Review” Vol. XXI, Issue No.4, 2014 and “Current Index of Medical Specialties” July-October 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price was calculated. Results: The percentage price variation noted of long-established drugs was – Phenytoin (50mg: 140%, Carbamazepine (100mg: 1033%, Phenobarbital (30mg : 730%, Valproic acid (300mg : 420%. Newer drugs –Levetiracetam (250mg: 75%, Lamotrigine (25mg: 66%, Topiramate (50mg: 108%, Zonisamide (100mg: 19%. Combination drugs – Phenobarbital + Phenytoin (30+100 mg: 354.55%. Conclusion: The percentage price variation of different brands of the same commonly used long-established oral antiepileptic drug manufactured in India is very wide. The formulation or brand of Antiepileptic drugs (AED’s should preferably not be changed since variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects. Hence, manufacturing companies should aim to decrease the price variation while maintaining the therapeutic efficacy.

  12. The challenges of treating epilepsy with 25 antiepileptic drugs.

    Science.gov (United States)

    Santulli, Lia; Coppola, Antonietta; Balestrini, Simona; Striano, Salvatore

    2016-05-01

    Nowadays a substantial armamentarium of antiepileptic drugs (AEDs) is available, including drugs with different mechanisms of action, pharmacokinetics, efficacy and tolerability; therefore the choice for the right treatment is often challenging. The specific characteristic of the drug, the epileptic syndrome, seizure types and the patient's features need to be taken into consideration driving the choice through available evidence-based studies, which are often lacking for older AEDs. Besides, study conditions in registered clinical trials (RCTs) are quite different from daily clinical practice, which is more complex and various. When dealing with first diagnosed epilepsy, monotherapy is widely accepted as the gold standard option. Likewise, alternative monotherapy should be considered when the first drug treatment fails. However, the association of different AEDs in polytherapy is a common practice. The choice of AEDs used in association is often based on clinical experience or anecdotal observations or small clinical studies. Polytherapy should be as "rational" as possible and consider the mechanism of action, the pharmacokinetic characteristics and the safety of each drug. When dealing with drug resistant patients, clinicians should never give up and consider the use of AEDs acting on new targets. An attempt to come back to a monotherapy or simpler therapeutic regimen should be pursued even in patients who were previously drug resistant. This review will focus on the strategies to treat epilepsy by choosing among 25 available drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Importance of competing risks in the analysis of anti-epileptic drug failure

    Directory of Open Access Journals (Sweden)

    Sander Josemir W

    2007-03-01

    Full Text Available Abstract Background Retention time (time to treatment failure is a commonly used outcome in antiepileptic drug (AED studies. Methods Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. Results A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91 masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007 but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001. The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018 was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001. Conclusion Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs.

  14. The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

    Science.gov (United States)

    Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

    2009-01-01

    Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

  15. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: An update

    OpenAIRE

    Kazmin, Aleksey; Wong, Renee C.; Sermer, Mathew; Koren, Gideon

    2010-01-01

    QUESTION What is the current evidence regarding the association between hemorrhagic disease of the newborn and maternal use of hepatic enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenobarbitone, topiramate)?

  16. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

    2014-01-01

    are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

  17. Severe overdosage with the antiepileptic drug oxcarbazepine

    Science.gov (United States)

    van Opstal, J M; Janknegt, R; Cilissen, J; L’Ortije, W H V M; Nel, J E; De Heer, F

    2004-01-01

    Few published human data are available concerning the acute toxicity of the new antiepileptic drug oxcarbazepine of which the metabolite 10- monohydroxy derivate (MHD) is the pharmacologically effective compound. Two hours after a documented overdosage of more than 100 tablets oxcarbazepine, the serum level of the parent compound was 10-fold higher than the therapeutic dosage (31.6 mg l−1). However, the concentration of MHD, which peaked 7 h after intake, was only twofold higher (59.0 mg l−1). No life-threatening situations occurred and the patient fully recovered. The fact that oxcarbazepine is a prodrug and that the formation of the active MHD metabolite is a rate-limiting process may contribute to the relative low toxicity of the drug in overdose. PMID:15327594

  18. The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

    Directory of Open Access Journals (Sweden)

    Carapella Maria Carmine

    2009-05-01

    Full Text Available Abstract Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population.

  19. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2011-01-01

    Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital ...

  20. Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

    Science.gov (United States)

    Herzog, Andrew G; Mandle, Hannah B; Cahill, Kaitlyn E; Fowler, Kristen M; Hauser, W Allen

    2016-07-01

    The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (pcontraception (4.2%) was 4.47 (pcontraception (5.5%) was 1.71, pcontraception, the risk ratio for seizure increase was greater than for decrease (1.98, pmethod with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (pcontraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category. Copyright © 2016. Published by Elsevier Inc.

  1. [Social aspects of epilepsy: marriage, pregnancy, driving, antiepileptic drug withdrawal and against social stigma].

    Science.gov (United States)

    Tsuji, Sadatoshi

    2004-11-01

    Persons with epilepsy need adequate advice and effective counselling about issues such as marriage, pregnancy, risks of inheriting epilepsy, driving, employment and antiepileptic drug withdrawal, because these persons are not receiving important information and education about their condition and possible adverse effects of treatment. Furthermore, women with epilepsy have increased rates of pregnancy complications and poor fetal outcomes including congenital malformations and developmental delay related to both their epilepsy and antiepileptic drugs. However, approximately 90% of all women with epilepsy undergo normal pregnancy and give birth to children free of birth defects. Pregnancy is generally safe in women with epilepsy. The study of long-term prognosis of childhood-onset epilepsy in Japan shows that the majority of these patients have lower levels of educational background as well as employment and marital status compared with the general population (Wakamoto H. et al). Of patients with epilepsy, 60% to 70% achieve control with antiepileptic medication. However, several antiepileptic drug withdrawal studies show variable rates of success, with relapse rates ranging from 12% to 63% (Britton J.W.). Driving is listed as major problem in persons with epilepsy. However, the patients with seizure-free more than two years have been able to get the driver's license since June, 2002. Social attitudes towards epilepsy cause more distress to the patient than the disease itself. We should realize that persons with epilepsy are normal or near-normal. To ameliorate the social stigma against epilepsy, continuous and repetitive educational efforts would be needed.

  2. Neurodevelopmental Effects of Antiepileptic Drugs.

    Science.gov (United States)

    Kellogg, Marissa; Meador, Kimford J

    2017-07-01

    Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.

  3. Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery

    NARCIS (Netherlands)

    Boshuisen, Kim; van Schooneveld, Monique M. J.; Uiterwaal, Cuno S. P. M.; Cross, J. Helen; Harrison, Sue; Polster, Tilman; Daehn, Marion; Djimjadi, Sarina; Yalnizoglu, Dilek; Turanli, Guzide; Sassen, Robert; Hoppe, Christian; Kuczaty, Stefan; Barba, Carmen; Kahane, Philippe; Schubert-Bast, Susanne; Reuner, Gitta; Bast, Thomas; Strobl, Karl; Mayer, Hans; de Saint-Martin, Anne; Seegmuller, Caroline; Laurent, Agathe; Arzimanoglou, Alexis; Braun, Kees P. J.

    ObjectiveAntiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long-term seizure outcomes. We now aimed to evaluate the effect of

  4. Determination of Four Anti-epileptic Drugs in Plasma Using Ultra Performance Liquid Chromatography with Mass Detection Technique.

    Science.gov (United States)

    Hassib, Sonia T; Hashem, Hanaa M A; Mahrouse, Marianne A; Mostafa, Eman A

    2018-04-10

    Status epilepticus (SE) is considered the second most frequent neurologic emergency. Its therapeutic management is performed using sequential anti-epileptic drug regimens. Diazepam (DIA), midazolam (MID), phenytoin (PHT) and phenobarbital (PB) are four drugs of different classes used sequentially in the management of SE. A sensitive, selective, accurate and precise method was developed and validated for simultaneous determination of the four anti-epileptic drugs in human plasma. Their separation and quantification were achieved using ultra performance liquid chromatography (UPLC) with mass detection using carbamazepine as internal standard (IS). For the first three drugs and IS, UPLC-MS/MS with electrospray ionization working in multiple reaction monitoring mode was used at the following transitions: m/z 285→193 for DIA, m/z 326→291 for MID, m/z 253→182 for PHT and m/z 237→194, 237→192 for IS. For the fourth drug (PB), molecular ion peak of PB [M+H] + at m/z 233 was used for its quantitation. The method was linear over concentration ranges of 5-500 ng/ml for DIA and MID and 0.25-20 μg/ml for PHT and PB, respectively. Bio-analytical validation of the developed method was carried out according to European Medicines Agency guidelines. The developed method can be applied for routine drug analysis, therapeutic drug monitoring and bioequivalence studies. This article is protected by copyright. All rights reserved.

  5. Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

    Science.gov (United States)

    Levin, Harvey S.; Chiang, Sharon

    2015-01-01

    Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

  6. Antiepileptic drugs for chronic non-cancer pain in children and adolescents.

    Science.gov (United States)

    Cooper, Tess E; Wiffen, Philip J; Heathcote, Lauren C; Clinch, Jacqui; Howard, Richard; Krane, Elliot; Lord, Susan M; Sethna, Navil; Schechter, Neil; Wood, Chantal

    2017-08-05

    Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews as well as online clinical trial registries. Randomised controlled trials, with or without blinding, by any route, treating chronic non-cancer pain in children and adolescents, comparing any antiepileptic drug with placebo or an active comparator. Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods if data were available. We assessed the evidence using GRADE and created two 'Summary of findings' tables. We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis.Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomesOne study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes (very low-quality evidence).The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no

  7. The Australian Register of Antiepileptic Drugs in Pregnancy : The first 1002 pregnancies

    NARCIS (Netherlands)

    Vajda, Frank J. E.; Hitchcock, Alison; Graham, Janet; O'Brien, Terence; Lander, Cecilie; Eadie, Mervyn

    2007-01-01

    Prospective studies are needed to assess the maternal and fetal hazards of antiepileptic drug (AED) therapy in pregnancy. To make the Australian Register of AEDs in Pregnancy better known to the Australian obstetric community by presenting results derived from it. Analysis of data collected by the

  8. Preventive Agents for Migraine: Focus on the Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    R. Shahien

    2012-04-01

    Full Text Available Migraine is among the 10 most disabling disorders worldwide. It is characterized by episodes of moderate or severe headaches with various degree of disability, resulting in a considerable health burden upon the sufferers and their family. The objective of this article is to review the use of prophylaxis with antiepileptic drugs. Particular focus is given to their mechanism of action, metabolism, pharmacokinetics, safety profile, efficacy and to provide a summary of the most relevant clinical studies and patient preference.

  9. The effect of antiepileptic drugs on cognitive functions

    Directory of Open Access Journals (Sweden)

    A. S. Kotov

    2013-01-01

    Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

  10. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects.

    Science.gov (United States)

    Sequerra, Eduardo B; Goyal, Raman; Castro, Patricio A; Levin, Jacqueline B; Borodinsky, Laura N

    2018-05-16

    Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy. Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.

  11. Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; White, H Steve; Schousboe, Arne

    2010-01-01

    of transmembrane transport and enzymatic degradation. The development of tiagabine selectively inhibiting the GABA transporter GAT1 constitutes a proof of concept that the GABA transporters are interesting drug targets in the context of antiepileptic drugs. The review provides a detailed analysis of the role......,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) has been shown to possess a novel anticonvulsant profile in animal models of epilepsy, involving the ability to inhibit GABA transport mediated by GAT1 and BGT1 at the same time....

  12. Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

    Science.gov (United States)

    Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

    2017-01-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Assessing suicidal risk with antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Marco Mula

    2010-09-01

    Full Text Available Marco Mula2, Gail S Bell1, Josemir W Sander1,31Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, and National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust, London, United Kingdom; 2Department of Clinical and Experimental Medicine, Division of Neurology, Amedeo Avogadro University, University Hospital Maggiore della Carità, Novara, Italy; 3SEIN – Epilepsy Institute in the Netherlands Foundation, Heemstede, The NetherlandsAbstract: Recently, the US Food and Drug Administration issued an alert about an increased risk for suicidality during treatment with antiepileptic drugs (AEDs for different indications, including epilepsy. We discuss the issue of suicide in epilepsy with special attention to AEDs and the assessment of suicide in people with epilepsy. It has been suggested that early medical treatment with AEDs might potentially reduce suicide risk of people with epilepsy, but it is of great importance that the choice of drug is tailored to the mental state of the patient. The issue of suicidality in epilepsy is likely to represent an example of how the underdiagnosis of psychiatric symptoms, the lack of input from professionals (eg, psychologists, social workers, and psychiatrists, and the delay in an optimized AED therapy may worsen the prognosis of the condition with the occurrence of severe complications such as suicide.Keywords: epilepsy, suicide, adverse effect, depression

  14. Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence Reviewed

    NARCIS (Netherlands)

    Deckers, C.L.P.; Czuczwar, S.J.; Hekster, Y.A.; Keyser, A.J.M.; Kubova, H.; Meinardi, H.; Patsalos, P.N.; Renier, W.O.; Rijn, C.M. van

    2000-01-01

    Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried so as to improve effectiveness, by improving either efficacy, or tolerability, or both. We have reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be

  15. Enzyme induction in neonates after fetal exposure to antiepileptic drugs

    International Nuclear Information System (INIS)

    Rating, D.; Jaeger-Roman, E.; Nau, H.; Kuhnz, W.; Helge, H.

    1983-01-01

    The 13 C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to 13 C-AP breath tests, neonates have a very low capacity to eliminate 13 CO 2 , which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs 13 C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, 13 C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by 13 C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between 13 C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the 13 C breath test data will transport very different informations about enzyme induction in these neonates

  16. Chronic antiepileptic drug use and functional network efficiency : a functional magnetic resonance imaging study

    NARCIS (Netherlands)

    van Veenendaal, T.M.; IJff, D.M.; Aldenkamp, A.P.; Lazeron, R.H.C.; Hofman, P.A.M.; de Louw, A.J.A.; Backes, W.H.; Jansen, J.F.A.

    2017-01-01

    AIM: To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. METHODS: The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients

  17. Antiepileptic drug use in seven electronic health record databases in Europe: a methodological comparison.

    NARCIS (Netherlands)

    Groot, M.C.H. de; Schuerch, M.; Vries, F. de; Hesse, U.; Oliva, B.; Huerta Alvarez, C.; Gil, M.; Requena, G.; Abajo, F.; Afonso, A.; Souverein, P.C.; Alvarez, Y.; Slattery, J.; Rottenkolber, M.; Schmiedl, S.; Dijk, L. van; Schlienger, R.; Reynolds, R.; Klungel, O.

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  18. Antiepileptic drug use in seven electronic health record databases in europe: A methodological comparison

    NARCIS (Netherlands)

    De Groot, Mark C.H.; Schuerch, Markus; De Vries, Frank; Hesse, Ulrik; Oliva, Belén; Alvarez, Consuelo Huerta; Gil, Miguel; Requena, Gema; Abajo, Francisco; Afonso, Ana; Souverein, Patrick C.; Alvarez, Yolanda; Slattery, Jim; Rottenkolber, Marietta; Schmiedl, Sven; Van Dijk, Liset; Schlienger, Raymond G.; Reynolds, Robert; Klungel, Olaf

    2013-01-01

    Background: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries; this may be due to differences in type of data sources, time periods, population distributions, and methodology. Objectives: To assess the prevalence of

  19. Drug Interactions between some antiepileptic and certain hypocholesterolaemic drugs in irradiated animals

    International Nuclear Information System (INIS)

    Shaaban, D.M.L.

    2015-01-01

    Drug Interactions between antiepileptic drug such as phenytoin and certain hypercholesterolaemia drug namely rosuvastatin were investigated on several biological parameters. Phenytoin (60 mg/kg i.p) and rosuvastatin (1.25 mg/kg i.p) were given either alone and in combination to normal and irradiated animals to investigate drug interactions between the test drugs. Anticonvulsant activity was evaluated using pentylenetetrazole in a dose (80 mg/kg i.p) in normal and irradiated mice. Brain neurotransmitters (glutamate and GABA) were investigated. Lipid profile (total cholesterol (TC), Triacylglycerol (TG), High density lipoprotein-cholesterol (HDL-C) and low density lipoprotein- cholesterol (LDL-C) were determined. Liver functions such as serum Aspartate amino transferase (AST) and serum alanine amino transferase (ALT) were also estimated. Oxidative stress bio markers namely serum malondialdehyde (MDA), serum nitric oxide (NO) and blood superoxide dismutase activity (SOD) were studied. Histopathological examinations of brain and liver tissues were performed. Administration of phenytoin concurrently with rosuvastatin is not recommended in patients receiving radiotherapy as dangerous side effects on liver functions and lipid profile may occur. The interactions between the two drugs in normal rats improve liver functions and lipid peroxidation. Apart from the action of the combination on total cholesterol, it improves lipid profile pattern. Rosuvastatin administration in combination with phenytoin may have additive anticonvulsant activity.

  20. A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Ho, Karen S; Markham, Leah M; Twede, Hope; Lortz, Amanda; Olson, Lenora M; Sheng, Xiaoming; Weng, Cindy; Wassman, E Robert; Newcomb, Tara; Wassman, E Robert; Carey, John C; Battaglia, Agatino

    2018-04-01

    Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a psyndromes which may have complex seizure etiologies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Successful Treatment of Antiepileptic Drug-Induced DRESS Syndrome with Pulse Methylprednisolone

    Directory of Open Access Journals (Sweden)

    Celebi Kocaoglu

    2013-01-01

    Full Text Available Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome is a rare but potentially life-threatening syndrome characterized by skin rash, fever, lymph node enlargement, and involvement of internal organs. It is most commonly induced by aromatic anticonvulsants and antibiotics. Nonaromatic anticonvulsants are rarely encountered as the causes of DRESS syndrome. In the present report, three discrete cases with DRESS syndrome developing due to three antiepileptic drugs, including valproic acid (nonaromatic, carbamazepine (aromatic, and lamotrigine (aromatic, and their treatment modalities were aimed to be discussed in light of the literature. To the best of our knowledge, our cases are the first children to be treated with pulse methylprednisolone in the literature.

  2. Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

    Directory of Open Access Journals (Sweden)

    Berry Juliandi

    2015-12-01

    Full Text Available Prenatal exposure to valproic acid (VPA, an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running.

  3. Transient Splenial Lesion of Corpus Callosum Associated with Antiepileptic Drug: Conventional and Diffusion-weighted Magnetic Resonance Images

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, B.; Erdogan, C.; Yildirim, N.; Gokalp, G.; Parlak, M. [Uludag Univ. Medical School, Bursa (Turkey). Dept. of Radiology

    2005-11-01

    Transient focal lesions of splenium of corpus callosum can be seen as a component of many central nervous system diseases, including antiepileptic drug toxicity. The conventional magnetic resonance (MR) findings of the disease are characteristic and include ovoid lesions with high signal intensity at T2-weighted MRI. Limited information exists about the diffusion-weighted MRI characteristics of these lesions vanishing completely after a period of time. We examined the conventional, FLAIR, and diffusion-weighted MR images of a patient complaining of depressive mood and anxiety disorder after 1 year receiving antiepileptic medication.

  4. Prevention of Fetal Congenital Malformations with Allowance for the Pharmacogenetic Features of the Metabolism of Antiepileptic Drugs and Hereditary Abnormalities in the Folate Cycle

    Directory of Open Access Journals (Sweden)

    D. V. Dmitrenko

    2014-01-01

    Full Text Available Fetal congenital malformations are among the most dangerous complications of pregnancy in women with epilepsy taking antiepileptic drugs. Valproic acid and phenobarbital have the greatest risk of teratogenic effects. Insights into the current mechanisms of teratogenic effect of antiepileptic drugs, pharmacogenetic features of the metabolism of valproates and hereditary abnormalities in the folate cycle enables prevention of fetal congenital malformations. 

  5. Challenges in the clinical development of new antiepileptic drugs.

    Science.gov (United States)

    Franco, Valentina; French, Jacqueline A; Perucca, Emilio

    2016-01-01

    Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Newer anti-epileptic drugs, vitamin status and neuropathy: A cross-sectional analysis.

    Science.gov (United States)

    Cahill, V; McCorry, D; Soryal, I; Rajabally, Y A

    Whether new antiepileptic drugs (AEDs) may result in neuropathy is unknown but possible given their effects on vitamin metabolism. This analysis aimed to determine frequency and correlates of neuropathy in subjects treated with new AEDs in relation to drug used, length of exposure and serum vitamin B12 and folate levels. We performed a cross-sectional study of 52 consecutive epileptic subjects. Presence of neuropathy was determined using the Utah Early Neuropathy Score (UENS). Exposure to anti-epileptic drugs was quantified. Serum vitamin B12 and folate levels were measured. Commonly used AEDs were levetiracetam (28/52), carbamazepine (20/52), lamotrigine (20/52), sodium valproate (10/52) and zonisamide (10/52). Eight of 52 (15.4%) patients had neuropathy. There was no association with any particular AED. Neuropathy correlated with age (P=0.038) and total exposure to AEDs (P=0.032). UENS correlated with age (P=0.001), total AED exposure (P=0.001) and serum vitamin B12L (P=0.018). Independent association of neuropathy was found with total AED exposure (P=0.032), but not age. UENS was independently associated with total exposure to AEDs (Pvitamin B12L (P=0.002), but not age. Serum vitamin B12 and folate levels were highly inter-correlated (Pvitamin B12 and folate metabolism. Although further research from controlled studies is needed and despite the presence of other possible confounding factors, monitoring for neuropathy and vitamin B12 and folate levels merits consideration in patients on long-term treatment with new AEDs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

    Science.gov (United States)

    Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Exposure to antiepileptic drugs and the risk of hip fracture: a case-control study

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Nymark, Tine

    2008-01-01

    PURPOSE: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture. METHODS: We performed a case-control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals...... with a hip fracture during the period 1996-2004. Controls (n = 27,575) were frequency matched by age and gender. Information on use of AEDs, other drugs, and hospital contacts was available from local registers. Odds ratios (ORs) with 95% confidence intervals (CI) for hip fracture were estimated...

  9. Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

    Science.gov (United States)

    Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

    2015-07-01

    Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  10. The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

    OpenAIRE

    Munshi, Kaizad R.; Oken, Tanya; Guild, Danielle J.; Trivedi, Harsh K.; Wang, Betty C.; Ducharme, Peter; Gonzalez-Heydrich, Joseph

    2010-01-01

    Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the avail...

  11. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Abildstrøm, Steen Zabell; Erdal, Jesper

    2011-01-01

    Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).......Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs)....

  12. Utilization of antiepileptic drugs during pregnancy : Comparative patterns in 38 countries based on data from the EURAP registry

    NARCIS (Netherlands)

    Battino, D.; Bonizzoni, E.; Craig, J.; Lindhout, D.; Perucca, E.; Sabers, A.; Tomson, T.; Vajda, F.

    2009-01-01

    P>We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure

  13. Individualized prediction of seizure relapse and outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery.

    Science.gov (United States)

    Lamberink, Herm J; Boshuisen, Kim; Otte, Willem M; Geleijns, Karin; Braun, Kees P J

    2018-03-01

    The objective of this study was to create a clinically useful tool for individualized prediction of seizure outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery. We used data from the European retrospective TimeToStop study, which included 766 children from 15 centers, to perform a proportional hazard regression analysis. The 2 outcome measures were seizure recurrence and seizure freedom in the last year of follow-up. Prognostic factors were identified through systematic review of the literature. The strongest predictors for each outcome were selected through backward selection, after which nomograms were created. The final models included 3 to 5 factors per model. Discrimination in terms of adjusted concordance statistic was 0.68 (95% confidence interval [CI] 0.67-0.69) for predicting seizure recurrence and 0.73 (95% CI 0.72-0.75) for predicting eventual seizure freedom. An online prediction tool is provided on www.epilepsypredictiontools.info/ttswithdrawal. The presented models can improve counseling of patients and parents regarding postoperative antiepileptic drug policies, by estimating individualized risks of seizure recurrence and eventual outcome. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  14. Management of Antiepileptic Treatment After Epilepsy Surgery

    DEFF Research Database (Denmark)

    Rubboli, Guido; Sabers, Anne; Uldall, Peter

    2017-01-01

    BACKGROUND: Although epilepsy surgery is a recognized treatment option for drug-resistant epilepsies since several decades, the management of antiepileptic drugs (AEDs) after successful surgery still remains one of the most difficult and unsolved therapeutic challenges. Indeed, no systematic cont...

  15. The new generation of antiepileptic drugs: advantages and disadvantages.

    Science.gov (United States)

    Perucca, E

    1996-11-01

    1. After a hiatus of over 20 years, several new antiepileptic drugs (vigabatrin, lamotrigine, gabapentin, oxcarbazepine, topiramate, felbamate, zonisamide and tiagabine) have reached or approached the registration phase. 2. Compared with older agents, many new drugs exhibit simpler pharmacokinetics. This is especially true for vigabatrin and gabapentin, which are renally eliminated and have a low interaction potential. 3. Unlike most of the older agents, vigabatrin, lamotrigine, gabapentin and tiagabine are devoid of significant enzyme inducing or inhibiting properties. Topiramate, oxcarbazepine and felbamate may induce the metabolism of steroid oral contraceptives. In addition, felbamate also acts as a metabolic inhibitor. 4. To date, the efficacy of new drugs has been evaluated extensively only under add-on conditions in patients with partial seizures (with or without secondary generalization) refractory to conventional treatment. However, there is evidence that lamotrigine, zonisamide, felbamate and, possibly, topiramate may also be effective in generalized epilepsies. 5. In placebo-controlled studies, typically between 15 and 40% of patients with difficult-to-treat partial epilepsy have shown an improvement (defined as a 50% or greater decrease in seizure frequency) after addition of a new drug. Only a small minority of these patients achieved complete seizure control. 6. Compared with older agents, some of the new drugs may have a better tolerability profile. Felbamate, however, has been associated with a high risk of aplastic anaemia and hepatotoxicity. 7. At present, the main use of the new agents is in patients refractory to first-line drugs such as carbamazepine or valproate, and further studies are required to characterize their activity spectrum as well as their potential value in monotherapy. In most patients, new drugs cannot be recommended for first-line use until evidence is obtained that potential advantages in tolerability or ease of use outweigh

  16. Glucuronidation of antiepileptic drugs in women with epilepsy : on the role of age, steroid hormones and oral contraceptives

    NARCIS (Netherlands)

    Wegner, I.

    2013-01-01

    Epilepsy is a common neurological disorder with clinically important gender differences in both the expression and the impact of epilepsy. Understanding the complex interactions between sex hormones, epilepsy and antiepileptic drugs (AEDs) can greatly improve the care for women with epilepsy. This

  17. Antiepileptic drug poisoning: Three-year experience

    Directory of Open Access Journals (Sweden)

    Yahya Kemal Günaydın

    2015-01-01

    Conclusion: First generation antiepileptics are more toxic than SGAEs. In patients with serum carbamazepine level, particularly those over 30 mg/L, serious disorders of consciousness, cardiovascular toxicity, and metabolic disorders may occur. In VPA intoxication, there is a positive correlation between the serum VPA levels and ammonia levels. On account of this finding, one should be more careful about hyperammonemic hepatic encephalopathy as the serum VPA level rises.

  18. Epileptic seizure, as the first symptom of hypoparathyroidism in children, does not require antiepileptic drugs

    OpenAIRE

    Liu, Meng-Jia; Li, Jiu-Wei; Shi, Xiu-Yu; Hu, Lin-Yan; Zou, Li-Ping

    2016-01-01

    Objective Patients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism. Method This study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children. Result A total of 42 pa...

  19. Zebrafish embryotoxicity test for developmental (neuro)toxicity : Demo case of an integrated screening approach system using anti-epileptic drugs

    NARCIS (Netherlands)

    Beker van Woudenberg, Anna; Snel, Cor; Rijkmans, Eke; De Groot, Didima; Bouma, Marga; Hermsen, Sanne; Piersma, Aldert; Menke, Aswin; Wolterbeek, André

    2014-01-01

    To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

  20. Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs

    NARCIS (Netherlands)

    Beker van Woudenberg, A.; Snel, C.; Rijkmans, E.; Groot, D. de; Bouma, M.; Hermsen, S.; Piersma, A.; Menke, A.; Wolterbeek, A.

    2014-01-01

    To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

  1. Strategies for improving adherence to antiepileptic drug treatment in people with epilepsy.

    Science.gov (United States)

    Al-Aqeel, Sinaa; Gershuni, Olga; Al-Sabhan, Jawza; Hiligsmann, Mickael

    2017-02-03

    Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials and quasi-randomised controlled trials to assist people with adherence to antiepileptic medication. This is an updated version of the original Cochrane review published in the Cochrane Library, Issue 1, 2010. To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy. For the latest update, on 4 February 2016 we searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 4 February 2016), CINAHL Plus (EBSCOhost 1937 to 4 February 2016), PsycINFO (EBSCOhost 1887 to 4 February 2016), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We also searched the reference lists of relevant articles. Randomised and quasi-randomised controlled trials of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to the GRADE working group scale.The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate. We included 12 studies reporting data on 1642 participants (intervention = 833, control = 809). Eight studies targeted adults with epilepsy, one study included participants

  2. Seizure Recurrence in Children after Stopping Antiepileptic Medication: 5-Year Follow-Up

    Directory of Open Access Journals (Sweden)

    Inn-Chi Lee

    2017-08-01

    Conclusion: We found that a history of status epilepticus, symptomatic partial epilepsy, treatment duration before stopping antiepileptic drugs, and an abnormal EEG when the medication was stopped are important predictors of SR. The risk factors of SR after discontinuing antiepileptic drugs have been investigated in several studies. However, a history of status epilepticus as a predictive factor is rarely mentioned.

  3. The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

    Science.gov (United States)

    Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

    2017-09-01

    People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

  4. Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy.

    Science.gov (United States)

    Rohde, Natalie N; Baca, Christine B; Van Cott, Anne C; Parko, Karen L; Amuan, Megan E; Pugh, Mary Jo

    2015-05-01

    We examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities. From the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs. Among 256,284 IAVs, 2123 met inclusion criteria (mean age: 33years; 89% men). Seventy-two percent (n=1526) received monotherapy, most commonly valproate (N=425) and levetiracetam (n=347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N=45) were of reproductive age (≤45years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p<0.01). In this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing. Copyright © 2015. Published by Elsevier Inc.

  5. Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries.

    Science.gov (United States)

    Sasaki, Eita; Yokoi, Tsuyoshi

    2018-01-01

    Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

  6. Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

    Science.gov (United States)

    Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

    2014-01-01

    Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

  7. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  8. An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

    Science.gov (United States)

    Suraev, Anastasia S; Todd, Lisa; Bowen, Michael T; Allsop, David J; McGregor, Iain S; Ireland, Carol; Lintzeris, Nicholas

    2017-05-01

    Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A total of 976 responses met the inclusion criteria. Results show that 15% of adults with epilepsy and 13% of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after commencing cannabis products. The main reasons for medicinal cannabis use were to manage treatment-resistant epilepsy and to obtain a more favorable side-effect profile compared to standard antiepileptic drugs. The number of past antiepileptic drugs tried was a significant predictor of medicinal cannabis use in both adults and children with epilepsy. Fifty-six percent of adults with epilepsy and 62% of parents/guardians of children with epilepsy expressed willingness to participate in clinical trials of cannabinoids. This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Trends in Antiepileptic Drug Use in Children and Adolescents With Epilepsy.

    Science.gov (United States)

    Liu, Xinyue; Carney, Paul R; Bussing, Regina; Segal, Richard; Cottler, Linda B; Winterstein, Almut G

    2017-09-01

    We describe the trends in antiepileptic drug (AED) use in children and adolescents with epilepsy in the United States. We undertook a cross-sectional study based on Medicaid Analytic eXtract data set from 26 US states. Children and adolescents aged three to 18 years with at least one year continuous Medicaid fee-for-service coverage after the second outpatient or the first inpatient diagnosis of epilepsy in each calendar year during 1999 to 2009 were included in the study; therefore, 11 cohorts were established. A patient was defined as being exposed to a specific AED if he or she had at least one-day supply of the AED during the 1-year follow-up period. The annual prevalence of AEDs was reported, stratified by gender and age. The trends in AED use were evaluated through linear regression. The sample sizes of the 11 cohorts ranged between 17,304 and 22,672. The annual prevalence of valproic acid use declined from 42.4% in 1999 to 26.5% in 2009, and the prevalence of carbamazepine use declined from 37.1% to 10.2%. Meanwhile, the prevalence of levetiracetam use increased from 5.1% to about 32.0% in 2009, and the prevalence of oxcarbazepine use increased from 1.3% to 19.1%. Since 2008, levetiracetam (29.6%) has replaced valproic acid (27.8%) as the most commonly used AED in children and adolescents with epilepsy. The prevalence of diazepam use increased from 11.6% to 28.1%. Compared with first- and second-generation antiepileptic drugs, third-generation AEDs have fewer adverse side effects, resulting in increased patient treatment adherence. Equally important is the economic impact of these newer AEDs. This first-of-its-kind study underscores the need for large database studies that objectively assess the cost-effectiveness of third-generation AEDs versus first- and second-generation AEDs in the treatment of childhood epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Simultaneous HPLC-F analysis of three recent antiepileptic drugs in human plasma.

    Science.gov (United States)

    Mercolini, Laura; Mandrioli, Roberto; Amore, Mario; Raggi, Maria Augusta

    2010-09-21

    An original high-performance liquid chromatographic method with fluorescence detection is presented for the simultaneous determination of the three antiepileptic drugs gabapentin, vigabatrin and topiramate in human plasma. After pre-column derivatisation with dansyl chloride, the analytes were separated on a Hydro-RP column with a mobile phase composed of phosphate buffer (55%) and acetonitrile (45%) and detected at lambda(em)=500 nm, exciting at 300 nm. An original pre-treatment procedure on biological samples, based on solid-phase extraction with MCX cartridges for gabapentin and vigabatrin, and with Plexa cartridges for topiramate, gave high extraction yields (>91%), satisfactory precision (RSDvigabatrin and in the 1.0-50.0 microg mL(-1) range for topiramate, with limits of detection (LODs) between 0.1 and 0.3 microg mL(-1). After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. Accuracy results were satisfactory (recovery >91%). Therefore, the method seems to be suitable for the therapeutic drug monitoring (TDM) of patients treated with gabapentin, vigabatrin and topiramate. Copyright 2010 Elsevier B.V. All rights reserved.

  11. The Effect of Antiepileptic Drug of Lamotrigine, on the Function of Reproductive Hormones in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Khezri Motlagh

    2016-08-01

    Full Text Available Introduction: Lamotrigine is one of the never anti-epileptic drug. In this study the effects of lamotrigine have been observed on serum concentration of LH (Luteinizing hormone, FSH (Follicle-stimulating hormone, testosterone ,body and testis weight in male rat. Methods: The animal used in this experiment were 40 adult male rat from wistar race which were divided in to 5 group of 8.consisting of control group which received nothings, Sham group which received 0.2 ml distilled water via oral. Experimental group which received 100, 200, 400 mg/kg lamotrigine via oral after 14th day body weight were measured in all group and then the blood sample was taken from heart and concentration of LH.FSH, testosterone was measured. In addition the testis were separated and testis weight were measured in all group. Results: The result show that concentration of LH in experimental group did not show significant difference in compared with control group but in experimental group received 400mg/kg of lamotrigine  show a significant decrease in concentration of FSH and testosterone in comparison with control group .In addition lamotrigine had effect and testis weight in middle and high dose was reduce. Conclusion: Lamotrigine, an antiepileptic drug, reduced reproductive activity by inhibiting of hypothalamic-pituitary-gonadal axis in adult male rats.

  12. Antiepileptic drug use and the occurrence of pressure ulcers among bedridden institutionalized elderly patients: a retrospective chart review.

    Science.gov (United States)

    Arinzon, Zeev; Zeilig, Gabriel; Berner, Yitshal N; Adunsky, Abraham

    2005-09-01

    Phenytoin (PH) is indicated primarily for the control of grand mal and psychomotor seizures. However, topical PH has been used for the treatment of various types of ulcers, including pressure ulcers. The aim of this study was to investigate the possibility of a relationship between the use of oral PH and the prevalence of pressure ulcers among bedridden institutionalized elderly patients. This retrospective chart review was conducted in a state-run urban geriatric medical center in Israel and involved long-term bedridden institutionalized patients who were receiving chronic antiepileptic medication during the 7-year period between January 1996 and December 2003. The prevalence of pressure ulcers in patients who received treatment with PH alone or in combination with other antiepileptic drugs was compared with that in patients who received antiepileptic agents other than PH. The study analyzed data from the medical charts of 153 patients, 72 of whom received PH alone or in combination with other antiepileptic drugs, and 81 of whom received antiepileptic agents other than PH. Patients' mean (SD) age was 78.5 (7.2) years; 106 (69.3%) were women. All patients were totally dependent with respect to activities of daily living (mean Katz score, 2.0 [2.0]) and had severe cognitive decline (mean Mini-Mental State Examination score, 3.5 [3.3]). Pressure ulcers occurred in 9.7% of PH recipients and 27.2% of non-PH recipients (P = 0.006; chi2 = 7.55). In PH recipients, 85.7% of pressure ulcers were of mild to moderate severity (stage I or II), compared with 59.1% of ulcers in non-PH recipients; the difference between groups was not statistically significant. Four (18.2%) non-PH recipients and no PH recipients had stage IV pressure ulcers. In the PH group, 71.4% of patients had a pressure ulcer in only 1 anatomic location, compared with 22.7% of the non-PH group (P = 0.023; chi2 = 5.13); 28.6% of PH recipients and 63.6% of non-PH recipients had pressure ulcers in 2 or 3

  13. Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

    Science.gov (United States)

    Stephen, Linda J; Brodie, Martin J

    2018-01-01

    Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

  14. The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; de Jong-van den Berg, Lolkje T.W.

    2016-01-01

    BACKGROUND: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus. OBJECTIVES: We performed a literature review to find signals for potential associations between newer...... studies with pregnancies exposed to newer AEDs and detailed information on congenital anomalies. The congenital anomalies in the studies were classified according to the congenital anomaly subgroups of European Surveillance of Congenital Anomalies (EUROCAT). We compared the prevalence of specific...... and were not supported by other studies. No signals were found for the other newer AEDs, or the information was too limited to provide such a signal. CONCLUSION: In terms of associations between monotherapy with a newer AED in the first trimester of pregnancy and a specific congenital anomaly, the signals...

  15. Development Enamel Defects in Children Prenatally Exposed to Anti-Epileptic Drugs

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Endrup; Henriksen, Tine Brink; Haubek, Dorte

    2013-01-01

    Objective Some anti-epileptic drugs (AED) have well-known teratogenic effects. The aim of the present study was to elucidate the effect of prenatal exposure to AED and the risk of enamel defects in the primary and permanent dentition. Methods A total of 38 exposed and 129 non-exposed children, 6......–10 years of age, were recruited from the Aarhus Birth Cohort and the Department of Neurology, Viborg Regional Hospital, Denmark. Medication during pregnancy was confirmed by the Danish Prescription Database. All children had their teeth examined and outcomes in terms of enamel opacities and enamel...... hypoplasia were recorded. Results Children prenatally exposed to AED have an increased prevalence of enamel hypoplasia (11% vs. 4%, odds ratio (OR) = 3.6 [95% confidence interval (CI): 0.9 to 15.4]), diffuse opacities (18% vs. 7%, OR = 3.0; [95% CI: 1.0 to 8.7, p3) white opacities (18...

  16. Orientações ao pediatra sobre o manejo das drogas psicoativas e antiepilépticas Use of psychoactive and antiepileptic drugs: guidelines for pediatricians

    Directory of Open Access Journals (Sweden)

    Gibsi P. Rocha

    2004-04-01

    Full Text Available OBJETIVO: Revisar as indicações e o manejo clínico das drogas psicoativas e antiepilépticas na infância e adolescência. FONTES DE DADOS: Estudo baseado em revisão de literatura. Os autores organizam, de acordo com os quadros patológicos, uma rotina para o manejo dos psicofármacos e das drogas antiepilépticas na infância e na adolescência. SÍNTESE DOS DADOS: Indicação clínica, dosagem terapêutica e efeitos colaterais dos psicofármacos e drogas antiepilépticas são descritos. O uso de psicofármacos na infância e adolescência está se tornando mais freqüente, com a disponibilidade de novos medicamentos e com o crescimento do conhecimento sobre diagnóstico de transtornos emocionais nessa faixa etária. CONCLUSÕES: O manejo dos psicofármacos e drogas antiepilépticas na faixa etária pediátrica requer amplo conhecimento da farmacocinética dos mesmos, assim como de seus efeitos colaterais deletérios. A escolha do fármaco adequado é determinante no sucesso terapêutico.OBJECTIVE: To review the guidelines for the use of psychoactive and antiepileptic drugs in childhood and adolescence. SOURCES OF DATA: Literature review. SUMMARY OF THE FINDINGS: The clinical indications, dosage and side effects of psychoactive and antiepileptic drugs are presented. The use of psychoactive drugs is increasing due to the release of new drugs and to the better understanding of emotional disorders in children and adolescents. CONCLUSIONS: The use of antiepileptic and psychoactive drugs in childhood requires extensive knowledge concerning pharmacokinetics and deleterious side effects. An adequate choice of drugs is essential to ensure a successful treatment.

  17. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

    Directory of Open Access Journals (Sweden)

    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  18. The effect of antiepileptic drugs on the kidney function and structure.

    Science.gov (United States)

    Hamed, Sherifa Ahmed

    2017-09-01

    Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies. Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).

  19. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  20. An acardiac acephalic monster following in-utero anti-epileptic drug exposure.

    Science.gov (United States)

    Kutlay, B; Bayramoglu, S; Kutlar, A I; Yesildaglar, N

    1996-04-01

    Acardia, the absence of the heart, is one of the rarest medical anomalies. The exact mechanism which causes this anomaly is still unknown. The authors report the acardiac acephalic fetus of an epileptic mother who was on primidone therapy. The mother who received no antenatal care stopped taking primidone (her sole medication) in the third month of pregnancy with the fear of delivering a malformed baby and had three convulsions until delivery. This is the first reported case of acardia associated with anti-epileptic medication. The cause of the anomaly in this patient may be an unknown genetic defect, the maternal epileptic disorder, the convulsions, the anti-epileptic medication, or a combination of these factors.

  1. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  2. Alteration of the threshold stimulus for intraoperative brain mapping via use of antiepileptic medications

    Directory of Open Access Journals (Sweden)

    John W. Amburgy, MD

    2015-03-01

    Full Text Available Intraoperative seizures during awake craniotomy with cortical and subcortical mapping are a common occurrence. Patients are routinely treated preoperatively with anti-convulsive medications to reduce seizure occurrence. Historically these drugs have not been believed to significantly affect awake craniotomy procedures. We report a patient undergoing intraoperative mapping with differential response and seizure occurrence based upon antiepileptic drug usage. A 43 year old female presented with history of seizures, right sided hemiparesis, electrical sensations, and difficulty with language function. She was determined to have a mass lesion involving the left frontal and temporal lobes and subsequently elected to undergo resection by awake craniotomy with intraoperative mapping. A first attempt at lesion resection was performed after a missed dose of anti-convulsant medication (levetiracetam and was subsequently aborted because of repeated seizure activity. The threshold for seizure generation (1.75 mA was observed to be significantly lower than expected. Therapy was begun with both levetiracetam and phenytoin prior to a second attempted resection one week later. Thresholds for cortical motor response in the second operation were significantly higher than expected (> 9.0 mA, and no intraoperative seizure activity was observed. To our knowledge this is the first quantitative example of antiepileptic drugs affecting the current required for intraoperative mapping. This case highlights the potential for higher current requirements in patients preoperatively treated with high doses of antiepileptic drugs, as well as the importance of confirming adequate dosage of antiepileptic drugs in patients at an increased risk of seizure generation.

  3. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

  4. Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway.

    Science.gov (United States)

    Halvorsen, Kjell H; Johannessen Landmark, Cecilie; Granas, Anne Gerd

    2016-01-01

    Introduction. Antiepileptic drugs (AEDs) are used to treat different conditions in elderly patients and are among the drug classes most susceptible to be involved in drug-drug interactions (DDI). The aim of the study was to describe and compare use of AEDs between home care service and nursing home patients, as these patients are not included in nationwide databases of drug utilization. In the combined population, we investigate DDI of AEDs with other central nervous system- (CNS-) active drugs and DDIs involving AEDs in general. Materials and Methods. Point-prevalence study of Norwegian patients in home care services and nursing homes in 2009. At the patient level, we screened for different DDIs involving AEDs. Results. In total, 882 patients (7.8%) of 11,254 patients used AEDs and number of users did not differ between home care services and nursing homes (8.2% versus 7.7%). In the combined population, we identified 436 potential DDIs in 45% of the patients. Conclusions. In a large population of elderly, home care service and nursing home patients do not differ with respect to exposure of AEDs but use more AEDs as compared to the general population of similar age. The risk of DDIs with AEDs and other CNS-active drugs should be taken into consideration and individual clinical evaluations are assessed in this population.

  5. Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: A review.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Hofman, Paul A M; Vlooswijk, Marielle C G; Rouhl, Rob P W; de Louw, Anton J; Backes, Walter H; Jansen, Jacobus F A

    2015-12-01

    As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

    Full Text Available Objective. Patients with multiple sclerosis (MS are often suffering from neuropathic pain. Antiepileptic drugs (AEDs and tricyclic antidepressants (TCAs are commonly used and are susceptible to be involved in drug interactions. The aim of this retrospective study was to investigate the prevalence of use of antiepileptic and antidepressive drugs in MS patients and to discuss the theoretical potential for interactions. Methods. Review of the medical records from all patients treated at a dedicated MS rehabilitation centre in Norway between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation stay during the study period. Of these, 342 (31%; 249 females with mean age of 53 (±10 years and EDSS 4.8 (±1.7 used at least one AED (gabapentin 12.7%, pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6% or amitriptyline (9.7%. Polypharmacy was widespread (mean 5.4 drugs with 60% using additional CNS-active drugs with a propensity to be involved in interactions. Age, gender, and EDSS scores did not differ significantly between those using and not using AED/amitriptyline. Conclusion. One-third of MS patients attending a rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of polypharmacy and use of CNS-active drugs calls for awareness of especially pharmacodynamic interactions and possible excessive adverse effects.

  7. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-02

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  8. Comparative evaluation of oral hygiene status and gingival enlargement among epileptic and healthy children as related to various antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Neelam Hasmukhbhai Joshi

    2017-01-01

    Full Text Available Background: Epilepsy is a gathering of neurological disorders characterized by epileptic seizures. Epileptic children, who are on active treatment with antiepileptic drugs, have a well-recognized side effect of gingival enlargement. Therefore, all efforts should be made, particularly for the population who are diagnosed or affected by the systemic disease. This study was conducted with an aim to determine oral hygiene status and gingival enlargement among epileptic and healthy children as related to various antiepileptic drugs. Materials and Methods: The cross-sectional observational study was conducted in the department of pedodontics and attached general hospital. A sample size of 120 participants with 60 healthy and 60 epileptic children between age 2 and 14 years were included. Oral health status of participants was examined using oral hygiene simplified index and plaque index. Gingival enlargement was assessed using Miranda–Brunet index. For statistical analysis, one-way ANOVA test, independent t-test, and Pearson's Chi-square test were used. Results: From the total participants included in the study, 49% of participants had good oral hygiene from healthy group, and 28% participants had poor oral hygiene from the epileptic group. Sodium valproate was the most common drug used and was associated with increased gingival enlargement. Conclusion: Conclusion can be drawn that epileptic children under medication had poor oral hygiene and an increased risk for gingival enlargement as compared to their healthy counterparts. It must be stressed that the epileptic patients should be given dental care without conditions and provided with best possible care to restore esthetics and functions.

  9. Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

    Science.gov (United States)

    Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.

    2016-01-01

    Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267

  10. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis.

    Science.gov (United States)

    Jaques, Léonore; Rossetti, Andrea O

    2012-05-01

    Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy.

    Science.gov (United States)

    Bruun, Emmi; Virta, Lauri J; Kälviäinen, Reetta; Keränen, Tapani

    2017-08-01

    A study was conducted to investigate the frequency of potential pharmacokinetic drug-to-drug interactions in elderly patients with newly diagnosed epilepsy. We also investigated co-morbid conditions associated with epilepsy. From the register of Kuopio University Hospital (KUH) we identified community-dwelling patients aged 65 or above with newly diagnosed epilepsy and in whom use of the first individual antiepileptic drug (AED) began in 2000-2013 (n=529). Furthermore, register data of the Social Insurance Institution of Finland were used for assessing potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. We extracted all patients aged 65 or above who had received special reimbursement for the cost of AEDs prescribed on account of epilepsy in 2012 where their first AED was recorded in 2011-2012 as monotherapy (n=1081). Clinically relevant drug interactions (of class C or D) at the time of starting of the first AED, as assessed via the SFINX-PHARAO database, were analysed. Hypertension (67%), dyslipidemia (45%), and ischaemic stroke (32%) were the most common co-morbid conditions in the hospital cohort of patients. In these patients, excessive polypharmacy (more than 10 concomitant drugs) was identified in 27% of cases. Of the patients started on carbamazepine, 52 subjects (32%) had one class-C or class-D drug interaction and 51 (31%) had two or more C- or D-class interactions. Only 2% of the subjects started on valproate exhibited a class-C interaction. None of the subjects using oxcarbazepine displayed class-C or class-D interactions. Patients with 3-5 (OR 4.22; p=0.05) or over six (OR 8.86; p=0.003) other drugs were more likely to have C- or D-class interaction. The most common drugs with potential interactions with carbamazepine were dihydropyridine calcium-blockers, statins, warfarin, and psychotropic drugs. Elderly patients with newly diagnosed epilepsy are at high risk of clinically relevant pharmacokinetic

  12. Utilization of antiepileptic drugs during pregnancy: Comparative patterns in 38 countries based on data from the EURAP registry

    DEFF Research Database (Denmark)

    Battino, D.; Bonizzoni, E.; Craig, J.

    2009-01-01

    We assessed the utilization of antiepileptic drugs (AEDs), 1999-2005, in 4,798 prospective epilepsy pregnancies from 38 countries participating in EURAP, an international AED and pregnancy registry. Prominent differences in utilization patterns were observed across the various countries. Exposure...... to second-generation AEDs ranged from 3.5% in India and 7.3% in Italy to 75% in Denmark. Even wider variation was recorded in exposure to individual AEDs. The utilization of second-generation AEDs increased over time (for lamotrigine, from 9.9% of all pregnancies before 2001 to 29.6% after 2003......). The differences in use of individual AEDs across countries probably reflect lack of evidence concerning the optimal treatment of epilepsy in women of childbearing age, as well as variation in country-specific traditions, medication costs, and drug promotion. Our observations underscore the need for comparative...

  13. Fracture risk associated with use of antiepileptic drugs.

    Science.gov (United States)

    Vestergaard, Peter; Rejnmark, Lars; Mosekilde, Leif

    2004-11-01

    To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with decreased bone mineral density. The effects of newer AEDs are unknown. We undertook a population-based pharmacoepidemiologic case-control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls). All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine [CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10-1.26], [and oxcarbazepine (OXC; 1.14, 1.03-1.26)], clonazepam (CZP; 1.27, 1.15-1.41), phenobarbital (PB; 1.79, 1.64-1.95), and valproate (VPA; 1.15, 1.05-1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37-1.52), lamotrigine (1.04, 0.91-1.19), phenytoin (1.20, 1.00-1.43), primidone (1.18, 0.95-1.48), tiagabine (0.75, 0.40-1.41), topiramate (1.39, 0.99-1.96), and vigabatrin (0.93, 0.70-1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose-response relation. Fracture risk was more increased by liver-inducing AEDs (OR, 1.38; 95% CI, 1.31-1.45) than by noninducing AEDs (1.19; 95% CI, 1.11-1.27). A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power.

  14. Cross-National comparison of antiepileptic drug use: Catalonia, Denmark and Norway, 2007-2011

    Directory of Open Access Journals (Sweden)

    Pili Ferrer-Argeles

    2014-07-01

    Full Text Available Background: Antiepileptic drug  (AEDconsumption has increased in recent years mainly from those AEDs marketed since 1990. The purpose is to describe and compare AED consumption in Catalonia, Denmark and Norway.Methods: Population-based descriptive study set in the outpatient healthcare sector. Data were retrieved from the Norwegian Prescription Register, Danish Register of Medicinal Product Statistics and DATAMART® in Catalonia, for 2007-2011.We calculated defined daily doses/1000 inhabitants/day (DID, by age and gender. AEDs were defined according to the Anatomical Therapeutic Chemical classification (N03A. We reviewed the population covered by the databases, the drug data source and the definition of outpatient healthcare sector to compare the results across the three settings.Results: Total AED use steadily increased over the study period in the three settings. In 2011, consumption was highest in Catalonia (15.20 DID, followed by Denmark (15.06 DID and Norway (14.24 DID. The “other AEDs” (N03AX subgroup represented 60% of all AED use. The N03A pattern by gender did not differ across the three settings. Marked differences by age and gender appeared when studying lamotrigine, topiramate, gabapentin, pregabalin and levetiracetam.  Differences among the databases were mainly in the definition of outpatient healthcare setting.Conclusions: There was a rapid increase in “other AEDs” in all three settings. Although we did not have information on the indication for the use of AEDs, the drug data source, population coverage of the database and definition of the healthcare setting helped us interpret the results.

  15. Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?

    Science.gov (United States)

    Werner, Felix-Martin; Coveñas, Rafael

    2017-06-01

    Here, we describe in generalized epilepsies the alterations of classical neurotransmitters and neuropeptides acting at specific subreceptors. In order to consider a network context rather than one based on focal substrates and in order to make the interaction between neurotransmitters and neuropeptides and their specific subreceptors comprehensible, neural networks in the hippocampus, thalamus, and cerebral cortex are described. In this disease, a neurotransmitter imbalance between dopaminergic and serotonergic neurons and between presynaptic GABAergic neurons (hypoactivity) and glutaminergic neurons (hyperactivity) occurs. Consequently, combined GABA A agonists and NMDA antagonists could furthermore stabilize the neural networks in a multimodal pharmacotherapy. The antiepileptic effect and the mechanisms of action of conventional and recently developed antiepileptic drugs are reviewed. The GASH:Sal animal model can contribute to examine the efficacy of antiepileptic drugs. The issues of whether the interaction of classical neurotransmitters with other subreceptors (5-HT 7 , metabotropic 5 glutaminergic, A 2A adenosine, and alpha nicotinic 7 cholinergic receptors) or whether the administration of agonists/antagonists of neuropeptides might improve the therapeutic effect of antiepileptic drugs should be addressed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Algunas consideraciones en relación con los medicamentos antiepilépticos de nueva generación en los niños Some considerations in relation to the new generation antiepileptic drugs in children

    Directory of Open Access Journals (Sweden)

    Desiderio Pozo Lauzán

    2005-06-01

    Full Text Available El objetivo de este trabajo es revisar las principales drogas antiepilépticas de segunda generación y su administración en los niños: vigabatrina, felbamato, lamotrigina, topiramato, tiagabina, oxcarbazepina, zonisamida, levetiracetam y stiripentol. Al inicio se recomendaron en pacientes adultos con epilepsias focales refractarias, sin embargo desde hace varios años, se ha demostrado su eficacia en diferentes tipos de crisis en los niños. La lamotrigina y el topiramato se consideran medicamentos de amplio espectro. Se enfatiza en el metabolismo, vías de eliminación, indicaciones, dosis en los niños, interacciones medicamentosas y efectos colaterales de los medicamentos antiepilépticos de segunda generación. Se mencionan algunos de los nuevos medicamentos que actualmente están en investigación como antiepilépticos y que constituyen una tercera generaciónThe objective of this paper is to review the main second generation antiepileptic drugs and their administration in children: vigatrine, felbamate, lamotrigine, topiramate, tiagabine, oxcarbazepine, zonisamide, leventiracetam and stiripentol. At the beginning, they were recommended in adult patients with focal refractory epilepsies; however, their efficacy in different types of seizures in children has been proved for some years. Lamotrigine and topiramate are considered drugs of wide spectrum. Emphasis is made on metabolism, routes of elimination, indications, doses in children, drug interactions and side effects of the second generation antiepileptic drugs. Some of the new drugs that are currently under study as antiepileptic and that constitute a third generation, are mentioned.

  17. Comparative study of antiepileptic drug use during pregnancy over a period of 12 years in Spain. Efficacy of the newer antiepileptic drugs lamotrigine, levetiracetam, and oxcarbazepine.

    Science.gov (United States)

    Martinez Ferri, M; Peña Mayor, P; Perez López-Fraile, I; Escartin Siquier, A; Martin Moro, M; Forcadas Berdusan, M

    2018-03-01

    The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period. After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015) RESULTS: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV. The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV

  18. Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

    Science.gov (United States)

    Mula, Marco; von Oertzen, Tim J; Cock, Hannah R; Yogarajah, Mahinda; Lozsadi, Dora A; Agrawal, Niruj

    2017-07-01

    To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

    2017-09-01

    Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected Pbrand and generics for all three drugs of interest (Breslow-Day Pbrands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.

    Directory of Open Access Journals (Sweden)

    Rajput Muhammad Ali

    2013-01-01

    Full Text Available This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L. as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L., using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle, standard (diazepam and test (Trachyspermum ammi (L. extract. Trachyspermum ammi (L. demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L. and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L. showed antiepileptic activity, which may be due to the presence of thymol.

  1. Antiepileptic Medications in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Hirota, Tomoya; Veenstra-VanderWeele, Jeremy; Hollander, Eric; Kishi, Taro

    2014-01-01

    Electroencephalogram-recorded epileptiform activity is common in children with autism spectrum disorder (ASD), even without clinical seizures. A systematic literature search identified 7 randomized, placebo-controlled trials of antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate, and one each of lamotrigine,…

  2. The impact of the use of antiepileptic drugs on the growth of children

    Science.gov (United States)

    2013-01-01

    Background This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. Methods Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. Results One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. Conclusions These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA. PMID:24354857

  3. Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

    Science.gov (United States)

    Royaux, E; Van Ham, L; Broeckx, B J G; Van Soens, I; Gielen, I; Deforce, D; Bhatti, S F M

    2017-02-01

    Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

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    Krentz Hartmut B

    2010-06-01

    Full Text Available Abstract Background Anti-epileptic drugs (AEDs are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated. Methods HIV replication was analysed in proliferating human T cells during AED exposure. Patients receiving AEDs in a geographically-based HIV care program were assessed using clinical and laboratory variables in addition to assessing AED indication, type, and cumulative exposures. Results Valproate suppressed proliferation in vitro of both HIV-infected and uninfected T cells (p 0.05 but AED exposures did not affect HIV production in vitro. Among 1345 HIV/AIDS persons in active care between 2001 and 2007, 169 individuals were exposed to AEDs for the following indications: peripheral neuropathy/neuropathic pain (60%, seizure/epilepsy (24%, mood disorder (13% and movement disorder (2%. The most frequently prescribed AEDs were calcium channel blockers (gabapentin/pregabalin, followed by sodium channel blockers (phenytoin, carbamazepine, lamotrigine and valproate. In a nested cohort of 55 AED-treated patients receiving cART and aviremic, chronic exposure to sodium and calcium channel blocking AEDs was associated with increased CD4+ T cell levels (p 0.05 with no change in CD8+ T cell levels over 12 months from the beginning of AED therapy. Conclusions AEDs were prescribed for multiple indications without major adverse effects in this population but immune status in patients receiving sodium or calcium channel blocking drugs was improved.

  5. Anticataleptic and antiepileptic activity of ethanolic extract of leaves of Mucuna pruriens: A study on role of dopaminergic system in epilepsy in albino rats.

    Science.gov (United States)

    Champatisingh, D; Sahu, P K; Pal, A; Nanda, G S

    2011-04-01

    To assess the anticataleptic and antiepileptic activity of leaves of Mucuna pruriens in albino rats. Haloperidol-induced catalepsy (HIC), maximum electro-shock (MES) method, pilocarpine-induced Status epilepticus (PISE) and single-dose effect of M. pruriens were employed. M. pruriens (100 mg/kg) had significant anticataleptic and antiepileptic activity in HIC, MES, and PISE. M. pruriens extract has the potential to be an anticataleptic and antiepileptic drug. Dopamine and 5-HT may have a role in such activity.

  6. Current status of the New Antiepileptic drugs in chronic pain.

    Directory of Open Access Journals (Sweden)

    Harpreet Singh Sidhu

    2016-08-01

    Full Text Available Antiepileptic drugs (AEDs are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various Non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder

  7. Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

    Science.gov (United States)

    Habib, Mansur; Khan, Sharif Uddin; Hoque, Azhahul; Mondal, Badrul Alam; Hasan, A T M Hasibul; Chowdhury, Rajib Nayan; Haque, Badrul; Rahman, Kazi Mohibur; Chowdhury, Ahmed Hossain; Ghose, Swapon Kumar; Mohammad, Quazi Deen

    2013-11-18

    Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a

  8. Use of antiepileptic drugs and risk of falls in old age: A systematic review.

    Science.gov (United States)

    Haasum, Ylva; Johnell, Kristina

    2017-12-01

    The aim of this study is to systematically review the scientific literature to investigate if use of antiepileptic drugs (AEDs) is associated with falls and/or recurrent falls in old age. We searched the literature for relevant articles in PubMed and Embase published up until 3rd December 2015. Studies on people aged 60 years and over with an observational design assessing the risk of fall in people exposed to AEDs compared to people not exposed to AED were included. We found 744 studies by searching Medline and Embase and an additional 9 studies by reviewing relevant reference lists. Of these studies, 13 fulfilled our predefined criteria. The articles were of various study design, sizes and follow-up times, and presented the results in different ways. Also, confounder adjustment varied considerably between the studies. Ten studies presented results for the association between use of any AED and any fall/injurious fall. Of these studies, 6 presented adjusted estimates, of which all but one showed statistically significant associations between use of any AED and any fall/injurious fall. Six studies investigated the association between use of any AED and recurrent falls. Of these, only 3 studies presented adjusted effect estimates of which 2 reached statistical significance for the association between use of AEDs and recurrent falls in elderly people. Our results indicate an association between use of AEDs and risk of falls and recurrent falls in older people. This finding may be clinically important given that a substantial amount of older people use these drugs. However, further research is needed to increase the knowledge about the actual risk of falls when using these drugs in old age. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Improving clinical drug development regulatory procedures for anticonvulsants

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2015-01-01

    Full Text Available Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the noninferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

  10. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

    Science.gov (United States)

    Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

    2017-12-15

    Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary

  11. The Teratogenic Effects of Antiepileptic Drug, Topiramate, on the Development of Chick Embryos

    Directory of Open Access Journals (Sweden)

    Jantima Roongruangchai

    2017-05-01

    Full Text Available Background: Anti-epileptic drugs are known to be the risk of teratogenicity. Topiramate (TPM is a new kind of such drug, for which no research has confirmed the incidence of producing congenital abnormalities. Objective: This study was conducted to study the teratogenic effects of TPM by using chick embryos as an animal model and the results can be compared to the human embryo of the same stage. Methods: Fertilized Leghorn hen eggs were injected in ovo with two concentrations of TPM, which were 10mg, and 20mg, in NSS at a volume of 0.1 ml into the yolk sac at 21 hrs of incubation and repeated injections at 72 hrs at a volume of 0.05 ml. The chick embryos on day 3, 6 and 11 of incubation were sacrificed and all living embryos were processed for total mount and serial section. Results: The mortality rate increased corresponding to the concentrations of TPM, and the embryonic stage. The total mount of day 3 showed major abnormalities of the eye and heart, such as microphthalmia and looser of heart looping. The serial section of day 3 showed opening of the anterior neuropore, ectopia viscerae and multiple malformations of the eye and heart. Day 6 chick embryos showed ectopia cordis and ectopia viscerae. Moreover, there were retardation and abnormalities of several organs such as eye, heart, liver, mesonephros and gonads. Day 11 chick embryos showed ectopia viscerae and several growth retardations, retardation of ossification of both limb bones and skull bones. Conclusion: This study showed that TPM might cause embryonic death, growth retardation and abnormalities of the eye, heart, an opening of the anterior neuropore and ectopia viscerae. This might indicate abnormalities to the baby born from mother with gestational epilepsy who was taking this drug continuously, and it might lead to spontaneous abortion or congenital anomalies of the fetus.

  12. [Consensus clinical practice guidelines of the Andalusian Epilepsy Society on prescribing generic antiepileptic drugs].

    Science.gov (United States)

    Cañadillas-Hidalgo, F M; Sánchez-Alvarez, J C; Serrano-Castro, P J; Mercadé-Cerdá, J M

    Pharmaceutical spending in Spain accounts for 1.2-1.4% of the gross domestic product and is increasing by 5-12% per year. One of the measures adopted by the government to cut this spending is the possible substitution of original prescribed drugs by generics. In the case of antiepileptic drugs (AED), which are characterised by a scant therapeutic margin, these steps have sparked a scientific debate about their repercussion on the control of epileptic patients. We propose to draw up a set of implicit evidence-based consensus practice guidelines concerning issues related with this topic. A selective search for quality scientific information on the subject was conducted on PubMed-Medline, Tripdatabase and the Biblioteca Cochrane Plus. The selected references were analysed and discussed by the authors, and the recommendations deriving from them were collected. A total of 21 primary documents and 16 practice guidelines, protocols or experts' recommendations were identified. Our recommendations were explicitly included at the end of the text. The Andalusian Epilepsy Society makes the following recommendations: 1) not replacing an innovative AED by its generic in a controlled patient; 2) beginning treatment with a generic AED in monotherapy or in association is acceptable; 3) not exchanging generic AED from different pharmaceutical companies; 4) explaining to the patient the rules governing the authorization of generics and the importance of avoiding exchanges between different generic AED; and 5) if there is some worsening of the clinical condition or side effects appear following the introduction of a generic, the causes must be investigated and communicated to the bodies responsible for pharmacovigilance.

  13. The evaluation of 25-hydroxy vitamin D, calcium, phosphate and alkaline phosphatase levels in epileptic children under antiepileptic medication

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    Keyhani doost Z

    2011-01-01

    Full Text Available "n 800x600 Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} Background: Epilepsy is a common disease in the pediatric neurology. There are frequent anti-epileptic drugs which are used in management of epilepsy. Anti-epileptic drugs may have some complications on bone and vitamin-D metabolism. In this study we aimed to evaluate vitamin-D metabolism in epileptic children."n"nMethods: The study was a prospective and cross sectional one. A total 89 epileptic children who were taking anti-epileptic drugs for longer than six months with no underlying disorder in Imam Khomeini and Bahrami Hospitals in Tehran, Iran were enrolled in our study"n"nResults: Forty nine boys and 40 girls were enrolled in this study; mean age of the patients was 7.8±2.1 years. Mean duration of anti-epileptic drug therapy was 2.3 years (SD=0.4, 70 of patients were under monotherapy and 19 were under polytherapy. None of the patients had signs of rickets. Serum calcium and phosphor levels were within normal ranges. Serum alkaline phosphates levels were increased more than two times in 43%. 42% had vitamin-D deficiency (25-OH Vit D<10 ng/ml and another 33% had vitamin-D insufficiency (10<25-oh Vit D<20 ng/ml. 29 patients (32% were taking prophylactic supplemental Vit D (200-400 IU/day. There was significant difference between patients taking supplemental vitamin-D as prophylaxis and patients who did not (p=0.04. There was no significant difference in vitamin-D levels between patients according to age, gender or different drugs."n"nConclusion: Periodic

  14. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

  15. Antiepileptic drugs during pregnancy in primary care: a UK population based study.

    Directory of Open Access Journals (Sweden)

    Shuk-Li Man

    Full Text Available Antiepileptic drugs (AEDs are commonly prescribed for epilepsy and bipolar disorder but little is known about their use in pregnancy. We examined secular trends in AED prescribing in pregnancy and pregnancy as a determinant for stopping AED prescribing.We identified 174,055 pregnancies from The Health Improvement Network UK primary care database. Secular trends in AED prescribing during pregnancy were examined between 1994 and 2009. We used Cox's regression analyses to compare time to discontinuation of AED prescriptions between pregnant and non-pregnant women and to identify predictors of discontinuation of AEDs in pregnancy.Prescribing of carbamazepine and sodium valproate have declined since 1994 despite being the most commonly prescribed AEDs in pregnancy up to 2004. Prescribing of lamotrigine in pregnancy has steadily increased and has been the most popular AED prescribed in pregnancy since 2004. Pregnant women with epilepsy were twice as likely to stop receiving AEDs (Hazard Ratio (HR 2.00, 95% Confidence Interval (CI 1.62-2.47 when compared to non-pregnant women and for women with bipolar disorder this was even higher (HR 3.07, 95% CI 2.04-4.62. For pregnant women with epilepsy, those receiving AEDs less regularly before pregnancy were more likely to stop receiving AEDs in pregnancy.Lamotrigine has been increasingly prescribed in pregnancy over older AEDs namely carbamazepine and sodium valproate. Pregnancy is a strong determinant for the discontinuation of AED prescribing particularly for women with bipolar disorder.

  16. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Devarbhavi, Harshad; Andrade, Raúl J

    2014-05-01

    Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Common allergies do not influence the prevalence of cutaneous hypersensitivity reactions to antiepileptic drugs.

    Science.gov (United States)

    Bosak, Magdalena; Porębski, Grzegorz; Słowik, Agnieszka; Turaj, Wojciech

    2017-09-01

    The aim of the study was to establish whether the presence of common allergies increases the risk of drug-related hypersensitivity reactions among patients with epilepsy treated with antiepileptic drugs (AEDs). We studied 753 patients with epilepsy seen in tertiary outpatient epilepsy clinic. We obtained data related to epilepsy type, past and ongoing treatment with AEDs, occurrence of maculopapular exanthema or more serious cutaneous adverse reactions (Stevens-Johnson syndrome - SJS) and their characteristics. We noted an occurrence of allergic reactions unrelated to treatment with AED, including rash unrelated to AED, bronchial asthma, persistent or seasonal allergic rhinitis, atopic dermatitis, rash after specific food and other allergic reactions. There were 61 cases of AED-related cutaneous hypersensitivity reaction (including 3 cases of SJS) noted in association with 2319 exposures to AEDs (2.63%) among 55 out of 753 patients (7.3%). Cutaneous hypersensitivity reaction to AED was most commonly noted after lamotrigine (12.1%), carbamazepine (5.4%) and oxcarbazepine (4.1%). Prevalence of allergic reactions unrelated to AED was similar between patients with and without AED-related cutaneous hypersensitivity reaction (rash unrelated to AED: 16.4% vs. 10.2%; bronchial asthma: 1.8% vs. 0.1%; persistent allergic rhinitis: 7.3% vs. 10.2%; seasonal allergic rhinitis: 7.3% vs. 11.7%; atopic dermatitis: 0 vs. 0.7%; rash after specific food: 5.4% vs. 6.4%; other allergic reactions: 5.4% vs. 5.2%, respectively; P>0.1 for each difference). Presence of common allergies is not a significant risk factor for AED-related cutaneous hypersensitivity reaction among patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Androsova, Ganna; Krause, Roland; Borghei, Mojgansadat; Wassenaar, Merel; Auce, Pauls; Avbersek, Andreja; Becker, Felicitas; Berghuis, Bianca; Campbell, Ellen; Coppola, Antonietta; Francis, Ben; Wolking, Stefan; Cavalleri, Gianpiero L; Craig, John; Delanty, Norman; Koeleman, Bobby P C; Kunz, Wolfram S; Lerche, Holger; Marson, Anthony G; Sander, Josemir W; Sills, Graeme J; Striano, Pasquale; Zara, Federico; Sisodiya, Sanjay M; Depondt, Chantal

    2017-10-01

    Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  19. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  20. VNS Therapy versus the latest antiepileptic drug.

    Science.gov (United States)

    Ben-Menachem, Elinor; French, Jacqueline A

    2005-09-01

    Pro AED: The central issue in medical decision-making is risk-benefit assessment. Surgery of any type is still considered to be a major undertaking. To warrant these risks, the patient has a right to expect that they have a greater chance of a good outcome with an invasive therapy than with a non-invasive one. The main question is when, if ever, this becomes the case when comparing implantation of a VNS Therapy System versus adding an antiepileptic drug (AED)? After the first drug? The second? After all AEDs have failed? To date, no randomized trial comparing the addition of an AED against vagus nerve stimulation (VNS Therapy) has been undertaken, although several are currently being contemplated. Without this information, it is more difficult to make a case for early implementation of VNS Therapy. Unfortunately, few data are available regarding the potential for patients to become seizure-free after implantation of a VNS Therapy System. Another issue is side effects. It is important to remember that VNS Therapy also produces adverse events, albeit very different in character than those associated with AEDs, to which physicians have become accustomed. These include cough, dyspnea, pharyngitis, voice alteration and sleep apnea. A less frequently discussed, potentially negative consequence of VNS Therapy relates to the ability to obtain imaging of the patient. Patients who have undergone VNS Therapy System implantation are not candidates for imaging of the chest, breast, or abdomen. A second issue is that imaging of the brain can only be performed with MRI scanners that meet certain requirements, and as MRI technology develops, scanners meeting these requirements may become harder to find. However, to summarize, VNS Therapy is an excellent and useful treatment choice. Fortunately, the choice between AEDs and VNS Therapy is not an "either/or" decision. Each has a role in the treatment of patients with epilepsy, and the advantages and disadvantages of each should be

  1. The reasons for the epilepsy treatment gap in Kilifi, Kenya: using formative research to identify interventions to improve adherence to antiepileptic drugs.

    Science.gov (United States)

    Carter, Julie A; Molyneux, Catherine S; Mbuba, Caroline K; Jenkins, Jo; Newton, Charles R J C; Hartley, Sally D

    2012-12-01

    Many people with epilepsy (PWE) in resource-poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

    Science.gov (United States)

    Müller, A; Helbig, I; Jansen, C; Bast, T; Guerrini, R; Jähn, J; Muhle, H; Auvin, S; Korenke, G C; Philip, S; Keimer, R; Striano, P; Wolf, N I; Püst, B; Thiels, Ch; Fogarasi, A; Waltz, S; Kurlemann, G; Kovacevic-Preradovic, T; Ceulemans, B; Schmitt, B; Philippi, H; Tarquinio, D; Buerki, S; von Stülpnagel, C; Kluger, G

    2016-01-01

    Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation. Copyright © 2015. Published by Elsevier Ltd.

  3. Recent Advances in Antiepileptic Herbal Medicine.

    Science.gov (United States)

    Manchishi, Stephen M

    2018-01-01

    Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. The limited supply, high cost as well as low efficacy and adverse side effects of antiepileptic drugs (AEDs) is a matter of major concern. Herbal medicine has always been traditionally part of treatment of epilepsy. Herbal medicines are generally well tolerated, with fewer side effects. To highlight some herbal extracts that have been studied for their anticonvulsant activity in animal models, literature search from PubMed and Science Direct, was performed. The keywords for the search consisted of combinations of the following terms: Herbal antiepileptic and/or anticonvulsant, botanicals + epilepsy. Literature published in the last five years was considered. Eighteen (18) anticonvulsant herbal agents are reported and discussed. Experiments mostly consisted of phenotypic screens in rodents, with little diversity in screening methods. In most experiments, the tested extracts prolonged the time to onset of seizures and decreased their duration. Most experimenters implicate potentiation of GABAergic activity as the mode of action of the extracts, even though some experimenters did not fully characterise the bioactive chemical composition of their extracts. Potential herbal remedies have shown positive results in animal models. It remains unclear how many make it into clinical trials and eventually making part of the AED list. More rigorous research, applying strict research methodology with uniform herbal combinations, as well as clinical studies are urgently needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

    Science.gov (United States)

    Gao, Yanqiong; Yan, Hua; Jin, Ruirui; Lei, Peng

    2016-11-01

    Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

  5. [Antiepileptic drugs in the control of the impulses disorders].

    Science.gov (United States)

    Roncero, C; Rodríguez-Urrutia, A; Grau-López, L; Casas, M

    2009-01-01

    The disorders classified as control of the impulses; explosive intermittent disorder, pathological gambling, kleptomania, pyromania, pathological gambling, hair pullers, compulsive purchases, skin picking and onychophagia are a heterogeneous set of clinical entities, most of them with little prevalence. Nevertheless, they cause important personal and social dysfunctions and present great comorbidity with other psychiatric disorders. Antipsychotics, antidepressive agents, serotoninergic agonists, naltrexone, beta blockers antiandrogen, lithium and anticonvulsants have been used in their pharmacological treatment. Currently, interest is growing on the use of the antiepileptics because their possible usefulness has been described in these disorders. However, the neurobiological effects are only partially known in some cases. We have reviewed the literature regarding the treatment of these disorders with mood stabilizers, (lithium, carbamazepine, valproate, phenitoin, oxcarbacepin, topiramate, lamotrigin, leviteracetam) and have described those studies on which the current knowledge and evidence are based. The results must be considered as provisional and must be updated in the future, since they are mostly based on case reports, case series or opened clinical trials, their being little knowledge based on double blind clinical trials.

  6. Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.

    Science.gov (United States)

    van Veenendaal, Tamar M; IJff, Dominique M; Aldenkamp, Albert P; Lazeron, Richard H C; Hofman, Paul A M; de Louw, Anton J A; Backes, Walter H; Jansen, Jacobus F A

    2017-06-28

    To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant ( P effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed. Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

  7. The Use of Antiepileptic Drugs (AEDs for the Treatment of Pediatric Aggression and Mood Disorders

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    Joseph Gonzalez-Heydrich

    2010-09-01

    Full Text Available Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs – valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine – in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

  8. The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders.

    Science.gov (United States)

    Munshi, Kaizad R; Oken, Tanya; Guild, Danielle J; Trivedi, Harsh K; Wang, Betty C; Ducharme, Peter; Gonzalez-Heydrich, Joseph

    2010-09-10

    Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs - valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine - in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

  9. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

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    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  10. Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats

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    Yeshwant Singh

    2014-01-01

    Full Text Available Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs on an antimalarial candidate 99/411 pharmacokinetic (PK profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT, Carbamazepine (CBZ, and Gabapentin (GB in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data.

  11. Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

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    Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

    2011-10-01

    4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Applying a perceptions and practicalities approach to understanding nonadherence to antiepileptic drugs.

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    Chapman, Sarah C E; Horne, Rob; Eade, Rona; Balestrini, Simona; Rush, Jennifer; Sisodiya, Sanjay M

    2015-09-01

    Nonadherence to antiepileptic drugs (AEDs) is a common cause of poor seizure control. This study examines whether reported adherence to AEDs is related to variables identified in the National Institute for Health and Clinical Excellence (NICE) Medicines Adherence Guidelines as being important to adherence: perceptual factors (AED necessity beliefs and concerns), practical factors (limitations in capability and resources), and perceptions of involvement in treatment decisions. This was a cross-sectional study of people with epilepsy receiving AEDs. Participants completed an online survey hosted by the Epilepsy Society (n = 1,010), or as an audit during inpatient admission (n = 118). Validated questionnaires, adapted for epilepsy, assessed reported adherence to AEDs (Medication Adherence Report Scale [MARS]), perceptions of AEDs (Beliefs about Medicines Questionnaire [BMQ]), and patient perceptions of involvement in treatment decisions (Treatment Empowerment Scale [TES]). Low adherence was related to AED beliefs (doubts about necessity: t(577) = 3.90, p < 0.001; and concerns: t(995) = 3.45, p = 0.001), reported limitations in capability and resources (t(589) = 7.78, p < 0.001), and to perceptions of a lack of involvement in treatment decisions (t(623) = 4.48, p < 0.001). In multiple logistic regression analyses, these factors significantly (p < 0.001) increased variance in reported adherence, above that which could be explained by age and clinical variables (seizure frequency, type, epilepsy duration, number of AEDs prescribed). Variables identified in the NICE Medicines Adherence Guidelines as potentially important factors for adherence were found to be related to adherence to AEDs. These factors are potentially modifiable. Interventions to support optimal adherence to AEDs should be tailored to address doubts about AED necessity and concerns about harm, and to overcome practical difficulties, while engaging patients in treatment decisions. Wiley Periodicals, Inc.

  13. Uncertainties from a worldwide survey on antiepileptic drug withdrawal after seizure remission.

    Science.gov (United States)

    Bartolini, Luca; Majidi, Shahram; Koubeissi, Mohamad Z

    2018-04-01

    We sought to determine differences in practice for discontinuation of antiepileptic drugs (AEDs) after seizure remission and stimulate the planning and conduction of withdrawal trials. We utilized a worldwide electronic survey that included questions about AED discontinuation for 3 paradigmatic cases in remission: (1) focal epilepsy of unknown etiology, (2) temporal lobe epilepsy after surgery, and (3) juvenile myoclonic epilepsy. We analyzed 466 complete questionnaires from 53 countries, including the United States. Statistical analysis included χ 2 and multivariate logistic regression. Case 1: responders in practice for <10 years were less likely to taper AEDs: odds ratio (OR) (95% confidence interval [CI]) 0.52 (0.32-0.85), p = 0.02. The likelihood of stopping AEDs was higher among doctors treating children: OR (95% CI): 11.41 (2.51-40.13), p = 0.002. Doctors treating children were also more likely to stop after 2 years or less of remission: OR (95% CI): 6.91 (2.62-19.31), p = 0.002, and the same was observed for US physicians: OR (95% CI): 1.61 (1.01-2.57), p = 0.0049. Case 2: responders treating children were more likely to taper after 1 year or less of postoperative remission, with the goal of discontinuing all medications: OR (95% CI): 1.91 (1.09-3.12), p = 0.015, and so were US-based responders: OR (95% CI): 1.73 (1.21-2.41), p = 0.003. Case 3: epileptologists were less likely to withdraw the medication: OR (95% CI): 0.56 (0.39-0.82), p = 0.003, and so were those in practice for 10 or more years: OR (95% CI): 0.54 (0.31-0.95), p = 0.025. We observed several differences in practice for AED withdrawal after seizure remission that highlight global uncertainty. Trials of AED discontinuation are needed to provide evidence-based guidance.

  14. Mapping the availability, price, and affordability of antiepileptic drugs in 46 countries.

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    Cameron, Alexandra; Bansal, Amit; Dua, Tarun; Hill, Suzanne R; Moshe, Solomon L; Mantel-Teeuwisse, Aukje K; Saxena, Shekhar

    2012-06-01

    In low- and middle-income countries (LMICs), a large proportion of people with epilepsy do not receive treatment. An analysis of the availability, price, and affordability of antiepileptic drugs (AEDs) was conducted to evaluate whether these factors contribute to the treatment gap. Data for five AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, and diazepam) were obtained from facility-based surveys conducted in 46 countries using the World Health Organization/Health Action International (WHO/HAI) methodology. Outcome measures were percentage availability, ratios of local prices to international reference prices, and number of days' wages needed by the lowest-paid unskilled government worker to purchase treatment. Prices were adjusted for inflation/deflation and purchasing power parity. The average availability of generic AEDs in the public sector was Private sector availability of generic oral AEDs ranged from 42.2% for phenytoin to 69.6% for phenobarbital. Public sector patient prices for generic carbamazepine and phenytoin were 4.95 and 17.50 times higher than international reference prices, respectively, whereas private sector patient prices were 11.27 and 24.77 times higher, respectively. For both medicines, originator brand prices were about 30 times higher. The highest prices were observed in the lowest income countries. The lowest-paid government worker would need wages from 1-2.6 days' to purchase a month's supply of phenytoin, whereas carbamazepine would cost 2.7-16.2 days' wages. Despite its widespread use in LMICs, WHO/HAI survey data for phenobarbital was only available from a small number of countries. In LMICs, availability and affordability of AEDs are poor and may be acting as a barrier to accessing treatment for epilepsy. Ensuring a consistent supply of AEDs at an affordable price should be a priority. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  15. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies

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    Ekta Arora

    2016-01-01

    Full Text Available Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically. The main effects include hypocalcemia, hypophosphatemia, reduced serum levels of Vitamin D, increase in parathormone (PTH levels, and alterations in bone turnover markers. The CYP450 enzyme-inducing AEDs such as phenytoin, phenobarbital, carbamazepine, and primidone are the most common AEDs associated with bone disorders while the data regarding the effect of valproate and newer AEDs such as lamotrigine, gabapentin, vigabatrin, levetiracetam, and topiramate on bone metabolism and bone density are scanty and controversial. Deficiency of Vitamin D is commonly described as a cause for the bone loss in epileptic patients while others being decreased absorption of calcium, increased PTH levels, and inhibition of calcitonin secretion, etc. However, there are no formal practical guidelines for the management of bone disease among those taking AEDs. Evidence-based strategies regarding monitoring, prevention, and treatment of bone diseases in patients on AED therapy are needed.

  16. Women with epilepsy in childbearing age: Pregnancy-related knowledge, information sources, and antiepileptic drugs.

    Science.gov (United States)

    Friedrich, Latica; Sruk, Ana; Bielen, Ivan

    2018-03-01

    Pregnancy-related issues in epilepsy (PRIE) are essential for management of epilepsy in women. We conducted a study among women with epilepsy (WWE) aged 15-45years about their knowledge, sources, and needs for information regarding PRIE, which included their current antiepileptic drugs (AEDs) usage. Women with epilepsy, visitors of Croatian Association for Epilepsy webpage, were offered an online questionnaire, and 200 responses were analyzed. The mean number of correct answers about PRIE was 3.5 out of 5. Main predictors of knowledge on PRIE were a prior consultation with a neurologist and higher usage of books/brochures. A prior neurologist consultation on PRIE was stated by 45% of subjects. As the preferred future mode of being informed on PRIE, majority of women (61%) chooses their neurologist, 22% written materials distributed by a neurologist, and only 13% Internet. Levetiracetam was the most commonly used AED (34.5%). Valproate was used by 26%, and of those 59% stated no previous consultation on PRIE with their neurologist. In summary, we believe our study shows that knowledge of PRIE among WWE in their childbearing age is unsatisfactory, as are the neurologist consultation rates about PRIE. Our results demonstrate that, despite modern technologies, educational activities should be based on neurologist consultations and providing the patients with appropriate written materials. This is especially true for the relatively large proportion of women still taking valproate. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Role of reflexology and antiepileptic drugs in managing intractable epilepsy--a randomized controlled trial.

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    Dalal, Krishna; Devarajan, Elanchezhiyan; Pandey, Ravindra Mohan; Subbiah, Vivekanandan; Tripathi, Manjari

    2013-01-01

    This report is based on the results of a randomized parallel controlled trial conducted to determine the efficacy of reflexology therapy in managing intractable epilepsy. Subjects who failed epilepsy surgery or were not candidates for epilepsy surgery or were non-responders of antiepileptic drugs (AEDs) took part in this study. The trial was completed by 77 subjects randomly assigned to 2 arms: control (AEDs) and reflexology (AEDs + reflexology therapy). The hypothesis was that hand reflexology therapy could produce results similar to those of vagus nerve stimulation, and foot reflexology therapy could maintain homeostasis in the functional status of individual body parts. Reflexology therapy was applied by family members. The follow-up period was 1.5 years. Quality of life in epilepsy patients was assessed with the QOLIE-31 instrument. In the reflexology group, the median baseline seizure frequency decreased from 9.5 (range 2-120) to 2 (range 0-110) with statistical significance (p reflexology group were 41.05 ± 7 and 43.6 ± 8, respectively. Posttherapy data were 49.07 ± 6 and 65.4 ± 9, respectively (p reflexology method allowed detection of knee pain in 85% of the reflexology group patients (p reflexology group patients reported nausea/vomiting (n = 1), change in voice (n = 2), and hoarseness (n = 1). Reflexology therapy together with AEDs may help reducing seizure frequency and improving quality of life in individuals with epilepsy. Copyright © 2013 S. Karger AG, Basel.

  18. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: Vigabatrin

    Science.gov (United States)

    Edwin, Bismi; Joe, I. Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the Csbnd C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system.

  19. Off-label use analysis of novel antiepileptic drugs in Sichuan area: a multicenter survey in pediatric patients

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    CAI Qian-yun

    2012-10-01

    Full Text Available Objective To investigate current status and safety about off-label use of levetiracetam, topiramate, oxcarbazepine, lamotrigine among pediatric patients in Sichuan area, so as to provide baseline data for formulating guidelines of off-label drug use. Methods Medical records of pediatric epileptic patients receiving antiepileptic drugs (AEDs from July 2010 to November 2011 were collected at the following hospitals: West China Second University Hospital of Sichuan University, Chengdu Women's and Children's Central Hospital and Sichuan Provincial People's Hospital. The numbers of patients receiving AEDs and novel AEDs were calculated. Off-label drug use and the category of off-label drug use were judged according to the indications listed in drug instructions. The incidence of off-label drug use was calculated. The patients receiving novel AEDs were devided into on-label and off-label use groups; the clinical characteristics of these two groups were summarized and adverse reactions of two groups were compared by using χ2 test. Results During the study period, there were totally 854 patients receiving AEDs including 670 patients receiving novel AEDs. Among 670 patients 406 patients off-label use group received off-label use of novel AEDs, accounting for 47.54% (406/854 of the total patients receiving AEDs and 60.60% (406/670 of patients receiving novel AEDs. When compared with on-label use group, off-label use group had more younger patients, more patients with single-drug use and more patients with generalized epilepsy or epileptic syndrome. The rates of off-label using drug were levetiracetam 78.50% (157/200, topiramate 79.81% (253/317, oxcarbazepine 21.32% (42/197 and lamotrigine 33.33% (21/63. The off-label use of levetiracetam and topiramate occured in all three aspects: age, single-drug use and seizure type. The adverse reaction rates of off-label use were oxcarbazepine 16.67% (7/42, topiramate 14.81% (36/243, levetiracetam 10.60% (16

  20. Definition of rational antiepileptic polypharmacy.

    Science.gov (United States)

    Wilder, B J; Homan, R W

    1996-01-01

    Rational polypharmacy is in its earliest stages of development and will require substantial additional development to realize its full potential. Indeed, despite the powerful appeal of the concept, clinical proof is not yet available that RP is superior to monotherapy. Important questions need to be addressed: 1. Will RP control seizures more effectively than monotherapy? 2. What data are needed to develop RP for a specific patient? 3. Will RP be cost effective? 4. Can RP be developed which will treat or prevent epilepsy while controlling seizures? Possible approaches to these questions could include: 1. The development of a data base for prospective use to monitor patients being treated at Epilepsy Centers using RP principles. 2. Use the data obtained from the above to construct more specific studies to compare identified combination therapies with monotherapy. 3. Prospectively compare in a placebo controlled, blinded study, the effect of the combination of an anti-ictal medication and a laboratory proven antiepileptic drug for prevention of the development of epilepsy in an at risk population such as head trauma or stroke.

  1. The Effect of High and Low Antiepileptic Drug Dosage on Simulated Driving Performance in Person's with Seizures: A Pilot Study

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    Alexander M. Crizzle

    2015-10-01

    Full Text Available Background: Prior studies examining driving performance have not examined the effects of antiepileptic drugs (AED’s or their dosages in persons with epilepsy. AED’s are the primary form of treatment to control seizures, but they are shown to affect cognition, attention, and vision, all which may impair driving. The purpose of this study was to describe the characteristics of high and low AED dosages on simulated driving performance in persons with seizures. Method: Patients (N = 11; mean age 42.1 ± 6.3; 55% female; 100% Caucasian were recruited from the Epilepsy Monitoring Unit and had their driving assessed on a simulator. Results: No differences emerged in total or specific types of driving errors between high and low AED dosages. However, high AED drug dosage was significantly associated with errors of lane maintenance (r = .67, p < .05 and gap acceptance (r = .66, p < .05. The findings suggest that higher AED dosages may adversely affect driving performance, irrespective of having a diagnosis of epilepsy, conversion disorder, or other medical conditions. Conclusion: Future studies with larger samples are required to examine whether AED dosage or seizure focus alone can impair driving performance in persons with and without seizures.

  2. Quantitative EEG and Current Source Density Analysis of Combined Antiepileptic Drugs and Dopaminergic Agents in Genetic Epilepsy: Two Case Studies.

    Science.gov (United States)

    Emory, Hamlin; Wells, Christopher; Mizrahi, Neptune

    2015-07-01

    Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  3. SAFETY AND TOLERABILITY OF ANTIEPILEPTIC DRUGS AT WOMEN WITH EPILEPSY (DATA OF SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

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    K. Yu. Мukhin

    2015-01-01

    Full Text Available Women with epilepsy are referred to the special risk group due to the development of side effects of antiepileptic drugs (АED. Women’s neuroendocrinal disorders can be caused by the disease itself-epilepsy, as well as by the undertaken therapy. We have carried out a retrospective research in order to assess the safety and the tolerance of different AED at young girls and women of reproductive age. Was analyzed the data base of patients of Svt. Luka’s Institute of Child Neurology and Epilepsy, comprising all patients, who have been monitored in the period between 2000 and 2014 inclusive at the age between 15–40 years (n = 301. The research included patients, with different diagnosed forms of focal or generalized epilepsy, who were taking AED both during mono and polytherapy. Were analyzed all cases of neuroendocrinal, especially reproductive disorders, including the considerable gain of weight, menstrual disorder, sterility at AED background. Also was analyzed the result of all registered pregnancies at women with epilepsy (at the background of the antiepileptic therapy, as well as without treatment during pregnancy. The retrospective data analysis has revealed 51 сase (17 % in the group under review of expressed neuroendocrinal, reproductive and cosmetic side effects (including the menstrual disorder: dysmenorrhea, opsomenorrhea, amenorrhea, anovulatory cycles, sterility, unfavorable pregnancy outcomes, as well as cosmetic endocrinal side effects: obesity, hirsutism, hair loss. Most patients have got such combined side effects. Our research results show, that in most cases the pregnancy at women with epilepsy ends by birth of a healthy child, the pregnancy outcome depends on many factors, it also differs according to applied AED. Valproic acid drugs show the highest teratogenic risk. Also at the back ground of the therapy with valproic acid have been registered most cases of neuroendocrinal reproductive diseases at women

  4. Adult epileptic patients’ perception of social support during rational antiepileptic therapy

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    P. N. Vlasov

    2012-01-01

    Full Text Available The problem of stigmatization of a patient with epilepsy is frequently essential in restricting the capacities of his social performance. Society is often unready to recognize an epileptic patient as its equal member. The authors consider the main sources of social support (SS to patients with epilepsy: the patient’s family takes first place; friends and other important persons also play a major role. The perception of SS has been found to be related to the number of used antiepileptic drugs and the hemispheric lateralization of a leading epileptic focus.

  5. Opioids, antiepileptic and anticholinergic drugs and the risk of fractures in patients 65 years of age and older: a prospective population-based study.

    Science.gov (United States)

    Nurminen, Janne; Puustinen, Juha; Piirtola, Maarit; Vahlberg, Tero; Lyles, Alan; Kivelä, Sirkka-Liisa

    2013-05-01

    in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

  6. Comparative effectiveness of generic versus brand-name antiepileptic medications.

    Science.gov (United States)

    Gagne, Joshua J; Kesselheim, Aaron S; Choudhry, Niteesh K; Polinski, Jennifer M; Hutchins, David; Matlin, Olga S; Brennan, Troyen A; Avorn, Jerry; Shrank, William H

    2015-11-01

    The objective of this study was to compare treatment persistence and rates of seizure-related events in patients who initiate antiepileptic drug (AED) therapy with a generic versus a brand-name product. We used linked electronic medical and pharmacy claims data to identify Medicare beneficiaries who initiated one of five AEDs (clonazepam, gabapentin, oxcarbazepine, phenytoin, zonisamide). We matched initiators of generic versus brand-name versions of these drugs using a propensity score that accounted for demographic, clinical, and health service utilization variables. We used a Cox proportional hazards model to compare rates of seizure-related emergency room (ER) visit or hospitalization (primary outcome) and ER visit for bone fracture or head injury (secondary outcome) between the matched generic and brand-name initiators. We also compared treatment persistence, measured as time to first 14-day treatment gap, between generic and brand-name initiators. We identified 19,760 AED initiators who met study eligibility criteria; 18,306 (93%) initiated a generic AED. In the matched cohort, we observed 47 seizure-related hospitalizations and ER visits among brand-name initiators and 31 events among generic initiators, corresponding to a hazard ratio of 0.53 (95% confidence interval, 0.30 to 0.96). Similar results were observed for the secondary clinical endpoint and across sensitivity analyses. Mean time to first treatment gap was 124.2 days (standard deviation [sd], 125.8) for brand-name initiators and 137.9 (sd, 148.6) for generic initiators. Patients who initiated generic AEDs had fewer adverse seizure-related clinical outcomes and longer continuous treatment periods before experiencing a gap than those who initiated brand-name versions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: vigabatrin.

    Science.gov (United States)

    Edwin, Bismi; Joe, I Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the C-C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Aspectos farmacológicos relevantes de los antiepilépticos nuevos Relevant pharmacological aspects of the new antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Alicia Zapata Martínez

    2005-12-01

    Full Text Available Dada la importancia de la epilepsia como enfermedad crónica no transmisible, se decidió realizar una revisión de los fármacos nuevos que en los últimos años han sido comercializados para su tratamiento en el mundo. Se enfatizó en la necesidad de establecer una correcta relación beneficio/riesgo/costo a partir del conocimiento de la eficacia, seguridad, conveniencia y costo de los fármacos empleados en el tratamiento de cualquier enfermedad, y por supuesto, de la epilepsia. Los nuevos medicamentos antiepilépticos todavía no han demostrado de forma convincente ser superiores a los ya conocidos, y de los cuales también se exponen sus principales características farmacológicas. Aunque en la mayoría de las ocasiones no son mejores, sí no hay dudas que son más caros e incrementan el precio de los tratamientos.Due to the importance of epilepsy as a non-communicable chronic disease, it was decided to make a review of the new drugs that in the last years have been commercialized for its treatement in the world. Emphasis was given to the need of establishing a correct benefit/risk/cost relation, starting from the knowledge of efficiency, safety, convenience and cost of the drugs used in the treatment of any disease and, of course, of epilepsy. The new antiepileptic drugs have not proved yet to be superior than the already known, whose main pharmacological characteristics are also exposed. Though in most of the ocassions they are not better, they are undoubtedly more expensive and increase the prices of the treatments.

  9. Mortality rates and causes of death in children with epilepsy prescribed antiepileptic drugs: a retrospective cohort study using the UK General Practice Research Database.

    Science.gov (United States)

    Ackers, Ruth; Besag, Frank M C; Hughes, Elaine; Squier, Waney; Murray, Macey L; Wong, Ian C K

    2011-05-01

    Patients with epilepsy, including children, have an increased risk of mortality compared with the general population. Antiepileptic drugs (AEDs) were the most frequent class of drugs reported in a study looking at fatal suspected adverse drug reactions in children in the UK. The objective of the study was to identify cases and causes of death in a paediatric patient cohort prescribed AEDs with an associated epilepsy diagnosis. This was a retrospective cohort study supplemented with general practitioner-completed questionnaires, post-mortem reports and death certificates. The setting was UK primary care practices contributing to the General Practice Research Database. Participants were children and adolescents aged 0-18 years prescribed AEDs between 1993 and 2005. Causality assessment was undertaken by a consensus panel comprising paediatric specialists in neuropathology, neurology, neuropsychiatry, paediatric epilepsy, pharmacoepidemiology and pharmacy to determine crude mortality rate (CMR) and standardized mortality ratios (SMRs), and the likelihood of an association between AED(s) and the event of death. There were 6190 subjects in the cohort (contributing 26,890 person-years of data), of whom 151 died. Median age at death was 8.0 years. CMR was 56.2 per 10,000 person-years and the SMR was 22.4 (95% CI 18.9, 26.2). The majority of deceased subjects had severe underlying disorders. Death was attributable to epilepsy in 18 subjects; in 9 the cause of death was sudden unexpected death in epilepsy (SUDEP) [3.3 per 10 000 person-years (95% CI 1.5, 6.4)]. AEDs were probably (n = 2) or possibly (n = 3) associated causally with death in five subjects. Two status epilepticus deaths were associated causally with AED withdrawal. Children prescribed AEDs have an increased risk of mortality relative to the general population. Most of the deaths were in children with serious underlying disorders. A small number of SUDEP cases were identified. AEDs are not a major

  10. Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs.

    Science.gov (United States)

    Boothe, Dawn Merton; Dewey, Curtis; Carpenter, David Mark

    2012-05-01

    To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. Double-blinded, randomized, parallel, clinical trial. 46 AED-naïve dogs with naturally occurring epilepsy. Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs. Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 μg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], p.o., q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], p.o., q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end. Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.

  11. 75 FR 15440 - Guidance for Industry on Standards for Securing the Drug Supply Chain-Standardized Numerical...

    Science.gov (United States)

    2010-03-29

    ...] Guidance for Industry on Standards for Securing the Drug Supply Chain--Standardized Numerical... industry entitled ``Standards for Securing the Drug Supply Chain-Standardized Numerical Identification for... the Drug Supply Chain-Standardized Numerical Identification for Prescription Drug Packages.'' In the...

  12. Suicide-related behaviors in older patients with new anti-epileptic drug use: data from the VA hospital system

    Directory of Open Access Journals (Sweden)

    Dersh Jeffrey J

    2010-01-01

    Full Text Available Abstract Background The U.S. Food and Drug Administration (FDA recently linked antiepileptic drug (AED exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA, controlling for potential confounders. Methods VA and Medicare databases were used to identify veterans 66 years and older, who received a care from the VA between 1999 and 2004, and b an incident AED (monotherapy prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases, epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status. Results The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768 based on conditional logistic regression analysis was affective disorder (depression, anxiety, or post-traumatic stress disorder (PTSD; Odds Ratio 4.42, 95% CI 2.30 to 8.49 diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin. Conclusion Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.

  13. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine

  14. Brand name to generic substitution of antiepileptic drugs does not lead to seizure-related hospitalization: a population-based case-crossover study.

    Science.gov (United States)

    Polard, Elisabeth; Nowak, Emmanuel; Happe, André; Biraben, Arnaud; Oger, Emmanuel

    2015-11-01

    There is still controversy on brand-to-generic (B-G) antiepileptic drugs (AEDs) substitution. To assess association between B-G AED substitution and seizure-related hospitalization, we designed a case crossover using the French National Health Insurance Database. We identified a cohort of adult patients who filled a prescription in 2009-2011 for AEDs with at least one brand name and one generic form. The outcome date was defined as the date of hospitalization, coded G40.x or G41.x, with a G40/G41 hospitalization-free period of at least 1 year. Patients with a medical history of cancer and women who gave birth in 2009-2011 were excluded. We required individuals to have regular dispensations of AEDs within the year preceding the outcome date. Free patients were defined as patients who had only brand name dispensations before the control period. Eight thousand three hundred seventy nine patients (mean age ± standard deviation, 52.7 ± 18.8 years; sex ratio male/female, 1.27) were analyzed. Discordant pairs were 491 with B-G substitution in the control period only and 478 with B-G substitution in the case period only; odds ratio (95% confidence interval) 0.97 (0.86-1.10). No statistically significant interaction was detected among the four prespecified subgroup analyses (gender, age strata, free or non-free, and strict AED monotherapy or not). Controlling for non-seizure-related hospitalizations made no material difference. Sensitivity analyses yielded similar results. Brand-to-generic AED substitution was not associated with an elevated risk of seizure-related hospitalization. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Modification of polydopamine-coated Fe3O4 nanoparticles with multi-walled carbon nanotubes for magnetic-μ-dispersive solid-phase extraction of antiepileptic drugs in biological matrices.

    Science.gov (United States)

    Zhang, Ruiqi; Wang, Siming; Yang, Ye; Deng, Yulan; Li, Di; Su, Ping; Yang, Yi

    2018-06-01

    In this study, multi-walled carbon nanotubes were coated on the surface of magnetic nanoparticles modified by polydopamine. The synthesized composite was characterized and applied to magnetic-μ-dispersive solid-phase extraction of oxcarbazepine (OXC), phenytoin (PHT), and carbamazepine (CBZ) from human plasma, urine, and cerebrospinal fluid samples prior to analysis by a high-performance liquid chromatography-photodiode array detector. The extraction parameters were investigated and the optimum condition was obtained when the variables were set to the following: sorbent type, Fe 3 O 4 @polyDA-MWCNTs (length Graphical abstract Magnetic multi-walled carbon nanotube core-shell composites were applied as magnetic-μ-dispersive solid-phase extraction adsorbents for determination of antiepileptic drugs in biological matrices.

  16. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  17. [Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)].

    Science.gov (United States)

    Vespignani, H; de Zélicourt, M; Laurendeau, C; Fagnani, F; Levy-Bachelot, L; Murat, C; Kahane, P; de Toffol, B

    2014-02-01

    To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Antiepileptic Drug Titration and Related Health Care Resource Use and Costs.

    Science.gov (United States)

    Fishman, Jesse; Kalilani, Linda; Song, Yan; Swallow, Elyse; Wild, Imane

    2018-02-27

    Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs. To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance. Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review. Patients with epilepsy who were aged ≥ 18 years and had initiated an AED between January 1, 2014, and January 1, 2016, were followed for 6 months from AED initiation. Titration duration was the time from AED initiation to the beginning of treatment maintenance as determined by the physician. Outcomes were epilepsy-specific HRU (hospitalizations, emergency department visits, outpatient visits, physician referral, laboratory testing/diagnostic imaging, and phone calls) and related costs that occurred during the titration or maintenance treatment periods. Of 811 patients, 156, 128, 125, 120, 114, 107, and 61 initiated the following AEDs: levetiracetam, lamotrigine, lacosamide, valproate, topiramate, carbamazepine, and phenytoin, respectively. Most patients (619/803 [77.1%] with complete AED data) received monotherapy. Baseline characteristics were similar across AEDs (mean [SD] age, 36.6 [14.4] years; 59.0% male). Kaplan-Meier estimates of titration duration ranged from 3.3 weeks (phenytoin) to 8.1 weeks (lamotrigine). From titration to maintenance, the overall incidence of HRU per person-month decreased 54.5%-89.3% for each HRU measure except outpatient visits (24.6% decrease). Total epilepsy-related costs decreased from $80.48 to $42.77 per person-month, or 46.9% from titration to maintenance. AED titration periods had higher HRU rates and costs than AED maintenance, suggesting that use of AEDs with shorter titration requirements

  19. Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy.

    Science.gov (United States)

    Chen, B; Detyniecki, K; Choi, H; Hirsch, L; Katz, A; Legge, A; Wong, R; Jiang, A; Buchsbaum, R; Farooque, P

    2017-05-01

    The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. 922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  20. Patient emotions and perceptions of antiepileptic drug changes and titration during treatment for epilepsy.

    Science.gov (United States)

    Fishman, Jesse; Cohen, Greg; Josephson, Colin; Collier, Ann Marie; Bharatham, Srikanth; Zhang, Ying; Wild, Imane

    2017-04-01

    To investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy. Members of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme. All 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26-45years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥2 AEDs and 301 (87.2%) had ≥1 seizure in the previous 18months. All participants reported a medication change within the previous 12months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the

  1. Fighting Fire with Fire: Surgical Options for Patients with Drug-Resistant Epilepsy.

    Science.gov (United States)

    Bayer, Alina D; Blum, Andrew S; Asaad, Wael F; Roth, Julie; Toms, Steven A; Deck, Gina M

    2018-03-01

    While antiepileptic drugs (AEDs) provide adequate seizure control for most patients with epilepsy, ~30% continue to have seizures despite treatment with two or more AEDs.1 In addition to direct harm from seizures, poor epilepsy control correlates with higher mortality, morbidity, 2, 3 and cost to the healthcare system.4 In the subset of patients with persistent seizures despite medical management, surgical intervention and neuromodulation may be more effective. Primary care physicians and general neurologists should be aware of non-AED treatment options that are standard of care for drug- resistant epilepsy (DRE). [Full article available at http://rimed.org/rimedicaljournal-2018-03.asp].

  2. Drug: D05817 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05817 Drug Seletracetam (USAN/INN) ... C10H14F2N2O2 D05817.gif ... Neuropsychiatric agent ... DG02038 ... Piracetam... antiepileptics Chemical group: DG02506 ... Piracetam derivative Treatment of epilepsy

  3. Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?

    Science.gov (United States)

    Kanner, Andres M; Barry, John J; Gilliam, Frank; Hermann, Bruce; Meador, Kimford J

    2012-06-01

    To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)-related adverse events (AEs) in persons with epilepsy (PWE). The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory-II (BDI-II) scores >12 or the Centers of Epidemiologic Studies-Depression (CES-D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED-related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. Depressive and anxiety disorders worsen AED-related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  4. Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated Blood In Vitro

    Directory of Open Access Journals (Sweden)

    Hubertus Himmerich

    2014-01-01

    Full Text Available Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL-6 and tumor necrosis factor (TNF-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM, carbamazepine (CBZ, levetiracetam (LEV, lamotrigine (LTG, VPA, oxcarbazepine (OXC, topiramate (TPM, phenobarbital (PB, and lithium on the production of the following cytokines in vitro: interleukin (IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA’s anti-inflammatory properties.

  5. 49 CFR 219.701 - Standards for drug and alcohol testing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Standards for drug and alcohol testing. 219.701... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Drug and Alcohol Testing Procedures § 219.701 Standards for drug and alcohol testing. (a) Drug testing required or authorized by subparts B...

  6. Comparative persistence of antiepileptic drugs in patients with epilepsy: A STROBE-compliant retrospective cohort study

    Science.gov (United States)

    Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Su, Chien-Chou; Yang, Yea-Huei Kao; Huang, Chin-Wei; Lin, Swu-Jane; Setoguchi, Soko

    2016-01-01

    Abstract We compared persistence of antiepileptic drugs (AEDs) including carbamazepine, oxcarbazepine, gabapentin, lamotrigine, topiramate, valproic acid, and phenytoin in an Asian population with epilepsy. A retrospective cohort study was conducted by analyzing Taiwan's National Health Insurance Research Database (NHIRD). Adult epilepsy patients newly prescribed with AEDs between 2005 and 2009 were included. The primary outcome was persistence, defined as the treatment duration from the date of AED initiation to the date of AED discontinuation, switching, hospitalization due to seizure or disenrollment from databases, whichever came first. Cox proportional hazard models were used to estimate the risk of non-persistence with AEDs. Among the 13,061 new users of AED monotherapy (mean age: 58 years; 60% men), the persistence ranged from 218.8 (gabapentin) to 275.9 (oxcarbazepine) days in the first treatment year. The risks of non-persistence in patients receiving oxcarbazepine (adjusted hazard ratio [HR], 0.78; 95% CI, 0.74–0.83), valproic acid (0.88; 0.85–0.92), lamotrigine (0.72; 0.65–0.81), and topiramate (0.90; 0.82–0.98) were significantly lower than in the carbamazepine group. Compared with carbamazepine users, the non-persistence risk was higher in phenytoin users (1.10; 1.06–1.13), while gabapentin users (1.03; 0.98–1.09) had similar risk. For risk of hospitalization due to seizure and in comparison with carbamazepine users, oxcarbazepine (0.66; 0.58–0.74) and lamotrigine (0.46; 0.35–0.62) users had lower risk, while phenytoin (1.35; 1.26–1.44) users had higher risk. The results remained consistent throughout series of sensitivity and stratification analyses. The persistence varied among AEDs and was better for oxcarbazepine, valproic acid, lamotrigine, and topiramate, but worse for phenytoin when compared with carbamazepine. PMID:27583857

  7. The Effects of Fall-Risk-Increasing Drugs on Postural Control : A Literature Review

    NARCIS (Netherlands)

    de Groot, Maartje H.; van Campen, Jos P. C. M.; Moek, Marije A.; Tulner, Linda R.; Beijnen, Jos H.; Lamoth, Claudine J. C.

    Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of

  8. Antiepileptic drug prescribing before, during and after pregnancy: a study in seven European regions.

    Science.gov (United States)

    Charlton, Rachel; Garne, Ester; Wang, Hao; Klungsøyr, Kari; Jordan, Sue; Neville, Amanda; Pierini, Anna; Hansen, Anne; Engeland, Anders; Gini, Rosa; Thayer, Daniel; Bos, Jens; Puccini, Aurora; Nybo Andersen, Anne-Marie; Dolk, Helen; de Jong-van den Berg, Lolkje

    2015-11-01

    The aim of this study was to explore antiepileptic drug (AED) prescribing before, during and after pregnancy as recorded in seven population-based electronic healthcare databases. Databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the Clinical Practice Research Datalink, representing the rest of the UK, were accessed for the study. Women with a pregnancy starting and ending between 2004 and 2010, which ended in a delivery, were identified. AED prescriptions issued (UK) or dispensed (non-UK) at any time during pregnancy and the 6 months before and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy and was lowest during the third trimester, before returning to pre-pregnancy levels by 6 months following delivery. For all deliveries, the prevalence of AED prescribing during pregnancy was 51 per 10 000 pregnancies (CI95 49-52%) and was lowest in the Netherlands (43/10 000; CI95 33-54%) and highest in Wales (60/10 000; CI95 54-66%). In Denmark, Norway and the two UK databases lamotrigine was the most commonly prescribed AED; whereas in the Italian and Dutch databases, carbamazepine, valproate and phenobarbital were most frequently prescribed. Few women prescribed with AEDs in the 3 months before pregnancy were co-prescribed with high-dose folic acid: ranging from 1.0% (CI95 0.3-1.8%) in Emilia Romagna to 33.5% (CI95 28.7-38.4%) in Wales. The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care

  9. Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.

    Science.gov (United States)

    Spena, Giannantonio; Schucht, Philippe; Seidel, Kathleen; Rutten, Geert-Jan; Freyschlag, Christian Franz; D'Agata, Federico; Costi, Emanule; Zappa, Francesca; Fontanella, Marco; Fontaine, Denys; Almairac, Fabien; Cavallo, Michele; De Bonis, Pasquale; Conesa, Gerardo; Foroglou, Nicholas; Gil-Robles, Santiago; Mandonnet, Emanuel; Martino, Juan; Picht, Thomas; Viegas, Catarina; Wager, Michel; Pallud, Johan

    2017-04-01

    Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.

  10. Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

    Science.gov (United States)

    Vamecq, Joseph; Vallée, Louis; Lesage, Florian; Gressens, Pierre; Stables, James P

    2005-01-01

    The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

  11. The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

    Science.gov (United States)

    Rösche, J; Uhlmann, C; Weber, R; Fröscher, W

    2003-04-01

    Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

  12. Identification and preclinical testing of novel antiepileptic compounds.

    Science.gov (United States)

    Meldrum, B S

    1997-01-01

    Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high-frequency repetitive firing in cultured neurons and prolonging inactivation of voltage-dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of gamma-aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high-throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.

  13. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  14. Patients' perspectives on antiepileptic medication: relationships between beliefs about medicines and adherence among patients with epilepsy in UK primary care.

    OpenAIRE

    Chapman, S. C.; Horne, R.; Chater, A.; Hukins, D.; Smithson, W. H.

    2014-01-01

    BACKGROUND: Nonadherence to antiepileptic drugs (AEDs) can result in suboptimal outcomes for patients. AIM: This study aimed to assess the utility of a theory-based approach to understanding patient perspectives on AEDs and adherence. METHOD: Patients with epilepsy, identified by a GP case note review, were mailed validated questionnaires assessing their perceptions of AEDs and their adherence to them. RESULTS: Most (84.9%) of the 398 AED-treated respondents accepted the necessity of AEDs, bu...

  15. Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

    Science.gov (United States)

    Kostić, Nađa; Dotsikas, Yannis; Malenović, Anđelija; Medenica, Mirjana

    2013-11-15

    In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient Responses to Antiepileptic Drugs.

    Directory of Open Access Journals (Sweden)

    Yida Hu

    Full Text Available In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR patients, 11 well-healed (WH patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC group, while 10 patients were enrolled in the seizure-controlled (SC group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann's area 17 (BA17, compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN regions showed negative connectivity increased changes or

  17. Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy.

    Science.gov (United States)

    Guilfoyle, Shanna M; Follansbee-Junger, Katherine; Smith, Aimee W; Combs, Angela; Ollier, Shannon; Hater, Brooke; Modi, Avani C

    2018-01-01

    To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1 month following AED initiation. A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11 years) and adolescents (age = 12-18 years) were examined separately. A total of 380 youths with new onset epilepsy (M age  = 8.9 ± 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M = 25.08 ± 26.36) compared to adolescents (M = 12.36 ± 17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1 month after AED initiation in both age groups. Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  18. The antiepileptic Materia Medica of Pediacus Dioscorides.

    Science.gov (United States)

    Eadie, M J

    2004-09-01

    Since it was written about the middle of the 1st Century AD, and up to comparatively recent times, the great Herbal, or Materia Medica, of Dioscorides provided medicine with its chief source of information about what were then considered therapeutic substances. The work contained data on various materials of botanical, biological and mineral origin which were claimed to provide benefit to sufferers from epilepsy, though often with no clear underlying rationale for their use. Some of these materials continued to be used as antiepileptic remedies over many centuries till they were finally recognised to be without useful effect in the disorder. The longest survivor amongst the Dioscoridean antiepileptic remedies was a rather esoteric one, viz. two stones taken from the belly of a young swallow during the rising phase of the moon and also whilst the swallow's parent birds were absent from the nest. The stones, or one of them, were worn against the skin of the seizure sufferer. The use of the swallow stones for epilepsy was recommended as late as in the writings of Thomas Willis (1675).

  19. Possible drug-drug interaction between pregabalin and clozapine in patients with schizophrenia

    DEFF Research Database (Denmark)

    Schjerning, O; Lykkegaard, S; Damkier, P

    2015-01-01

    INTRODUCTION: Pregabalin is an antiepileptic drug with anti-anxiety properties and is approved for treatment of generalized anxiety disorder. Anxiety is common in patients with schizophrenia and pregabalin has been suggested as an off-label add-on treatment. METHODS: Pregabalin was added...... patient was less clear. DISCUSSION: This short report discusses the possible mechanism of a pregabalin-clozapine interaction....

  20. An RNAi-mediated screen identifies novel targets for next-generation antiepileptic drugs based on increased expression of the homeostatic regulator pumilio.

    Science.gov (United States)

    Lin, Wei-Hsiang; He, Miaomiao; Fan, Yuen Ngan; Baines, Richard A

    2018-05-02

    Despite availability of a diverse range of anti-epileptic drugs (AEDs), only about two-thirds of epilepsy patients respond well to drug treatment. Thus, novel targets are required to catalyse the design of next-generation AEDs. Manipulation of neuron firing-rate homoeostasis, through enhancing Pumilio (Pum) activity, has been shown to be potently anticonvulsant in Drosophila. In this study, we performed a genome-wide RNAi screen in S2R + cells, using a luciferase-based dPum activity reporter and identified 1166 genes involved in dPum regulation. Of these genes, we focused on 699 genes that, on knock-down, potentiate dPum activity/expression. Of this subgroup, 101 genes are activity-dependent based on comparison with genes previously identified as activity-dependent by RNA-sequencing. Functional cluster analysis shows these genes are enriched in pathways involved in DNA damage, regulation of cell cycle and proteasomal protein catabolism. To test for anticonvulsant activity, we utilised an RNA-interference approach in vivo. RNAi-mediated knockdown showed that 57/101 genes (61%) are sufficient to significantly reduce seizure duration in the characterized seizure mutant, para bss . We further show that chemical inhibitors of protein products of some of the genes targeted are similarly anticonvulsant. Finally, to establish whether the anticonvulsant activity of identified compounds results from increased dpum transcription, we performed a luciferase-based assay to monitor dpum promoter activity. Third instar larvae exposed to sodium fluoride, gemcitabine, metformin, bestatin, WP1066 or valproic acid all showed increased dpum promoter activity. Thus, this study validates Pum as a favourable target for AED design and, moreover, identifies a number of lead compounds capable of increasing the expression of this homeostatic regulator.

  1. Quality of antiepileptic drugs in sub-Saharan Africa: A study in Gabon, Kenya, and Madagascar.

    Science.gov (United States)

    Jost, Jeremy; Ratsimbazafy, Voa; Nguyen, Thu Trang; Nguyen, Thuy Linh; Dufat, Hanh; Dugay, Annabelle; Ba, Alassane; Sivadier, Guilhem; Mafilaza, Yattussia; Jousse, Cyril; Traïkia, Mounir; Leremboure, Martin; Auditeau, Emilie; Raharivelo, Adeline; Ngoungou, Edgard; Kariuki, Symon M; Newton, Charles R; Preux, Pierre-Marie

    2018-06-12

    Epilepsy is a major public health issue in low- and middle-income countries, where the availability and accessibility of quality treatment remain important issues, the severity of which may be aggravated by poor quality antiepileptic drugs (AEDs). The primary objective of this study was to measure the quality of AEDs in rural and urban areas in 3 African countries. This cross-sectional study was carried out in Gabon, Kenya, and Madagascar. Both official and unofficial supply chains in urban and rural areas were investigated. Samples of oral AEDs were collected in areas where a patient could buy or obtain them. Pharmacological analytical procedures and Medicine Quality Assessment Reporting Guidelines were used to assess quality. In total, 102 batches, representing 3782 units of AEDs, were sampled. Overall, 32.3% of the tablets were of poor quality, but no significant difference was observed across sites: 26.5% in Gabon, 37.0% in Kenya, and 34.1% in Madagascar (P = .7). The highest proportions of substandard medications were found in the carbamazepine (38.7%; 95% confidence interval [CI] 21.8-57.8) and phenytoin (83.3%; 95% CI 35.8-99.5) batches, which were mainly flawed by their failure to dissolve. Sodium valproate was the AED with the poorest quality (32.1%; 95% CI 15.8-42.3). The phenobarbital (94.1%; 95% CI 80.3-99.2) and diazepam (100.0%) batches were of better quality. The prevalence of substandard quality medications increased in samples supplied by public facilities (odds ratio [OR] 9.9; 95% CI 1.2-84.1; P < .04) and manufacturers located in China (OR 119.8; 95% CI 8.7-1651.9; P < .001). The prevalence of AEDs of bad quality increased when they were stored improperly (OR 5.4; 95% CI 1.2-24.1; P < .03). No counterfeiting was observed. However, inadequate AED storage conditions are likely to lead to ineffective and possibly dangerous AEDs, even when good-quality AEDs are initially imported. Wiley Periodicals, Inc. © 2018 International League Against

  2. Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population.

    Science.gov (United States)

    Pilotto, Chiara; Liu, Jo-Fen; Walker, David A; Whitehouse, William P

    2018-03-21

    Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. data was available on 117/120 (98%) children seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months). Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control. Copyright © 2018. Published by Elsevier Ltd.

  3. [The costs of new drugs compared to current standard treatment].

    Science.gov (United States)

    Ujeyl, Mariam; Schlegel, Claudia; Gundert-Remy, Ursula

    2013-01-01

    Until AMNOG came into effect Germany had free pricing of new drugs. Our exemplary work investigates the costs of new drugs that were licensed in the two years prior to AMNOG, and compares them to the costs of standard treatment that has been used in pivotal trials. Also, the important components of pharmaceutical prices will be illustrated. We retrospectively analysed the European Public Assessment Reports of proprietary medicinal products that the European Medicinal Agency initially approved in 2009 and 2010 and that were tested against an active control in at least one pivotal trial. If the standard treatment was a generic, the average pharmacy retail price of new drugs was 7.4 times (median 7.1) higher than that of standard treatment. If the standard treatment was an originator drug the average price was 1.4 times (median 1.2) higher than that of the new drug. There was no clear correlation of an increase in costs for new drugs and their "grade of innovation" as rated according to the criteria of Fricke. Our study shows that prices of new drugs must be linked to the evidence of comparative benefit; since German drug pricing is complex, cost saving effects obtained thereby will depend on a range of other rules and decisions. Copyright © 2013. Published by Elsevier GmbH.

  4. Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

    Science.gov (United States)

    López-García, Miguel A; Feria-Romero, Iris A; Serrano, Héctor; Rayo-Mares, Darío; Fagiolino, Pietro; Vázquez, Marta; Escamilla-Núñez, Consuelo; Grijalva, Israel; Escalante-Santiago, David; Orozco-Suarez, Sandra

    2017-06-01

    Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  5. Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, lacosamide and oxcarbazepine.

    Science.gov (United States)

    Zaccara, Gaetano; Giovannelli, Fabio; Maratea, Dario; Fadda, Valeria; Verrotti, Alberto

    2013-09-01

    Analysis of overall tolerability and neurological adverse effects (AEs) of eslicarbazepine acetate (ESL), lacosamide (LCM) and oxcarbazepine (OXC) from double-blind, placebo-controlled trials. Indirect comparisons of patients withdrawing because of AEs, and the incidence of some vestibulocerebellar AEs between these three antiepileptic dugs (AEDs). We searched MEDLINE for all randomized, double-blind, placebo-controlled trials investigating therapeutic effects of fixed oral doses of ESL, LCM and OXC in patients with drug resistant epilepsy. Withdrawal rate due to AEs, percentages of patients with serious AEs, and the proportion of patients experiencing any neurological AE, nausea and vomiting were assessed for their association with the experimental drug. Analyses were performed between recommended daily doses of each AED according to the approved summary of product characteristics (SPC). Risk differences were used to evaluate the association of any AE [99% confidence intervals (CIs)] or study withdrawals because of AEs (95% CIs) with the experimental drug. Indirect comparisons between withdrawal rate and AEs dizziness, coordination abnormal/ataxia and diplopia were estimated according to network meta-analysis (Net-MA). Eight randomized, placebo-controlled, double-blind trials (4 with ESL, 3 with LCM, and 1 with OXC) were included in our analysis. At high doses (OXC 1200mg, ESL 1200mg and LCM 400mg) there was an increased risk of AE-related study withdrawals compared to placebo for all drugs. Several AEs were associated with the experimental drug. Both number and frequency of AEs were dose-related. At high recommended doses, patients treated with OXC withdrew from the experimental treatment significantly more frequently than patients treated with ESL and LCM. Furthermore, the AEs coordination abnormal/ataxia and diplopia were significantly more frequently observed in patients treated with OXC compared to patients treated with LCM and ESL. The overall tolerability

  6. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy.

    Science.gov (United States)

    Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Buchsbaum, Richard; Detyniecki, Kamil

    2017-11-01

    Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs. Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P<0.001, OR=6.87). Levetiracetam was also significantly (P<0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P<0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE

  7. The roles of variants in human multidrug resistance (MDR1 gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1 polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T, we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01. However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians, no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.

  8. Behavioral effects of antiepileptic drugs in rats: Are the effects on mood and behavior detectable in open-field test?

    Science.gov (United States)

    Zimcikova, Eva; Simko, Julius; Karesova, Iva; Kremlacek, Jan; Malakova, Jana

    2017-11-01

    Behavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. The open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. The experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

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    P Padma Rao

    2015-01-01

    Full Text Available Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with established parametric standards for manufacturing the drug. Materials and Methods: Pharmacognostic studies on leaves and young aerial parts of authentic samples of J. virginiana L. have been carried out; physico-chemical parameters of raw drug viz., extractive values, ash values, formulation, besides weight per mL, total solids, alcohol content along with High Performance Thin Layer Chromatography (HPTLC and ultraviolet visible studies have been worked out for mother tincture. Results: The leaves are needles, narrow and sharp at tips; stems are round with greyish white to brown bark possessing small lenticels and covered by imbricate leaves. Epidermal cells in the surface have polygonal linear sides with pitted walls containing crystals and starch. Stomata exclusively occur on the adaxial surface in linear rows. Hypodermis of leaf in T.S. is marked with 1-2 layered lignified sclerenchyma. 2-4 secretory canals are present with one conspicuously beneath midvein bundle. The young terminal axis is sheathed by two closely surrounding leaves while the mature stem possess four leaf bases attached. Vascular tissue of stem possesses predominant xylem surrounded by phloem containing sphaeraphides, prismatic crystals and starch grains. Uniseriate rays occur in the xylem. Mature stem possess shrivelled cork, followed by the cortex. Physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and

  10. Epilepsy, anti-epileptic medication use and risk of cancer

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Carstensen, Lisbeth; Wohlfahrt, Jan

    2014-01-01

    Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti-epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents ≥ 16 years ...

  11. Signaling to P-glycoprotein-A new therapeutic target to treat drug-resistant epilepsy?

    NARCIS (Netherlands)

    Hartz, A.M.; Notenboom, S.; Bauer, B.

    2009-01-01

    Epilepsy affects more than 60 million people worldwide. While most patients can be treated with antiepileptic drugs, up to 40% of patients respond poorly to pharmacotherapy. This drug resistance is not well understood and presents a major clinical problem. In this short review we provide background

  12. Effects of Various Antiepileptics Used to Alleviate Neuropathic Pain on Compound Action Potential in Frog Sciatic Nerves: Comparison with Those of Local Anesthetics

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    Yuhei Uemura

    2014-01-01

    Full Text Available Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+ and Ca2+ channels, glutamate-receptor inhibition, and GABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine concentration dependently reduced the peak amplitude of the CAP (IC50=0.44 and 0.50 mM, resp.. Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50=0.23 mM. These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.

  13. New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

    Science.gov (United States)

    2015-07-01

    may become a key piece in the arsenal of antiepileptic drugs in mesial temporal lobe epilepsy . Thereby, screening for a presynaptic action site may be...neuronal damage, mesial temporal lobe epilepsy (MTLE) in ~30% of patients, and resistance to available anticonvulsant drugs. Therefore, it is of... temporal lobe epilepsy (MTLE) (months 1-12). Working hypothesis: Drugs acting on presynaptic Ca 2+ channels, autoreceptors, and SV2a will be more

  14. Standardization Study of Antifertility Drug - Pippalyadiyoga

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    D. Shaila

    2005-01-01

    Full Text Available The present paper deals with the standardization study of pippalyadiyoga powder. It is used as a long acting contraceptive. The standardization of compound drug has been achieved by physico-chemical analysis and high performance liquid chromatography (HPLC fingerprint studies. Quantitative evaluation of borax in pippalyadiyoga showed 19.08% as sodium borate. RP-HPLC was performed using methanol and water as mobile phase. The detection and quantification was performed at a wavelength of 345 nm. Linearity of detector response for piperine was between the concentrations 0.005% to 0.1%. The correlation coefficient obtained for the linearity was 0.998. The recovery value of standard piperine was 99.4%. Low value of standard deviation and coefficient of variation are indicative of high precision of the method. Quantitative evaluation of piperine in pippalyadiyoga was found to be 0.339%.

  15. Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

    Science.gov (United States)

    Lwu, Shelly; Hamilton, Mark G; Forsyth, Peter A; Cairncross, J Gregory; Parney, Ian F

    2010-02-01

    An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

  16. Papel de los fármacos antiepilépticos genéricos en el tratamiento de la epilepsia infantil Role of generic antiepileptic drugs in the treatment of childhood epilepsy

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    Jaime Campos-Castelló

    2009-01-01

    Full Text Available La aparición de fármacos genéricos en el mercado, en sustitución de marcas registradas®, y las adecuadas regulaciones de las autoridades sanitarias en los distintos países ha condicionado hasta la actualidad una polémica sobre el riesgo costo/beneficio de tal sustitución en el paciente afecto de epilepsia. El binomio costo/beneficio debe dar por demostrado de manera clara que el paciente puede beneficiarse de tal sustitución sin correr riesgo alguno significativo. Por ello se valoran los distintos aportes en la literatura médica al respecto, que analizan estos riesgos y beneficios y en especial el hecho esencial de la bioequivalencia de ambas formulaciones, en especial en las situaciones de aquellos fármacos antiepilépticos de margen o índice terapéutico estrecho que hagan inviable la equivalencia de la biodisponibilidad del fármaco, la ausencia de repercusión clínica real en el paciente así como la evidencia que existe un beneficio económico claro al valorar el citado binomio riesgo/beneficio. La revisión efectuada señala la clara existencia de desventajas potenciales del cambio de un fármaco antiepiléptico (FAE original de marca a un genérico como: distinta biodisponibilidad, bioequivalencia no demostrada, riesgo de reaparición de crisis en pacientes controlados y variabilidad de la respuesta de los FAE en el paciente epiléptico, imposible de predecir. Por ello se aconseja valorar la importancia de un fracaso terapéutico tras un cambio a genérico, en especial en casos de margen terapéutico estrecho, la biodisponibilidad permisible con valoración de la variabilidad individual del paciente, situación médico-legal de tal cambio y la realidad de los ahorros y costos potenciales derivados.The use of generic instead of trade mark antiepileptic drugs raises the question of cost/benefit risks. The efficacy and side effects of the generic AED should be similar to the trade mark drugs. Otherwise, the substitution is not

  17. Drug taper during long-term video-EEG monitoring

    DEFF Research Database (Denmark)

    Guld, A. T.; Sabers, A.; Kjaer, T. W.

    2017-01-01

    Objectives: Anti-epileptic drugs (AED) are often tapered to reduce the time needed to record a sufficient number of seizure during long-term video-EEG monitoring (LTM). Fast AED reduction is considered less safe, but few studies have examined this. Our goal is to examine whether the rate of AED r...

  18. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Science.gov (United States)

    Zhu, Fei; Lang, Sen-Yang; Wang, Xiang-Qing; Shi, Xiao-Bing; Ma, Yun-Feng; Zhang, Xu; Chen, Ya-Nan; Zhang, Jia-Tang

    2015-01-01

    Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64–44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure

  19. Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

    Directory of Open Access Journals (Sweden)

    Fei Zhu

    2015-01-01

    Full Text Available Background: It is important to choose an appropriate antiepileptic drug (AED to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ and valproate (VPA, have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM, oxcarbazepine (OXC, lamotrigine (LTG, or levetiracetam (LEV, were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07. CBZ exhibited the highest 12-month remission rate (85.55%, which was significantly higher than those of TPM (69.38%, P = 0.006, LTG (70.79%, P = 0.001, LEV (72.54%, P = 0.005, and VPA (73.33%, P = 0.002. CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%, rashes (7.76%, abnormal hepatic function (6.24%, and drowsiness (6.24%. Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first

  20. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling

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    M Vijey Aanandhi

    2015-01-01

    Full Text Available Patients with temporal lobe epilepsy (TLE are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and various open source computational tools were used to perform the study. AutoDock 4.2 MGL tools, Pymol visualize tools, Patch dock server, and Swarm Dock servers (protein-protein docking were used to perform the molecular modeling. FTsite and computed atlas of surface topography of protein open source server were used to understand the pocket and ligand binding information respectively. Toxtree application was used to determine the toxicity profile of the drug by Cramers rule. The obtained molecular docking models (Caspase 3, Procaspase 8, and Fas-associated death domain [FADD] with selected compounds (Clonazepam, Clobazepam, and Retigabine showed promising trio blocking event of FADD, Caspase 3, and Procaspase 8 (−6.66 kcal, −8.1 kcal, 6.46 kcal by Clonazepam respectively. Protein-protein interaction study (Swarm Dock, Patch Dock server indicated promising results that helped to establish our hypothesis. Toxtree showed a quantitative structure toxicity relationship report that helps to clarify the toxicity of the selected compounds. Clonazepam showed a trio inhibition property that may lead to develop a new era of the new generation benzodiazepine prototype drugs in the future. Filtered compounds will further process for higher in vitro, in vivo models for better understanding of the mechanism.

  1. Anti-epileptic drug intake adherence: the value of the blood drug level measurement and the clinical approach Aderência à ingestão de medicamentos antiepilépticos: o valor da avaliação dos níveis sanguíneos e a abordagem clínica

    Directory of Open Access Journals (Sweden)

    MARLEIDE DA MOTA GOMES

    1998-12-01

    Full Text Available It was evaluated the patient antiepileptic drug (AED intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient and compared with the self-reported antiepileptic medication non-adherence, AED blood level according to the range (therapeutic or not, and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not. The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the self-reported adherence have to be also considered for this sort of evaluation.Avaliou-se a aderência à ingesta de drogas antiepilépticas (DAE em estudo piloto transversal conduzido em ambulatório de hospital neurológico universitário. Noventa e três amostras sanguíneas com concentraç��o de DAE (fenobarbital, fenitoína, carbamazepina foram analisadas de 24 pacientes. A variabilidade dos níveis sanguíneos das DAE (em estado estável - steady state period, analizada por meio do coeficiente de variação foi comparada com a auto-referida não aderência à ingesta da DAE, níveis sanguíneos das DAE de acordo com a faixa (terapêutica ou não e o controle das crises epilépticas. Não foi observada correlação forte entre o maior valor da variabilidade e os outros três parâmetros de aderência, apesar da maior correlação com o nível sanguíneo (terapêutico ou não. A avaliação do nível sérico isolado, exceto em caso de extrema baixa aderência e

  2. Direct Determination of a Small-Molecule Drug, Valproic Acid, by an Electrically-Detected Microcantilever Biosensor for Personalized Diagnostics

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    Long-Sun Huang

    2015-01-01

    Full Text Available Direct, small-molecule determination of the antiepileptic drug, valproic acid, was investigated by a label-free, nanomechanical biosensor. Valproic acid has long been used as an antiepileptic medication, which is administered through therapeutic drug monitoring and has a narrow therapeutic dosage range of 50–100 μg·mL−1 in blood or serum. Unlike labeled and clinically-used measurement techniques, the label-free, electrical detection microcantilever biosensor can be miniaturized and simplified for use in portable or hand-held point-of-care platforms or personal diagnostic tools. A micromachined microcantilever sensor was packaged into the micro-channel of a fluidic system. The measurement of the antiepileptic drug, valproic acid, in phosphate-buffered saline and serum used a single free-standing, piezoresistive microcantilever biosensor in a thermally-controlled system. The measured surface stresses showed a profile over a concentration range of 50–500 μg·mL−1, which covered the clinically therapeutic range of 50–100 μg·mL−1. The estimated limit of detection (LOD was calculated to be 45 μg·mL−1, and the binding affinity between the drug and the antibody was measured at around 90 ± 21 μg·mL−1. Lastly, the results of the proposed device showed a similar profile in valproic acid drug detection with those of the clinically-used fluorescence polarization immunoassay.

  3. Effect of impaired ambulation and anti-epileptic drug intake on vitamin D status of children with cerebral palsy.

    Science.gov (United States)

    Seth, Anju; Aneja, Satinder; Singh, Ritu; Majumdar, Ritu; Sharma, Neera; Gopinath, Muthuselvan

    2017-08-01

    Children with cerebral palsy (CP) are vulnerable to developing vitamin D deficiency. There is little information on the prevalence and severity of vitamin D deficiency in these patients. To study vitamin D status in children with CP with special reference to their intake of anti-epileptic drugs (AED) and ambulatory status. The relative effects of AED use and ambulatory status on the vitamin D status of 120 children with CP aged 2-10 years were examined in this observational study. The patients were classified into four groups (30 in each) on the basis of AED use and ambulatory status: ambulatory (CPA), ambulatory receiving AED (CPAD), non-ambulatory (CPNA) and non-ambulatory receiving AED (CPNAD). A control group of 30 age-matched healthy children was also included. Parameters assessed included dietary calcium intake, sun exposure, serum total and ionised calcium (tCa, iCa), inorganic phosphate (iP), alkaline phosphatase (ALP), parathormone (PTH), 25 hydroxy vitamin D [25(OH)D] levels and a wrist radiograph to detect rickets. Vitamin D status was defined on the basis of serum 25(OH)D levels as normal (>50 nmol/L), mild deficiency (25-50 nmol/L), moderate deficiency (12.5-25 nmol/L), severe deficiency (D levels in patients with CP were 35.6 (26.75-64) nmol/L compared with 60 (37-69.25) nmol/L in controls (p = 0.04). Sixty per cent of children with CP and 36.7% of controls were vitamin D-deficient [25(OH)D D-deficient with median (IQR) 25(OH)D levels of 33.5 (12.5-45.25) nmol/L. Also, 53.3% of them had raised ALP and 17.2% raised PTH levels. Children with CP are highly vulnerable to vitamin D deficiency. In these patients, AED use and lack of sun exposure contribute towards poor vitamin D status, the effect being more pronounced when they co-exist.

  4. Comparative effectiveness of eight antiepileptic drugs in adults with focal refractory epilepsy: the influence of age, gender, and the sequence in which drugs were introduced onto the market.

    Science.gov (United States)

    Mäkinen, Jussi; Peltola, Jukka; Raitanen, Jani; Alapirtti, Tiina; Rainesalo, Sirpa

    2017-07-01

    The first objective was to determine the long-term retention rate of eight antiepileptic drugs (AEDs) commonly used as adjunctive therapy in adults with focal refractory epilepsy. Second, we assessed the effects of age and gender on retention rates. Third, we examined if the retention rate could be influenced by the sequence in which the AEDs had entered the market. Patients with focal refractory epilepsy treated with any of the eight AEDs in Tampere University Hospital were identified retrospectively (N = 507). Retention rates were evaluated with the Kaplan-Meier method. Follow-up started at the first date of treatment and each individual was followed a maximum of 36 months. We calculated the following 3-year retention rates: lacosamide 77.1% (N = 137), lamotrigine 68.3% (N = 177), levetiracetam 66.7% (N = 319), clobazam 65.6% (N = 130), topiramate 61.6% (N = 178), zonisamide 60.4% (N = 103), pregabalin 54.6% (N = 127), and gabapentin 40.2% (N = 66). Lacosamide, levetiracetam, and clobazam were the most effective AEDs in the elderly. The retention rate for pregabalin was higher in males (65%) than females (51%) whereas females had higher retention rates for both topiramate (72 vs. 58%) and zonisamide (67 vs. 57%). The retention rate was influenced by the sequence in which these AEDs entered the market. We provide important information about practical aspects of these eight AEDs, revealing that there are differences in their effectiveness as adjunctive treatment for focal refractory epilepsy. Most importantly, the retention rate appears to be influenced by the sequence in which these AEDs were introduced onto the market.

  5. Budget impact analysis of adjunctive therapy with lacosamide for partial-onset epileptic seizures in Belgium.

    Science.gov (United States)

    Simoens, Steven

    2011-01-01

    This study aims to compute the budget impact of lacosamide, a new adjunctive therapy for partial-onset seizures in epilepsy patients from 16 years of age who are uncontrolled and having previously used at least three anti-epileptic drugs from a Belgian healthcare payer perspective. The budget impact analysis compared the 'world with lacosamide' to the 'world without lacosamide' and calculated how a change in the mix of anti-epileptic drugs used to treat uncontrolled epilepsy would impact drug spending from 2008 to 2013. Data on the number of patients and on the market shares of anti-epileptic drugs were taken from Belgian sources and from the literature. Unit costs of anti-epileptic drugs originated from Belgian sources. The budget impact was calculated from two scenarios about the market uptake of lacosamide. The Belgian target population is expected to increase from 5333 patients in 2008 to 5522 patients in 2013. Assuming that the market share of lacosamide increases linearly over time and is taken evenly from all other anti-epileptic drugs (AEDs), the budget impact of adopting adjunctive therapy with lacosamide increases from €5249 (0.1% of reference drug budget) in 2008 to €242,700 (4.7% of reference drug budget) in 2013. Assuming that 10% of patients use standard AED therapy plus lacosamide, the budget impact of adopting adjunctive therapy with lacosamide is around €800,000-900,000 per year (or 16.7% of the reference drug budget). Adjunctive therapy with lacosamide would raise drug spending for this patient population by as much as 16.7% per year. However, this budget impact analysis did not consider the fact that lacosamide reduces costs of seizure management and withdrawal. The literature suggests that, if savings in other healthcare costs are taken into account, adjunctive therapy with lacosamide may be cost saving.

  6. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study

    Science.gov (United States)

    Zhu, Pan; He, Ru-Qian; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

    2015-01-01

    Objective To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice. Methods Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure. Results This study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]). Conclusion LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not. PMID:26147937

  7. Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study.

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    Qing-Yi Zeng

    Full Text Available To evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs for monotherapy of adult patients with focal epilepsy in routine clinical practice.Adult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ, valproate (VPA, lamotrigine (LTG, topiramate (TPM, or oxcarbazepine (OXC as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD, were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.This study included 654 patients: CBZ (n=125, VPA (n=151, LTG (n=135, TPM (n=76, and OXC (n=167. The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]; TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74], and OXC was better than VPA (0.86 [0.78-0.96]. After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82] and OXC (LTG vs. OXC, 0.76 [0.63-0.93]; OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40].LTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.

  8. Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

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    Manna Jose

    2014-01-01

    Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

  9. Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center

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    Priscila de Freitas-Lima

    2013-11-01

    Full Text Available Objective To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. Method Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. Results Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% and 58.9% of the patients, respectively. Among the new agents, lamotrigine was the most commonly prescribed (36.6% of the patients. At least one old agent was identified in 103 out of the 104 polytherapies, while at least one new agent was prescribed to 70.5% of the population. The most prevalent combination was carbamazepine + clobazam + lamotrigine. The mean AED load found was 3.3 (range 0.4–7.7. Conclusion The pattern of use of individual drugs, although consistent with current treatment guidelines, is strongly influenced by the public health system.

  10. ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

    Science.gov (United States)

    Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

    2009-01-01

    Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

  11. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

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    Martins, H H; Alonso, N B; Vidal-Dourado, M; Carbonel, T D; de Araújo Filho, G M; Caboclo, L O; Yacubian, E M; Guilhoto, L M

    2011-11-01

    We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Your brain on drugs: imaging of drug-related changes in the central nervous system.

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    Tamrazi, Benita; Almast, Jeevak

    2012-01-01

    Drug abuse is a substantial problem in society today and is associated with significant morbidity and mortality. Various drugs are associated with serious complications affecting the brain, and it is critical to recognize the imaging findings of these complications to provide prompt medical management. The central nervous system (CNS) is a target organ for drugs of abuse as well as specific prescribed medications. Drugs of abuse affecting the CNS include cocaine, heroin, alcohol, amphetamines, toluene, and cannabis. Prescribed medications or medical therapies that can affect the CNS include immunosuppressants, antiepileptics, nitrous oxide, and total parenteral nutrition. The CNS complications of these drugs include neurovascular complications, encephalopathy, atrophy, infection, changes in the corpus callosum, and other miscellaneous changes. Imaging abnormalities indicative of these complications can be appreciated at both magnetic resonance (MR) imaging and computed tomography (CT). It is critical for radiologists to recognize complications related to drugs of abuse as well as iatrogenic effects of various medications. Therefore, diagnostic imaging modalities such as MR imaging and CT can play a pivotal role in the recognition and timely management of drug-related complications in the CNS.

  13. Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

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    Subramanian Palani

    2016-01-01

    Full Text Available Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of authentic raw drug have been carried out; physicochemical parameters, namely, extractive value, ash values, formulation besides weight per mL, total solids, alcohol content along with high-performance thin layer chromatography (HPTLC and ultraviolet studies for mother tincture have been worked out. Results: Roots are blackish-brown, wiry, rounded with irregular striations, tortuous; internally, it is softwood, light-yellow, and fracture fibrous. Phellem is 8-10 layered, discontinuous, and tanniniferous. Phellogen is two-layered and contains inulin crystals in few. Outer phelloderm is 12-16 layered often containing spherocrystals and associated with stone cells. Secondary phloem is up to 25 layered. Xylem is in the form of strips. The physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and organoleptic characters along with anatomical and physicochemical studies are diagnostic to establish standards for the drug.

  14. Etiologic features and utilization of antiepileptic drugs in people with chronic epilepsy in China: Report from the Epilepsy Cohort of Huashan Hospital (ECoH).

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    Ge, Yan; Yu, Peimin; Ding, Ding; Wang, Ping; Shi, Yunbo; Zhao, Ting; Tang, Xinghua; Hong, Zhen

    2015-10-01

    Chronic epilepsy is estimated to affect more than 2 million people in China. However, data of its clinical characteristics was rarely reported in China. In the present study, we summarized the etiologic features and utilization patterns of antiepileptic drugs (AEDs) in people with chronic epilepsy in a tertiary medical center in China. We prospectively recruited people with chronic epilepsy treated at the Epilepsy Outpatient Clinic of Huashan Hospital during October 2009 to August 2013. Demographic data, clinical characteristics, AED treatment, epilepsy-associated risk factors and medical history, and results of supplementary examinations of each participant were collected retrospectively via an interviewer-administered questionnaire and confirmed by the medical records. Among 554 people with chronic epilepsy, 58.0% of them were male, 66.8% had focal seizure, and 29.2% had symptomatic cause. Developmental anomalies of cerebral structure (16.7%) and cerebral trauma (16.7%) shared the leading cause of symptomatic epilepsy among children with epilepsy. While cerebral trauma (29.1%) and cerebrovascular disorder (36.4%) were the most common causes in groups of adults and elderly. Fifty percent of participants were taking AED monotherapy. Proportions of people with idiopathic, cryptogenic and symptomatic epilepsy treated by multitherapy were 35%, 46% and 45.6%, respectively. Valproic acid (VPA) was the most frequently utilized AED as monotherapy (32.7%) and within multitherapy (62.5%). This hospital-based study reported that etiologic features were diverse in different age groups of people with chronic epilepsy. VPA was widely utilized to treat chronic epilepsy in mainland China. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy.

    Science.gov (United States)

    Herkes, G K; Eadie, M J

    1990-07-01

    Salivary levels of phenytoin, phenobarbitone, carbamazepine and carbamazepine-epoxide correlate with the simultaneous plasma water levels of these substances, after correcting for the effects of pH differences between saliva and plasma in the case of phenobarbitone. Saliva is easy and painless to collect, and salivary levels of the drugs are conveniently measured. Frequent (often daily) monitoring of pre-dose morning anticonvulsant drug concentrations in saliva over periods of weeks or months in 3 groups of epileptic subjects showed that (i) in some but not all poorly controlled epileptic patients seizures tended to occur on days when salivary anticonvulsant levels were lower than on non-seizure days, (ii) in such subjects it was possible to estimate an anticipated optimal drug concentration and dose to minimize seizure activity from the plot of seizure frequency against drug concentrations, (iii) in women with 'catamenial' epilepsy, salivary anticonvulsant levels were lower on perimenstrual days than at mid-cycle in half of the subjects studied, and (iv) in pregnant epileptic women the time course of the change in drug levels relative to dose could be followed more closely throughout pregnancy and the post-natal period than was practicable when using blood level measurements. Frequent measurement of salivary anticonvulsant concentrations appears a promising and inexpensive adjunct to the investigation and management of certain problem areas in epilepsy.

  16. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    DEFF Research Database (Denmark)

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  17. Interaction of an antiepileptic drug, lamotrigine with human serum albumin (HSA): Application of spectroscopic techniques and molecular modeling methods.

    Science.gov (United States)

    Poureshghi, Fatemeh; Ghandforoushan, Parisa; Safarnejad, Azam; Soltani, Somaieh

    2017-01-01

    Lamotrigine (an epileptic drug) interaction with human serum albumin (HSA) was investigated by fluorescence, UV-Vis, FTIR, CD spectroscopic techniques, and molecular modeling methods. Binding constant (K b ) of 5.74×10 3 and number of binding site of 0.97 showed that there is a slight interaction between lamotrigine and HSA. Thermodynamic studies was constructed using the flourimetric titrations in three different temperatures and the resulted data used to calculate the parameters using Vant Hoff equation. Decreased Stern Volmer quenching constant by enhanced temperature revealed the static quenching mechanism. Negative standard enthalpy (ΔH) and standard entropy (ΔS) changes indicated that van der Waals interactions and hydrogen bonds were dominant forces which facilitate the binding of Lamotrigine to HSA, the results were confirmed by molecular docking studies which showed no hydrogen binding. The FRET studies showed that there is a possibility of energy transfer between Trp214 and lamotrigine. Also the binding of lamotrigine to HSA in the studied concentrations was not as much as many other drugs, but the secondary structure of the HSA was significantly changed following the interaction in a way that α-helix percentage was reduced from 67% to 57% after the addition of lamotrigine in the molar ratio of 4:1 to HSA. According to the docking studies, lamotrigine binds to IB site preferably. Copyright © 2016. Published by Elsevier B.V.

  18. Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

    Science.gov (United States)

    Wolfart, Jakob; Laker, Debora

    2015-01-01

    Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

  19. [Prevalence of psychoactive drug consumption in an obese population].

    Science.gov (United States)

    Cerdá Esteve, Maria A; Barral Tafalla, Diego; Gudelis, Mindaugas; Goday, Albert; Farre Albaladejo, Magi; Cano, Juan F

    2010-04-01

    To establish the prevalence of psychoactive drug consumption in an obese population. We collected data from the clinical records of obese patients attending the Endocrinology and Nutrition Department and Psychiatry Department of Hospital del Mar between June 2005 and May 2006 (n=259). We recorded anthropometric, epidemiological and toxicological data. We also investigated the prevalence of concomitant diseases in this population. Psychoactive drugs were consumed by 37% of obese patients, mainly antidepressants (27%), anxiolytics, sedatives and hypnotics, and anticonvulsants. Moreover, 15% of all patients received combination treatment with two or more psychoactive drugs, mostly the association of an antidepressant and an antiepileptic drug. The prevalence of psychoactive drug consumption in our sample was higher than prevalence data observed in the general population, with antidepressant consumption being three-fold higher. Copyright 2009 SEEN. Published by Elsevier Espana. All rights reserved.

  20. Prenatal exposure to antiepileptic drugs and dental agenesis.

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    Pernille E Jacobsen

    Full Text Available OBJECTIVE: The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used. METHODS: Data on 214 exposed and 255 unexposed children, aged 12-18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis. RESULTS: Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8-3.6]. The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3-7.4] in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4-51.9] in children exposed to valproate and carbamazepine or oxcarbazepine in combination. CONCLUSIONS: The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate.

  1. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part II: Pharmacological issues and further understanding.

    Science.gov (United States)

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions. The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic enzymes such as CYPs and UGTs, and transporters such as P-gp, implies that the amount of these proteins increases when they are induced; this is almost always explained by increasing synthesis mediated by the so-called nuclear receptors (constitutive androstane, estrogen, glucocorticoid receptors and pregnaneX receptors). Although parti provides correction factors for AEDs, extrapolation from an average to an individual patient may be influenced by administration route, absence of metabolic enzyme for genetic reasons, and presence of inhibitors or other inducers. AED pharmacodynamic DDIs may also be important. Six patients with extreme sensitivity to AED inductive effects are described. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  2. Drug hypersensitivity syndrome

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    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  3. Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

    Science.gov (United States)

    Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

    2017-06-23

    The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Evolução sócio-profissional de 140 pacientes epilépticos submetidos a tratamento medicamentoso The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy

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    Luís Marques-Assis

    1968-09-01

    Full Text Available É estudada a evolução sócio-profissional de 140 doentes epilépticos, submetidos apenas a tratamento medicamentoso. Foram empregadas drogas de fácil aquisição em nosso meio (barbitúricos, hidantoinatos, primidona e trimetadiona, utilizadas isolada ou combinadamente. No estudo foram consideradas basicamente as atividades escolares, domésticas e profissionais. A evolução sócio-profissional foi estudada em relação às manifestações clínicas, ao tempo de doença, à freqüência das crises e ao padrão eletrencefalográfico. Os resultados, expressos em índices percentuais, permitiram ao autor concluir que na maioria dos pacientes epilépticos, convenientemente tratados do ponto de vista clínico, os problemas sociais e profissionais podem ser corrigidos ou evitados, independentemente de outras medidas especializadas que possam ser postas em prática.The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy is studied. Only barbiturates, hydantoin, primidone and trimethadione were administered to the patients, isolated or in association. The school, house keeper and professional activities were considered in the investigation. The socio-professional follow-up was investigated regarding to clinic manifestations, time of disease, frequency of seizures and electroencephalographic pattern. The results, analysed in percentage, led the author to the conclusion that in most epileptic patients, adequately controlled with drugs, the social and the professional problems can be avoided.

  5. Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

    Science.gov (United States)

    Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

    2017-01-01

    We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by

  6. Prophylactic drug management for febrile seizures in children

    Directory of Open Access Journals (Sweden)

    Martin Offringa

    Full Text Available BACKGROUND Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. OBJECTIVE To evaluate the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures. METHODS Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL (The Cochrane Library 2011. Issue 3; MEDLINE (1966 to May 2011; EMBASE (1966 to May 2011; Database of Abstracts of Reviews of Effectiveness (DARE (May 2011. No language restrictions were imposed. We also contacted researchers in the field to identify continuing or unpublished studies. Selection criteria: Trials using randomized or quasi-randomized patient allocation that compared the use of antiepileptic or antipyretic agents with each other, placebo or no treatment. Data collection and analysis: Two review authors (RN and MO independently applied pre-defined criteria to select trials for inclusion and extracted the pre-defined relevant data, recording methods for randomization, blinding and exclusions. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. The presence of publication bias was assessed using funnel plots. MAIN RESULTS Thirty-six articles describing 26 randomized trials with 2740 randomized participants were included. Thirteen interventions of continuous or intermittent prophylaxis and their control treatments were analyzed. Methodological quality was moderate to poor in most studies. We could not do a meta-analysis for 8 of the 13 comparisons due to insufficient numbers of trials. No significant benefit for valproate, pyridoxine

  7. [Diagnosis and management of de novo epilepsy].

    Science.gov (United States)

    Louise, Tyvaert

    2018-03-01

    The diagnosis of de novo epilepsy is complex. An accurate diagnostic approach has to be followed based on specific key steps. Epileptic seizure or non-epileptic malaise: risk of diagnosis error around 20%. Facing a first unprovoked seizure, the practitioner has to know the risk factors specifically linked to an increase risk of seizure recurrence. In presence of these factors, an antiepileptic drug would be indicated. The first antiepileptic drug has to be highly selected according to the epilepsy type and causes but also to the patient characteristics (sex, age, comorbidities, associated drugs, profession, and way of life…) An exhaustive patient Education needs to support the first antiepileptic drug prescription: (sleep and nutritional advices, benefit of observance, antiepileptic drugs features and side effects, follow-up, prognosis…) A regular follow-up is essential to control the observance, tolerability and efficacy of the antiepileptic drug, and to control also the good acceptance of the disease. A systematic research of common comorbidities may be also performed. Electroencephalogram and antiepileptic drugs levels are unnecessary in the classical follow up of known epileptic patients (except specific cases). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Divergence Palsy due to Divalproex and Oxcarbazepine.

    Science.gov (United States)

    Bouffard, Marc Albert; Caplan, Louis R; Torun, Nurhan

    This case series is the first to describe divergence palsy as an adverse effect of antiepileptic drug use. Diplopia is a common adverse effect of antiepileptic drugs, but no explanatory motility deficit has ever been reported. We present 2 patients, 1 on oxcarbazepine and 1 on divalproex, each with a normal examination result between spells and divergency palsy when symptomatic. Discontinuation of the antiepileptic medication led to resolution of the episodes in both cases. Rechallenge with the offending agent after washout in one patient resulted in recurrence of diplopia and divergence palsy, both resolving after subsequent withdrawal of the antiepileptic. Antiepileptic drugs may cause divergence palsy.

  9. Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

    Science.gov (United States)

    Emmerton, Lynne; Rizk, Mariam F S; Bedford, Graham; Lalor, Daniel

    2015-02-01

    Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports. © 2014 John Wiley & Sons, Ltd.

  10. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India.

    Science.gov (United States)

    Thomas, Sanjeev V; Jose, Manna; Divakaran, Srividya; Sankara Sarma, Prabhakaran

    2017-02-01

    Kerala Registry of Epilepsy and Pregnancy had been prospectively evaluating the reproductive issues of women with epilepsy since April 1998. This analysis aimed to estimate the relative risk of major congenital malformations (MCM) to the registrants. All pregnancies with known outcome in this register until December 2013 were included. Malformation status was evaluated by antenatal ultrasonography, physical examination at birth, echocardiography, and abdomen ultrasonography at 3 months of age and a final review at 1 year of age. There were 1,688 fetuses (singlets 1,643, twins 21, and triplet 1) resulting in 1,622 live births. All were born to women of Asian origin living in South India. The MCM rate for all live births was 6.84% (95% confidence interval [CI] 5.71-8.18) and for all pregnancy outcomes including fetal loss was 7.11% (95% CI 5.98-8.44). The MCM rates (mean with 95% CI) for exposed group were 6.4% (5.03-8.03) for monotherapy and 9.9% (7.37-13.13) for polytherapy; internal control group (women with epilepsy [WWE] not on antiepileptic drugs [AEDs] in first trimester) 5.6% (3.34-9.11), external control group (women without epilepsy or AED exposure in first trimester) 3.45% (1.94-6.07). Valproate monotherapy group had a dose-dependent relative risk for MCM of 2.6 (95% CI 1.30-5.20) compared to the external control group. The preliminary data on MCM rate for the nine total clobazam monotherapy (22.2%; 95% CI 6.2-54.7) signals increased risk that needs further validation on larger sample size. There was no association between MCM rate and maternal socioeconomic status, epilepsy syndrome, or use of folic acid in first trimester. This dataset from South India confirms the increased risk of MCM with exposure to AEDs, particularly polytherapy. A dose-dependent increased risk was observed with valproate. The increased risk associated with clobazam monotherapy is an important signal that needs to be confirmed in a larger sample. Wiley Periodicals, Inc. © 2017

  11. 33 CFR 95.020 - Standard for under the influence of alcohol or a dangerous drug.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or a dangerous drug. 95.020 Section 95.020 Navigation and Navigable Waters COAST GUARD... ALCOHOL OR A DANGEROUS DRUG § 95.020 Standard for under the influence of alcohol or a dangerous drug. An individual is under the influence of alcohol or a dangerous drug when: (a) The individual is operating a...

  12. Do the recommended standards for in vitro biopharmaceutic classification of drug permeability meet the "passive transport" criterion for biowaivers?

    Science.gov (United States)

    Žakelj, Simon; Berginc, Katja; Roškar, Robert; Kraljič, Bor; Kristl, Albin

    2013-01-01

    BCS based biowaivers are recognized by major regulatory agencies. An application for a biowaiver can be supported by or even based on "in vitro" measurements of drug permeability. However, guidelines limit the application of biowaivers to drug substances that are transported only by passive mechanisms. Regarding published permeability data as well as measurements obtained in our institution, one can rarely observe drug substances that conform to this very strict criterion. Therefore, we measured the apparent permeability coefficients of 13 drugs recommended by FDA's Guidance to be used as standards for "in vitro" permeability classification. The asymmetry of permeability data determined for both directions (mucosal-to-serosal and serosalto- mucosal) through the rat small intestine revealed significant active transport for four out of the nine high-permeability standards and for all four low-permeability standard drugs. As could be expected, this asymmetry was abolished at 4°C on rat intestine. The permeability of all nine high-permeability, but none of the low permeability standards, was also much lower when measured with intestinal tissue, Caco-2 cell monolayers or artificial membranes at 4°C compared to standard conditions (37°C). Additionally, concurrent testing of several standard drugs revealed that membrane transport can be affected by the use of internal permeability standards. The implications of the results are discussed regarding the regulatory aspects of biopharmaceutical classification, good practice in drug permeability evaluation and regarding the general relevance of transport proteins with broad specificity in drug absorption.

  13. The effects of antiepileptic inducers in neuropsychopharmacology, a neglected issue. Part I: A summary of the current state for clinicians.

    Science.gov (United States)

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. This is part i of a comprehensive review on antiepileptic drug (AED) inducers using both mechanistic pharmacological and evidence-based medicine to provide practical recommendations to neurologists and psychiatrists concerning how to control for them. Carbamazepine, phenobarbital and phenytoin, are clinically relevant AED inducers; correction factors were calculated for studied induced drugs. These correction factors are rough simplifications for orienting clinicians, since there is great variability in the population regarding inductive effects. As new information is published, the correction factors may need to be modified. Some of the correction factors are so high that the drugs (e.g., bupropion, quetiapine or lurasidone) should not co-prescribed with potent inducers. Clobazam, eslicarbazepine, felbamate, lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin and valproic acid are grouped as mild inducers which may (i)be inducers only in high doses; (ii)frequently combine with inhibitory properties; and (iii)take months to reach maximum effects or de-induction, definitively longer than the potent inducers. Potent inducers, definitively, and mild inducers, possibly, have relevant effects in the endogenous metabolism of (i)sexual hormones, (ii) vitamin D, (iii)thyroid hormones, (iv)lipid metabolism, and (v)folic acid. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

  14. Lack of cross-reactivity of Ambien (zolpidem) with drugs in standard urine drug screens.

    Science.gov (United States)

    Piergies, A A; Sainati, S; Roth-Schechter, B

    1997-04-01

    To determine in healthy volunteers (men and women; 18 to 40 years old) the potential cross-reactivity of Ambien (zolpidem) and/or its metabolites with drugs that are screened by the Syva EMIT II and the Abbott ADx urine drug screens assays. Open-label, fixed-treatment sequence of 1 night each of treatment with zolpidem (10 mg) and temazepam (15 mg). Clinical Pharmacology Unit within a teaching hospital. Over a 24-hour period, presence or absence of positive results on the Syva EMIT II or the Abbott ADx urine drug assay system, each performed at two different laboratory assay sites. Following ingestion of zolpidem, no subject had any positive response in either laboratory to the Syva EMIT II or the Abbott ADx urine drug screen assays at 0, 4, 8, 12, and 24 hours postdose. During the same time period, all subjects had measurable zolpidem plasma concentrations at 1.5 and 8 hours postdose, with mean concentrations of 115.2 ng/mL and 30.1 ng/mL, respectively (in agreement with its half-life of 2.5 hours). The positive response rate at 10 hours after ingestion of Restoril (temazepam) among the four laboratory/assay combinations ranged from 36.8% to 73.7%, a range that is within the reported response rates for these tests. These data indicate that zolpidem will not cross-react in standard urine drug screens with benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines.

  15. Clarithromycine-Induced Ventricular Tachycardia in a Geriatric Patient Using Multiple Drugs

    Directory of Open Access Journals (Sweden)

    Gulsah Karaoren

    2016-07-01

    Full Text Available Long QT syndrome is a cardiac repolarization disorder, which can be either idiopathic or congenital, and cause sudden cardiac death. The iatrogenic form is generally associated with drugs or electrolyte imbalance. Although prolonged QT interval is frequently seen due to antiarrhythmic agents, it can also be seen with antibiotics or anti-epileptics. Adverse drug interaction can manifest in several clinicopathological forms in elder individuals. In such cases, potential adverse effects of drugs used should be taken into consideration before prescribing additional drugs. Here, we present a case of clarithromycine-induced ventricular arrhythmia accompanied by QT prolongation on the third day of therapy, and the subsequent therapeutic approach, in a 91-year-old man. The patient was taking multiple drugs due to comorbid conditions and was prescribed clarithromycine therapy in the intensive care unit.

  16. [Neonatal risks of drugs exposure at the end of pregnancy].

    Science.gov (United States)

    Autret-Leca, Elisabeth; Cissoko, Hawaré; Jonville-Béra, Annie Pierre

    2011-01-01

    Foetal drugs exposure consequences depend according to the drug involved and to the length of the exposure which in the sum of length of treatment and of drug elimination (5 half life). Decisions are based upon risk evaluation and are a compromise between a risk banalisation and an excess of carefully. We described risks management for drugs used for a disease due to the pregnancy (glucocorticoïdes, antibiotics) then for drugs used for a chronic disease often preceding the pregnancy (non steroidal anti-inflammatory, serotonin recapture inhibitors, benzodiazepines, antiepileptics, conversion enzyme inhibitors/renine angiotensine antagonists, betabloquants). We also present the elements to take in account for the best drug choice at the end of pregnancy and/or for an adapted advice if the drug has been already taken: the drug itself (pharmacological effects, kinetics in neonate, toxicity marker, risk detection tool), drug amount possibly received by the neonate and literature data about neonatal manifestations due to the drug. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  17. Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

    Science.gov (United States)

    Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

    2018-04-25

    Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Registries Help Moms Measure Medication Risks

    Science.gov (United States)

    ... in the case of the North American Antiepileptic Drug Pregnancy Registry, which studies the effects of drugs for ... is taking. For example, the North American Antiepileptic Drug Pregnancy Registry website lists more than 30 medications being ...

  19. Obstetric risks for women with epilepsy during pregnancy.

    Science.gov (United States)

    Kaplan, Peter W; Norwitz, Errol R; Ben-Menachem, Elinor; Pennell, Page B; Druzin, Maurice; Robinson, Julian N; Gordon, Jacki C

    2007-11-01

    Women with epilepsy (WWE) face particular challenges during their pregnancy. Among the several obstetric issues for which there is some concern and the need for further investigation are: the effects of seizures, epilepsy, and antiepileptic drugs on pregnancy outcome and, conversely, the effects of pregnancy and hormonal neurotransmitters on seizure control and antiepileptic drug metabolism. Obstetric concerns include preclampsia/eclampsia, preterm delivery, placental abruption, spontaneous abortion, stillbirth, and small-for-date babies in WWE whether or not they are taking antiepileptic drugs. The role of nutritional health elements, including body mass index, caloric and protein intake, vitamins and iron, and phytoestrogens, warrants further study. During the course of obstetric management, there is a need for a fuller understanding by neurologists of the risk-benefit calculations for various types and frequencies of fetal imaging, including CT, MRI, and ultrasound, as well as for the screening standards of care. As part of the Health Outcomes in Pregnancy and Epilepsy (HOPE) project, this expert panel provides a brief overview of these concerns, offers some approaches to management, and outlines potential areas for further investigation. More detailed information and guidelines are available elsewhere.

  20. Czech Teratology Information Service: comparison of treatments by psychotropic and antiepileptic drugs.

    Science.gov (United States)

    Manáková, Eva; Hubicková-Heringová, Lucie; Jelínek, Richard

    2006-12-01

    Care, treatment and follow-up in psychiatric and epileptic pregnant women were compared with women inquiring Czech Teratology Information Service (CZTIS) due to other exposure to drugs during pregnancy. Data were collected by CZTIS, member of European Network of Teratology Information Services from 1996. Exposed groups were compared with pregnant women exposed to drugs which were not classified as major teratogens or hyperthermia. Groups do not vary in age, reproductive history and other parameters. We observed higher frequency of miscarriage and voluntary termination of pregnancy in the group of psychiatric patients. The number of malformation in prospective follow-up cases was lower than in control group. Chronic diseases as epilepsy or psychiatric disorders have to be treated during pregnancy. Women should obtain accurate information about possible risk before pregnancy. Co-operation is needed in these cases. Physicians should keep in mind that appropriate information is to be given to the patient according to her disease, education and comprehension of the problem. If there is any doubt they should organize help for their patients.

  1. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

    International Nuclear Information System (INIS)

    2016-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  2. CNS Depressant and Antiepileptic Activities of the Methanol Extract of the Leaves of Ipomoea Aquatica Forsk

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Sivaraman

    2010-01-01

    Full Text Available The central nervous system (CNS depressant and antiepileptic activities of the methanol extract of the leaves of Ipomoea aquatica Forsk (IAF were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behavior for sedation tests and strychnine, picrotoxin and pentylenetetrazole-induced convulsions in mice. IAF (200 and 400 mg/kg, p.o., like chlorpromazine HCl (1 mg/kg, i.m., produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behavior. IAF (200 and 400 mg/kg produced dose-dependent and significant increases in onset to clonic and tonic convulsions and at 400 mg/kg, showed complete protection against seizures induced by strychnine and picrotoxin but not with pentylenetetrazole. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity. These results suggest that potentially antiepileptic compounds are present in leaf extract of IAF that deserve the study of their identity and mechanism of action.

  3. Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

    Science.gov (United States)

    Mintzer, Scott; Wechsler, Robert T; Rogin, Joanne B; Gidal, Barry E; Schwab, Matthias; Ben-Menachem, Elinor; Carreño, Mar; da Silva, Patrício Soares; Moreira, Joana; Li, Yan; Blum, David; Grinnell, Todd

    2018-03-01

    To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (ESL 1200 mg QD (ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Development of a standardized, citywide process for managing smart-pump drug libraries.

    Science.gov (United States)

    Walroth, Todd A; Smallwood, Shannon; Arthur, Karen; Vance, Betsy; Washington, Alana; Staublin, Therese; Haslar, Tammy; Reddan, Jennifer G; Fuller, James

    2018-06-15

    Development and implementation of an interprofessional consensus-driven process for review and optimization of smart-pump drug libraries and dosing limits are described. The Indianapolis Coalition for Patient Safety (ICPS), which represents 6 Indianapolis-area health systems, identified an opportunity to reduce clinically insignificant alerts that smart infusion pumps present to end users. Through a consensus-driven process, ICPS aimed to identify best practices to implement at individual hospitals in order to establish specific action items for smart-pump drug library optimization. A work group of pharmacists, nurses, and industrial engineers met to evaluate variability within and lack of scrutiny of smart-pump drug libraries. The work group used Lean Six Sigma methodologies to generate a list of key needs and barriers to be addressed in process standardization. The group reviewed targets for smart-pump drug library optimization, including dosing limits, types of alerts reviewed, policies, and safety best practices. The work group also analyzed existing processes at each site to develop a final consensus statement outlining a model process for reviewing alerts and managing smart-pump data. Analysis of the total number of alerts per device across ICPS-affiliated health systems over a 4-year period indicated a 50% decrease (from 7.2 to 3.6 alerts per device per month) after implementation of the model by ICPS member organizations. Through implementation of a standardized, consensus-driven process for smart-pump drug library optimization, ICPS member health systems reduced clinically insignificant smart-pump alerts. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  5. DILI (drug induced liver injury in a 9-month-old infant: a rare case of phenobarbital-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Paola Pinna

    2013-04-01

    Full Text Available Phenobarbital is one of the most commonly prescribed antiepileptic drugs in childhood, but it can rarely cause serious adverse effects, such as hepatotoxicity that includes a broad clinical spectrum (from isolate hypertransaminasemia to acute liver failure. We describe a case of DILI in a 9-month-old infant caused by chronic therapy with phenobarbital.

  6. Detection of systemic hypersensitivity to drugs using standard guinea pig assays.

    Science.gov (United States)

    Weaver, James L; Staten, David; Swann, Joslyn; Armstrong, George; Bates, Melissa; Hastings, Kenneth L

    2003-12-01

    The most commonly used assays designed to detect either skin or systemic immune-based hypersensitivity reactions are those using guinea pigs (GP). We obtained data from various FDA records to evaluate the correlation between GP assay results and reported post-marketing systemic hypersensitivity reactions. We examined the new drug application (NDA) reviews of approved drugs for the results of GP assays. Post-marketing human data were extracted from the FDA adverse event reporting system (AERS). Drug usage data were obtained from a commercial database maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between 1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were found to have positive results in at least one GP assay. Simple reporting index (RI) values for systemic hypersensitivity reactions were calculated from AERS data and usage to produce the index of adverse event reports per million shipping units of drug. A variety of definitions of positive human response were examined. A statistically significant association was seen for rash between post-marketing and clinical trials adverse event reports. No statistically significant associations between human data and GP test results were observed. These data suggest that standard GP assays have limited ability to predict human systemic hypersensitivity potential for pharmaceuticals.

  7. Molecular Docking Study, Green Synthesis and Pharmacological Evaluation of 1,3,4-thiadiazole Derivatives as Potential Antiepileptic Agents

    Czech Academy of Sciences Publication Activity Database

    Sahoo, B. M.; Dinda, S. C.; Kumar, B. V. V. R.; Panda, J. R.; Brahmkshatriya, Pathik

    2013-01-01

    Roč. 13, č. 14 (2013), s. 2076-2081 ISSN 1389-5575 Institutional support: RVO:61388963 Keywords : antiepileptic activity * docking study * epilepsy * green synthesis * neurotoxicity * thiadiazole Subject RIV: CC - Organic Chemistry Impact factor: 3.186, year: 2013

  8. Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

    Science.gov (United States)

    Germovsek, Eva; Barker, Charlotte I S; Sharland, Mike; Standing, Joseph F

    2018-04-19

    Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies.

  9. Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

    Directory of Open Access Journals (Sweden)

    Stimson Gerry V

    2006-03-01

    Full Text Available Abstract Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs. Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups

  10. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Hallas, Jesper

    2009-01-01

    Database (OPED) for the period of 1 August 1990-31 December 2006, and diagnoses from the County Hospital register for the period of 1994-2006 to perform sequence symmetry analysis. The method assesses the distribution of disease entities and prescription of other drugs (ODs), before and after initiation...

  11. Toxic epidermal necrolysis due to concomitant use of lamotrigine and valproic acid

    Directory of Open Access Journals (Sweden)

    Sukhjot Kaur

    2013-01-01

    Full Text Available Anti-epileptic drugs can be associated with a wide spectrum of cutaneous adverse reactions ranging from simple maculopapular rashes to more severe and life threatening reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis. These rashes are well documented with older antiepileptic drugs like phenytoin, phenobarbitone and carbamazapine. Lamotrigine is a newer, unrelated antiepileptic drug that causes skin rashes in 3-10% of new users. Higher starting dose or rapid escalation, concurrent treatment with valproic acid, and a previous history of a rash with other antiepileptic drugs are well recognized risk factors for lamotrigine related serious rashes. We report two patients with toxic epidermal necrolysis, resulting from concomitant use of lamotrigine and valproic acid. It is emphasized that clinicians adhere to the recommended dosage guidelines and adopt a slow dose titration when initiating treatment with lamotrigine.

  12. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  13. Evaluation of Homocysteine, Folic Acid and Vitamin B12 Levels among Egyptian Children with Idiopathic Epilepsy

    Directory of Open Access Journals (Sweden)

    Soha M. Abd El Dayem

    2014-03-01

    Conclusion: antiepileptic drugs might upset the homeostatic balance of Hcy and its cofactors and cause abnormalities of their serum levels. The duration of anti-epileptic drug treatment was related to decrease of folic acid and increase in homocysteine levels.

  14. [Salivary flow and psychoactive drug consumption in elderly people].

    Science.gov (United States)

    Cabrera, Marcos Aparecido Sarria; Mesas, Arthur Eumann; Rossato, Luiz Angelo; Andrade, Selma Maffei de

    2007-01-01

    To analyze the association between low saliva flow rates and the use of psychoactive drugs among the elderly. A cross-sectional study was carried out with 267 elderly people from 60 to 74 years of age who lived in a borough of the city of Londrina, Paraná State, Brazil. Individuals with high functional dependence or restricted to bed were excluded. Saliva flow rate was the dependent variable with values under the first tercile being considered as low flow rates (less than 0.44 ml/min). The continuous use of psychoactive drugs (antidepressant, antiepileptic, sedative, antipsychotic, hypnotic or sedative-hypnotic drugs) was the independent variable. Multivariate analysis was performed taking into account gender, age and smoking status. The majority of the elderly were women (80.5%), with a mean age of 66.5 years. Use of psychoactive drugs was observed among 31 elderly (11.6%). Mean saliva flow rate was 0.76 ml/min, lower among users of psychoactive drugs (0.67 ml/min). In the multivariate analysis, use of psychoactive drugs was associated with low saliva flow rates (psychoactive drugs and low saliva flow rates in this group of independent and non-institutionalized elderly. These conclusions stress the need of a rational use of these drugs, particularly among the elderly.

  15. What is the standard approach to assessment of an unprovoked seizure in an adult?: HONG KONG

    OpenAIRE

    Kwan, Patrick

    2012-01-01

    Since Hong Kong is highly urbanized and acute public hospitals have been established across the city, most patients with unprovoked seizures not already receiving antiepileptic drug (AED) therapy, particularly convulsive seizures, will be admitted as emergency for assessment. A thorough history is taken from the patient and any witnesses to the seizure. This includes the circumstance of the seizures, detailed symptoms and signs experienced by the patient and witnessed by others before, during...

  16. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  17. Antiepileptic drugs and intrauterine death

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    ) after prenatal AED exposure. Using EURAP data, we prospectively monitored pregnancies exposed to the 6 most common AED monotherapies and to polytherapy. Intrauterine death (spontaneous abortion and stillbirth combined) was the primary endpoint. RESULTS: Of 7,055 pregnancies exposed to monotherapy...... with lamotrigine (n = 1,910), carbamazepine (n = 1,713), valproic acid (n = 1,171), levetiracetam (n = 324), oxcarbazepine (n = 262), or phenobarbital (n = 260), and to polytherapy (n = 1,415), 632 ended in intrauterine deaths (592 spontaneous abortions and 40 stillbirths). Rates of intrauterine death were similar...... that the risk was greater with polytherapy vs monotherapy (risk ratio [RR] 1.38; 95% CI 1.14-1.66), parental history of MCMs (RR 1.92; 1.20-3.07), maternal age (RR 1.06; 1.04-1.07), and number of previous intrauterine deaths (RR 1.09; 1.00-1.19). The risk was greater with early enrollment and decreased...

  18. [Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

    Science.gov (United States)

    Sokić, D; Janković, S M

    1994-01-01

    Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

  19. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis

    Science.gov (United States)

    Veroniki, Areti Angeliki; Rios, Patricia; Cogo, Elise; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

    2017-01-01

    Objectives Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. Design and setting Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. Participants 29 cohort studies including 5100 infants/children. Interventions Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. Primary and secondary outcome measures Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes. Results The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8

  20. Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lu Ban

    Full Text Available Antenatal antiepileptic drug (AED use has been found to be associated with increased major congenital anomaly (CA risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily folic acid supplementation is still unclear.We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception.CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21. Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46-4.74 and aOR 2.01,1.12-3.59 respectively and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group; however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy.Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be

  1. What does the U.S. Medicare administrative claims database tell us about initial antiepileptic drug treatment for older adults with new-onset epilepsy?

    Science.gov (United States)

    Martin, Roy C; Faught, Edward; Szaflarski, Jerzy P; Richman, Joshua; Funkhouser, Ellen; Piper, Kendra; Juarez, Lucia; Dai, Chen; Pisu, Maria

    2017-04-01

    Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs (AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries. We conducted retrospective analyses of 2008-2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision (ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment (QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [LIS], and ZIP code level poverty) factors. Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [AI/AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted

  2. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  3. Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

    Science.gov (United States)

    Andrade, Paulo Henrique Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros

    2017-01-01

    The present study aims to identify the risk factors for adverse drug reactions (ADR) in pediatric inpatients. A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used. A total of 173 children (208 admissions) and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%). In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56) were identified risk factors for ADR. We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

  4. Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Santos Andrade

    Full Text Available The present study aims to identify the risk factors for adverse drug reactions (ADR in pediatric inpatients.A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used.A total of 173 children (208 admissions and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%. In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR 2.44; 95% confidence interval (CI 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54, antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98 and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56 were identified risk factors for ADR.We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

  5. Pattern of drug eruptions in a tertiary care hospital

    International Nuclear Information System (INIS)

    Tahir, Z.; Nadeem, N.; Aman, S.; Kazmi, A.H.

    2013-01-01

    Background: An adverse drug reaction is unintentional which occurs at doses used for prophylaxis, diagnosis or treatment. Objectives: To determine the frequency of various cutaneous drug eruptions that occur in patients in a tertiary care hospital setting. Patients and Methods: All patients with cutaneous drug eruptions seen at the Dermatology Department of Mayo Hospital, Lahore, over 6 months were enrolled and the pattern of drug eruptions like urticaria, angioedema, fixed drug eruption, maculopapular rash, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis etc. were recorded, along with drugs that caused it. Results:A total of 160 patients (86 males, 74 females) were included in the study. Mean age of patients was 30.7+-15.4 years. Major eruptions were fixed drug eruption (21.3%) followed by urticaria without angioedema (10%), maculopapular rash (9.3%), lichenoid drug eruption (8.7%), acneiform drug eruption (7.5%), Stevens-Johnson syndrome (6.9%), vesiculobullous eruption (5.6%), erythema multiforme and eczematous eruption (5% each). Common drugs causing eruptions were sulfonamides (16.3%), followed by NSAIDs (14.4%), herbal and homeopathic medications (12.5%), penicillins (9.3%), tetracyclines (8.7%), antituberculous drugs, cephalosporins and antiepileptics (6.3% each). Conclusion: Fixed drug eruption and urticaria without angioedema were commonest eruptions while, sulfonamides and NSAIDs were the major causative drugs. Policy message: Reporting of adverse drug reactions is not done in Pakistan and needs to be done in each hospital. (author)

  6. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  7. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  8. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

  9. Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

    Science.gov (United States)

    Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (ptextbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education. PMID:25250889

  10. How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?

    Science.gov (United States)

    Yuen, Eunice S M; Sims, John R

    2014-06-01

    Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. ADEpedia: a scalable and standardized knowledge base of Adverse Drug Events using semantic web technology.

    Science.gov (United States)

    Jiang, Guoqian; Solbrig, Harold R; Chute, Christopher G

    2011-01-01

    A source of semantically coded Adverse Drug Event (ADE) data can be useful for identifying common phenotypes related to ADEs. We proposed a comprehensive framework for building a standardized ADE knowledge base (called ADEpedia) through combining ontology-based approach with semantic web technology. The framework comprises four primary modules: 1) an XML2RDF transformation module; 2) a data normalization module based on NCBO Open Biomedical Annotator; 3) a RDF store based persistence module; and 4) a front-end module based on a Semantic Wiki for the review and curation. A prototype is successfully implemented to demonstrate the capability of the system to integrate multiple drug data and ontology resources and open web services for the ADE data standardization. A preliminary evaluation is performed to demonstrate the usefulness of the system, including the performance of the NCBO annotator. In conclusion, the semantic web technology provides a highly scalable framework for ADE data source integration and standard query service.

  12. [The original nootropic and neuroprotective drug noopept potentiates the anticonvulsant activity of valproate in mice].

    Science.gov (United States)

    Kravchenko, E V; Ponteleeva, I V; Trofimov, S S; Lapa, V I; Ostrovskaia, R U; Voronina, T A

    2009-01-01

    The influence of the original dipeptide drug noopept, known to possess nootrope, neuroprotector, and anxiolytic properties, on the anticonvulsant activity of the antiepileptic drug valproate has been studied on the model of corazole-induced convulsions in mice. Neither a single administration of noopept (0.5 mg/kg, i.p.) nor its repeated introduction in 10 or 35 days enhanced the convulsant effect of corazole, which is evidence that noopept alone does not possess anticonvulsant properties. Prolonged (five weeks) preliminary administration of noopept enhanced the anticonvulsant activity of valproate. This result justifies the joint chronic administration of noopept in combination with valproate in order to potentiate the anticonvulsant effect of the latter drug. In addition, the administration of noopept favorably influences the cognitive functions and suppresses the development of neurodegenerative processes.

  13. [Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

    Science.gov (United States)

    Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

    2012-01-01

    Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

  14. Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

    Science.gov (United States)

    Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

    2016-01-01

    Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.

  15. Oxcabazepine (®Trileptal in Anti-Epileptic Polytherapy

    Directory of Open Access Journals (Sweden)

    Peder Klosterskov Jensen

    1990-01-01

    Full Text Available The anti-epileptic activity of oxcarbazepine (OXC was compared with that of carbamazepine (CBZ and the primary active metabolite of OXC, a monohydroxy derivative (MHD. Altogether 255 patients receiving either OXC or MHD (192 and 63 patients respectively were included in the analysis of efficacy. Out of these 255 patients a total of 40 were children. The duration of treatment varied between 8 and 24weeks. The daily dose of OXC or MHD varied between 600 and 5400 mg (in children 600–2400 mg. Out of five studies two were double-blind controlled studies (including a total of 105 patients whereas the remaining three were open studies. The results of these studies indicate that, in adults with epilepsy, there is no statistically significant difference in overall seizure frequency between CBZ and OXC. In one double-blind study the number of generalized tonic-clonic seizures was significantly less frequent during treatment with OXC than with CBZ. No statistically significant difference with regard to side-effects was observed between OXC and CBZ. The results in children with epilepsy show a statistically significant difference in seizure frequency in favour of OXC, in comparison with CBZ. Overall, the polytherapy studies in adults and children support the effectiveness and safety of oxcarbazepine.

  16. Effect of the new antiepileptic drug retigabine in a rodent model of mania

    DEFF Research Database (Denmark)

    Dencker, Ditte; Dias, Rebecca; Pedersen, Mette Lund

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were...

  17. Use of opium as antiepileptic in patient with frontal lobe epilepsy: A case report

    Directory of Open Access Journals (Sweden)

    Naresh Nebhinani

    2015-01-01

    Full Text Available Frontal lobe epilepsy (FLE manifests with brief, nocturnal seizures arising in the frontal lobe along with unusual behavioral symptoms or postures, frequently misdiagnosed as a psychogenic nonepileptic seizure (PNES or a sleep disorder. Ancient literature has rarely mentioned the antiepileptic effect of opium or different opioids. Here we are presenting a case with FLE, though initially diagnosed PNES, who had significant relief in his symptoms on using opium, and this led to opium dependence. Index case further emphasizes concern and caution as misdiagnosis of FLE may lead to substance dependenc.

  18. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Directory of Open Access Journals (Sweden)

    Jona Kräenbring

    Full Text Available The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001. Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001 and highest in the category "indication" (91.3% ± 2.0% when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

  19. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Science.gov (United States)

    Kräenbring, Jona; Monzon Penza, Tika; Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001). Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001) and highest in the category "indication" (91.3% ± 2.0%) when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

  20. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

    Directory of Open Access Journals (Sweden)

    Shanshan Liu

    2018-01-01

    Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

  1. EFFICACY OF RUFINAMIDE IN THE TREATMENT OF DRUG-RESISTANT FOCAL EPILEPSIES IN PAEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    I. O. Shchederkina

    2016-01-01

    Full Text Available Among drug-resistant epilepsies, epileptic syndromes, characterized by combination of several types of seizures, are considered to be the most difficult in terms of treatment. Lennox–Gastaut syndrome is one of them. It manifests with polymorphic seizures (tonic axial, myatonic, atypical absence seizures, status epilepticus of minor motor seizures, myoclonic, generalized convulsive, and focal seizures. This is a heterogeneous disease, represented by a complex of clinical and electroencephalographic manifestations with various etiology. Current review is devoted to a novel antiepileptic drug rufinamide, which has a new mechanism of action. The drug has been registered in Russia in 2015. The authors also describe their own experience of rufinamide usage in the treatment of drug-resistant focal epilepsy as a part of multicomponent therapy for polymorphic seizures. One patient achieved clinical remission for 16 months; the second one had more than 50 % decrease in seizures frequency with a remission of drop-attacks.

  2. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  3. Integrity, standards, and QC-related issues with big data in pre-clinical drug discovery.

    Science.gov (United States)

    Brothers, John F; Ung, Matthew; Escalante-Chong, Renan; Ross, Jermaine; Zhang, Jenny; Cha, Yoonjeong; Lysaght, Andrew; Funt, Jason; Kusko, Rebecca

    2018-06-01

    The tremendous expansion of data analytics and public and private big datasets presents an important opportunity for pre-clinical drug discovery and development. In the field of life sciences, the growth of genetic, genomic, transcriptomic and proteomic data is partly driven by a rapid decline in experimental costs as biotechnology improves throughput, scalability, and speed. Yet far too many researchers tend to underestimate the challenges and consequences involving data integrity and quality standards. Given the effect of data integrity on scientific interpretation, these issues have significant implications during preclinical drug development. We describe standardized approaches for maximizing the utility of publicly available or privately generated biological data and address some of the common pitfalls. We also discuss the increasing interest to integrate and interpret cross-platform data. Principles outlined here should serve as a useful broad guide for existing analytical practices and pipelines and as a tool for developing additional insights into therapeutics using big data. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Patients' perspectives on antiepileptic medication: relationships between beliefs about medicines and adherence among patients with epilepsy in UK primary care.

    Science.gov (United States)

    Chapman, S C E; Horne, R; Chater, A; Hukins, D; Smithson, W H

    2014-02-01

    Nonadherence to antiepileptic drugs (AEDs) can result in suboptimal outcomes for patients. This study aimed to assess the utility of a theory-based approach to understanding patient perspectives on AEDs and adherence. Patients with epilepsy, identified by a GP case note review, were mailed validated questionnaires assessing their perceptions of AEDs and their adherence to them. Most (84.9%) of the 398 AED-treated respondents accepted the necessity of AEDs, but over half expressed doubts, with 55% disagreeing or uncertain about the statement 'I would prefer to take epilepsy medication than risk a seizure'. Over a third (36.4%) expressed strong concerns about the potential negative effects of AEDs. We used self-report and medication possession ratio to classify 36.4% of patients as nonadherent. Nonadherence was related to beliefs about medicines and implicit attitudes toward AEDs (pbeliefs about pharmaceuticals (BMQ General: General Harm, General Overuse, and General Benefit scales) and perceptions of personal sensitivity to medicines (PSM scale). We identified salient, adherence-related beliefs about AEDs. Patient-centered interventions to support medicine optimization for people with epilepsy should take account of these beliefs. © 2013.

  5. The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

    Science.gov (United States)

    Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

    2007-12-01

    To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

  6. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    Science.gov (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  7. Food intake and antiepileptic drugs: evidence for a role of GABA in circadian time keeping.

    Science.gov (United States)

    Rietveld, W J; van Schravendijk, K

    1987-01-01

    Long-term application of sodium-valproate was studied while recording food intake of rats. It was found that sodium valproate was able to decrease the period length of free-running circadian rhythmicity. After withdrawal of the drug, the period length returned to the predrug values.

  8. An Update on Drug-induced Liver Injury.

    Science.gov (United States)

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  9. Papel de la monoterapia con nuevos fármacos antiepilépticos en el tratamiento de la epilepsia infantil Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Ignacio Valencia

    2009-01-01

    Full Text Available En este trabajo se revisa la información actual sobre el uso de los nuevos fármacos antiepilépticos (FAEs en monoterapia en niños, resaltando nuestra experiencia personal. Específicamente, se incluyen los siguientes FAEs: lamotrigina (Lamictal®, topiramato (Topamax®, zonisamida (Zonegran®, levetiracetam (Keppra®, y oxcarbacepina (Trileptal®. Todos estos FAEs tienen un amplio espectro de acción en el tratamiento de crisis epilépticas parciales y generalizadas, excepto la oxcarbacepina, que es eficaz exclusivamente en crisis parciales. No está claro si la monoterapia con estos FAEs, en comparación con los FAEs clásicos (fenobarbital, fenitoína, carbamacepina, valproato sódico, proporciona una mayor eficacia y/o causa menos efectos secundarios y, si por lo tanto, mejora significativamente la calidad de vida de los niños con epilepsia. Se necesitan más estudios para poder contestar estas preguntas.In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal®, topiramate (Topamax®, zonisamide (Zonegran®, levetiracetam (Keppra®, and oxcarbazepine (Trileptal®. All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

  10. Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

    Science.gov (United States)

    Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

    2017-07-01

    We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation. © The Author 2017. Published by Oxford University Press on behalf of the American

  11. Valproic acid-induced hyperammonemic encephalopathy - a potentially fatal adverse drug reaction.

    Science.gov (United States)

    Sousa, Carla

    2013-12-01

    A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid. A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10 days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15 ml twice daily, metronidazole 250 mg four times daily and L-carnitine 1 g twice daily. Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient's treatment. Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment.

  12. Pregnancy in epileptic patients: comparison between well-established therapeutic strategies and opportunities coming from new drugs

    Directory of Open Access Journals (Sweden)

    Francesca Pizzo

    2013-12-01

    Full Text Available Treating women affected by epilepsy during pregnancy is challenging.  Clinicians have to consider both the teratogenic effects of Antiepileptic Drugs (AEDs and the risk of seizure recurrence. Pharmacokinetic changes during pregnancy are rapid and conspicuous so that the serum concentration of drugs can be modified and the effectiveness of AEDs cannot be guaranteed. The aim of this study is to evaluate the risk of Major Congenital Malformation (MCM associated with AEDs treatment during the first trimester of pregnancy. We collected data from 338 patients who contacted the Teratology Information Services of XXX University Hospital and we found that only the variable monotherapy vs politherapy had statistical significance for MCM. More studies are needed to assess the efficacy and safety of newer AEDs.

  13. The role of cannabinoids and endocannabinoid system in the treatment of epilepsy

    Directory of Open Access Journals (Sweden)

    Pędracka Monika

    2015-12-01

    Full Text Available Introduction. The treatment of epilepsy is still a major challenge. Despite the introduction of many new antiepileptic drugs, approximately 30% of patients still remain drug resistant. In the absence of a satisfactory therapy outcome, which is sometimes associated with numerous side effects, there is a need for new and effective drugs with low toxicity. Cannabinoids have been shown in preliminary animal model studies and in studies of patients with epilepsy to have antiepileptic activity.

  14. Diterpenes: Advances in Neurobiological Drug Research.

    Science.gov (United States)

    Islam, Md Torequl; da Silva, Claucenira Bandeira; de Alencar, Marcus Vinícius Oliveira Barros; Paz, Márcia Fernanda Correia Jardim; Almeida, Fernanda Regina de Castro; Melo-Cavalcante, Ana Amélia de Carvalho

    2016-06-01

    A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action-wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro-protection, anti-epileptic, anxiolytic, anti-Alzheimer's disease, anti-Parkinson's disease, anti-cerebral ischemia, anti-neuropathic pain, anti-neuro-inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Evidence based herbal drug standardization approach in coping with challenges of holistic management of diabetes: a dreadful lifestyle disorder of 21st century.

    Science.gov (United States)

    Chawla, Raman; Thakur, Pallavi; Chowdhry, Ayush; Jaiswal, Sarita; Sharma, Anamika; Goel, Rajeev; Sharma, Jyoti; Priyadarshi, Smruti Sagar; Kumar, Vinod; Sharma, Rakesh Kumar; Arora, Rajesh

    2013-07-04

    Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner.

  16. Drug-Induced Dental Caries: A Disproportionality Analysis Using Data from VigiBase.

    Science.gov (United States)

    de Campaigno, Emilie Patras; Kebir, Inès; Montastruc, Jean-Louis; Rueter, Manuela; Maret, Delphine; Lapeyre-Mestre, Maryse; Sallerin, Brigitte; Despas, Fabien

    2017-12-01

    Dental caries is defined as a pathological breakdown of the tooth. It is an infectious phenomenon involving a multifactorial aetiology. The impact of drugs on cariogenic risk has been poorly investigated. In this study, we identified drugs suspected to induce dental caries as adverse drug reactions (ADRs) and then studied a possible pathogenic mechanism for each drug that had a statistically significant disproportionality. We extracted individual case safety reports of dental caries associated with drugs from VigiBase ® (the World Health Organization global individual case safety report database). We calculated disproportionality for each drug with a reporting odds ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each drug that had a statistically significant disproportionality. In VigiBase ® , 5229 safety reports for dental caries concerning 733 drugs were identified. Among these drugs, 88 had a significant ROR, and for 65 of them (73.9%), no information about dental caries was found in the summaries of the product characteristics, the Micromedex ® DRUGDEX, or the Martindale databases. Regarding the pharmacological classes of drugs involved in dental caries, we identified bisphosphonates, atropinic drugs, antidepressants, corticoids, immunomodulating drugs, antipsychotics, antiepileptics, opioids and β 2 -adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%), bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%) and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the mechanism was unclear. We identified 88 drugs with a significant positive disproportionality for dental caries. Special attention has to be paid to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing hyperglycaemia.

  17. Clinical utility of adjunctive retigabine in partial onset seizures in adults

    Directory of Open Access Journals (Sweden)

    Rejdak K

    2012-01-01

    Full Text Available Konrad Rejdak1, Jarogniew J Luszczki2,3, Barbara Blaszczyk4, Roman Chwedorowicz5, Stanislaw J Czuczwar2,51Department of Neurology, Medical University of Lublin, Lublin, 2Department of Pathophysiology, Medical University of Lublin, Lublin, 3Isobolography Analysis Laboratory, Institute of Agricultural Medicine, Lublin, 4Faculty of Health Sciences, High School of Economics and Law, Kielce, 5Department of Physiopathology, Institute of Agricultural Medicine, Lublin, PolandAbstract: In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease.Keywords: antiepileptic drugs, epilepsy, seizure control

  18. Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment

    Science.gov (United States)

    Baek, Jung-Hyun; Seo, Young-Ho; Kim, Gun-Ha; Kim, Mi-Kyung

    2014-01-01

    Purpose This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents. Materials and Methods We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21±4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables. Results For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency. Conclusion The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs. PMID:24532512

  19. Association of Folic Acid Supplementation During Pregnancy With the Risk of Autistic Traits in Children Exposed to Antiepileptic Drugs In Utero.

    Science.gov (United States)

    Bjørk, Marte; Riedel, Bettina; Spigset, Olav; Veiby, Gyri; Kolstad, Eivind; Daltveit, Anne Kjersti; Gilhus, Nils Erik

    2018-02-01

    Strategies to prevent autism in children exposed to antiepileptic drugs (AEDs) during pregnancy are important. To explore whether folic acid supplementation and folate status in pregnancy are associated with reduced risk of autistic traits owing to in utero AED exposure. The population-based, prospective Norwegian Mother and Child Cohort Study approached Norwegian-speaking women attending routine ultrasonographic examinations from June 1999 through December 31, 2008 (163 844 of 277 702 women refused). No exclusion criteria were applied beyond language. Questionnaires during and after pregnancy, analysis of blood samples, and linkage to the Medical Birth Registry of Norway were performed. Children aged 18 to 36 months of women with available information on use of AEDs and of folic acid supplementation (n = 104 946) were included in the analysis from March 1, 2016, through June 13, 2017. Maternal folic acid supplementation 4 weeks before to 12 weeks after conception. Plasma folate concentration was analyzed at gestational weeks 17 to 19. Autistic traits were evaluated using the Modified Checklist for Autism in Toddlers and Social Communication Questionnaire. Odds ratios (ORs) for autistic traits in children by maternal use vs nonuse of folic acid supplements were adjusted for maternal health and socioeconomic factors. Folate concentrations and folic acid doses were associated with the degree of autistic traits. The overall mean (SD) age of the 104 946 mothers of participating children was 29.8 (4.6) years, with complete information available for analysis in 103 868. Mean (SD) age of women with epilepsy who received AED treatment was 29.4 (4.9); women with epilepsy who did not receive AED treatment, 29.1 (4.9); and without epilepsy, 29.8 (4.6) years. In the 335 children exposed to AEDs, the risk for autistic traits was significantly higher at 18 months of age (adjusted OR [AOR], 5.9; 95% CI, 2.2-15.8) and 36 months of age (AOR, 7.9; 95% CI, 2.5-24.9) when

  20. Drugs related to the etiology of molar incisor hypomineralization: A systematic review.

    Science.gov (United States)

    Serna, Clara; Vicente, Ascensión; Finke, Christian; Ortiz, Antonio J

    2016-02-01

    Molar incisor hypomineralization (MIH) is an idiopathic syndrome that has been associated with several etiologic factors. The authors' objective was to systematically review studies in which the investigators had studied how the etiology of MIH was related to medication intake. The search covered a period from January 1, 1965, to September 29, 2014. The search revealed 1,042 articles, to which the authors applied eligibility criteria and selected 20 studies for review. The authors considered 9 of the 20 studies to be high quality. The drugs used in these studies were chemotherapeutic drugs, antibiotics, asthma drugs, antiepileptic drugs, antiviral drugs, antifungal drugs, and antiparasitic drugs. Two reviewers independently performed risk-of-bias assessment and data extraction. The investigators of all of the studies had reported enamel defects, but only 2 sets of investigators had used the term "molar incisor hypomineralization." Owing to the different methodologies used by the investigators of the selected studies, the authors could not perform a meta-analysis of the study results. More well-designed prospective studies are needed to clarify the relationship between MIH and medication. It would be convenient to establish a preventive protocol in patients with a potential risk of developing MIH to avoid the complications that are characteristic of this disease. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

  1. Association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.

    Science.gov (United States)

    Stasiołek, Mariusz; Romanowicz, Hanna; Połatyńska, Katarzyna; Chamielec, Maciej; Skalski, Dominik; Makowska, Marianna; Smolarz, Beata

    2016-07-08

    Epilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children. C3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model. An association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases. Following the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

  2. Chemometrics: A new scenario in herbal drug standardization

    Directory of Open Access Journals (Sweden)

    Ankit Bansal

    2014-08-01

    Full Text Available Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency. Key words: Chemometrics, HELP, Herbal drugs, PCA, OPA

  3. P08.13 Pattern of care and outcome in elderly glioblastoma patients: a multicenter retrospective study on 151 patientsi from 3 hospitals in Lombardia

    Science.gov (United States)

    Silvani, A.; Rigamonti, A.; Imbesi, F.; Legnani, F.; Grimod, G.; Arienti, V.; Prone, V.; Soatti, C.; Fariselli, L.; Salmaggi, A.

    2016-01-01

    Abstract Pending the results of the 26062 EORTC trial, no standard of care exists for elderly patients with glioblastoma. Randomized controlled trials have provided evidence of a slight survival benefit for radiotherapy versus best supportive care (Keime-Guibert) and of lack of substantial benefit from single post-surgical treatment over each other. Treatment is still largely variable according to local practice. In this study we investigated the pattern of care and outcome in patients older than 65 diagnosed with glioblatoma in 3 hospitals in Lombardia and analyzed factors with impact on survival. 151 patients were included in this study, enrolled in Lecco Hospital, Niguarda Hospital and Neurooncology Unit of Fondazione IRCCS Istituto Neurologico Besta and undergoing surgery from 2004 to 2014. 91 were male, 60 female. Age range was 65 to 83, with a median value of 72. Concerning clinical variables, KPS was 70 or higher in 109 patients and lower in 42. 19 patients underwent biopsy, 14 partial resection and 118 total/subtotal resection as evaluated by the neurosurgeon. 114 patients were treated with radiotherapy and 97 with chemotherapy (all these 97 also received radiotherapy). 32 patients displayed seizures at disease onset. 22 patients did not receive antiepileptic treatment, while 129 were treated with antiepileptic drugs despite absence of seizures in 48. 40% of patients treated with antiepileptic drugs received enzyme-inducing drugs, 60% were treated with either VPA or levetiracetam. At disease progression, 22 patients received further treatment, including repeat surgery and/or second-line chemotherapy. In only 36 patients were molecular biology tests performed (IDH1 mutation). At univariate analysis, survival was longer in patients with higher KPS (p=0.02), those receiving partial/total surgery vs biopsy (p=0.03), those receiving total resection (p=0.003), those treated with radiotherapy (p<0.0001), chemotherapy (p<0.0001), those being treated at Istituto

  4. Effects of Marijuana on Ictal and Interictal EEG Activities in Idiopathic Generalized Epilepsy.

    Science.gov (United States)

    Sivakumar, Sanjeev; Zutshi, Deepti; Seraji-Bozorgzad, Navid; Shah, Aashit K

    2017-01-01

    Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series, and clinical trials. However, literature on their EEG effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy treated with cannabis. We blindly reviewed 3 long-term EEGs-a 24-hour study while only on antiepileptic drugs, a 72-hour EEG with Cannabis indica smoked on days 1 and 3 in addition to antiepileptic drugs, and a 48-hour EEG with combination C indica/sativa smoked on day 1 plus antiepileptic drugs. Generalized spike-wave discharges and diffuse paroxysmal fast activity were categorized as interictal and ictal, based on duration of less than 10 seconds or greater, respectively. Data from three studies concatenated into contiguous time series, with usage of marijuana modeled as time-dependent discrete variable while interictal and ictal events constituted dependent variables. Analysis of variance as initial test for significance followed by time series analysis using Generalized Autoregressive Conditional Heteroscedasticity model was performed. Statistical significance for lower interictal events (analysis of variance P = 0.001) was seen during C indica use, but not for C indica/sativa mixture (P = 0.629) or ictal events (P = 0.087). However, time series analysis revealed a significant inverse correlation between marijuana use, with interictal (P EEG data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use. Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing, are needed to validate our findings.

  5. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2016-01-01

    . With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical......Zeng et al.'s Ethics Review highlights some of the challenges associated with clinical research in China. They found that only a minority of published clinical trials of anti-dementia drugs reported that they fulfilled the basic ethical principles as outlined in the Declaration of Helsinki...... researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict...

  6. The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects.

    Science.gov (United States)

    Tanno, Luciana Kase; Kerr, Daniel Shikanai; dos Santos, Bernardo; Talib, Leda Leme; Yamaguti, Célia; Rodrigues, Helcio; Gattaz, Wagner Farid; Kalil, Jorge

    2015-01-01

    Although aromatic anticonvulsants are usually well tolerated, they can cause cutaneous adverse drug reactions in up to 10% of patients. The clinical manifestations of the antiepileptics-induced hypersensitivity reactions (AHR) vary from mild skin rashes to severe cutaneous drug adverse reactions which are related to high mortality and significant morbidity. Genetic polymorphisms in cytochrome P450 genes are associated with altered enzymatic activity and may contribute to the risk of AHR. Here we present a case-control study in which we genotyped SNPs of CYP2C19, 2C9 and 3A5 of 55 individuals with varying severities of AHR, 83 tolerant, and 366 healthy control subjects from São Paulo, Brazil. Clinical characterization was based on standardized scoring systems and drug patch test. All in vivo investigation followed the ENDA (European Network of Drug Allergy) recommendations. Genotype was determined by real time PCR using peripheral blood DNA as a template. Of all 504 subjects, 65% were females, 45% self-identified as Afro-American, 38% as Caucasian and 17% as having non-African mixed ascendancy. Amongst 55 subjects with AHR, 44 had severe cutaneous drug adverse reactions. Of the 46 drug patch tests performed, 29 (63%) were positive. We found a strong association between the absence of CYP3A5*3 and tolerant subjects when compared to AHR (p = 0.0002, OR = 5.28 [CI95% 2.09-14.84]). None of our groups presented positive association with CYP2C19 and 2C9 polymorphisms, however, both SNPs contributed to separation of cases and tolerants in a Classification and Regression Tree. Our findings indicate that drug metabolism genes can contribute in the tolerability of antiepileptics. CYP3A5*3 is the most prevalent CYP3A5 allele associated with reduced enzymatic function. The current study provides evidence that normal CYP3A5 activity might be a protective factor to aromatic antiepileptics-induced hypersensitivity reactions in Brazilian subjects.

  7. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

    Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

  8. To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

    Science.gov (United States)

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-23

    Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic

  9. The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity.

    Science.gov (United States)

    Morén, Constanza; Juárez-Flores, Diana Luz; Cardellach, Francesc; Garrabou, Glòria

    2016-01-01

    Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. One hundred and forty-five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage.

  10. Hiponatremia in the practice of a psychiatrist. Part 1: SIADH syndrome and drug-induced hyponatremia.

    Directory of Open Access Journals (Sweden)

    Stelmach Ewa

    2017-06-01

    Full Text Available Introduction. Hyponatremia is an important part of psychiatric practice. In order to analyze its causes and symptoms, the literature on hyponatremia in psychiatric patients has been reviewed. The work has been divided into two separate manuscripts. In the first one the authors discuss the syndrome of inappropriate antidiuretic hormone secretion (SIADH and hyponatremia occurring with the use of psychotropic drugs (antidepressants, antipsychotics, normotimics, while the second paper discusses research on psychogenic polydipsia. The causes of hyponatremia in patients treated in psychiatric wards include: water intoxication associated with polydipsia, somatic comorbidities, side effect of internal medicine and psychiatric drugs. The most common mechanism leading in these cases to hyponatremia is the syndrome of inappropriate secretion of vasopressin (SIADH. The SIADH syndrome is a group of symptoms, first described in 1967 by Schwartz and Bartter in The American Journal of Medicine, which results from the hypersecretion of antidiuretic hormone, also called vasopressin, which causes patients to develop normovolemic hyponatremia. The phenomenon of drug-induced hyponatremia in psychiatric practice is generally observed with the use of antidepressants, antipsychotics and anti-epileptic drugs (used in psychiatry as normotimic drugs.

  11. Specific safety and tolerability considerations in the use of anticonvulsant medications in children

    Directory of Open Access Journals (Sweden)

    Crepeau A

    2012-06-01

    Full Text Available Amy Z Crepeau,1 Brian D Moseley,2 Elaine C Wirrell31Division of Epilepsy, Department of Neurology, Mayo Clinic, 2Department of Neurology, Mayo Clinic, 3Divisions of Epilepsy and Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USAAbstract: Epilepsy is one of the most common neurological disorders in the pediatric age range, and the majority of affected children can be safely and effectively treated with antiepileptic medication. While there are many antiepileptic agents on the market, specific drugs may be more efficacious for certain seizure types or electroclinical syndromes. Furthermore, certain adverse effects are more common with specific classes of medication. Additionally patient-specific factors, such as age, race, other medical conditions, or concurrent medication use may result in higher rates of side effects or altered efficacy. Significant developmental changes in gastric absorption, protein binding, hepatic metabolism, and renal clearance are seen over the pediatric age range, which impact pharmacokinetics. Such changes must be considered to determine optimal dosing and dosing intervals for children at specific ages. Furthermore, approximately one third of children require polytherapy for seizure control, and many more take concurrent medications for other conditions. In such children, drug–drug interactions must be considered to minimize adverse effects and improve efficacy. This review will address issues of antiepileptic drug efficacy, tolerability and ease of use, pharmacokinetics, and drug–drug interactions in the pediatric age range.Keywords: antiepileptic drugs, drug–drug interactions, pharmacokinetics

  12. Anti-Epileptic Drugs Delay Age-Related Loss of Spiral Ganglion Neurons via T-type Calcium Channel

    Science.gov (United States)

    Lei, Debin; Gao, Xia; Perez, Philip; Ohlemiller, Kevin K; Chen, Chien-Chang; Campbell, Kevin P.; Hood, Aizhen Yang; Bao, Jianxin

    2011-01-01

    Loss of spiral ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Cav3.1, Cav3.2, and Cav3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of spiral ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Cav3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve spiral ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of spiral ganglion neurons. PMID:21640179

  13. 78 FR 42084 - Electronic Study Data Submission; Data Standard Support; Availability of the Center for Drug...

    Science.gov (United States)

    2013-07-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0812... so that safe and effective products can get to market sooner. It is aligned with the objectives of... as captured in the FDA Safety and Innovation Act. The CDER Data Standards Strategy supersedes version...

  14. [Changes in prescription patterns for peripheral and cerebral vasoactive drugs before and after establishing prescription standards in France].

    Science.gov (United States)

    Vuittenez, F; Guignard, E; Comte, S

    1999-01-23

    Assess changes in the number of prescriptions for peripheral and cerebral vasoactive drugs for the treatment of lower limb arteritis and cerebrovascular disease since the promulgation in 1995 of prescription standards for the treatment of lower limb arteritis. Assess compliance to prescription standards with a detailed analysis of patient features, prescriptions written for lower limb arteritis, cerebrovascular disease and concomitant diseases and evaluate changes in treatment costs for lower limb arteritis and cerebrovascular disease as well as cost of the full prescription, including treatments for associated diseases. This study was based on data recorded during the Permanent Study of Medical Prescriptions conducted from March 1994 to February 1995 and from March 1995 to February 1996 by the IMS. Prescription costs were established from the National Description Files of the IMS. Treatment costs were expressed as public price (FF) tax included. Prescriptions meeting the following criteria were selected for each period: prescriptions written by general practitioners for drugs with peripheral and cerebral vasoactivity (excepting calcium antagonists with a cerebral target) belonging to the Anatomic Therapeutic Classes C4A1 of the European Pharmaceutical Marketing Research Association, Bromly 1996; prescriptions for diagnoses 447.6 (arteritis) and 437.9 (cerebrovascular disease) according to the 9th WHO classification. A random sample of 500 prescriptions was selected to calculate costs. Since the advent of the prescription standards in 1995, prescriptions have dropped off by 6.3% for lower limb arteritis and by 14.8% for cerebrovascular disease. There was a 3.7 point decline in the percentage of multiple prescriptions of vasoactive drugs for lower limb arteritis (21.7% prior to March 1995 versus 18% after promulgation of the prescription standards, p > 0.1) and a 1.8 increase in the percentage of multiple prescriptions for cerebrovascular disease (14% prior to March

  15. Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Pierangelo eCifelli

    2013-07-01

    Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.

  16. Perspectives of drug treatment of obesity

    Directory of Open Access Journals (Sweden)

    Alfredo Halpern

    2006-03-01

    Full Text Available The perspectives in the pharmacological treatment of obesitycan be classified in two classes: drugs already in the market,in advanced clinical trial or in final approval, or drugs in earlydevelopment. Among the first class are antiepileptic drugslike topiramate (although it was studied for obesity treatmentit was descontinued for this indication because of the highdrop-out rate in clinical trials and zonisamide (with someshort term studies in obese adults; antidepressives likebupropion (that leads to weight reduction and also diminishesthe weight gain associated to smoking cessation andradafaxine (a bupropion metabolite, without reported trials inobese subjects; glucagon-like peptide-1 analogues like exenatide(exendin-4, pramlintide and liraglutide (with studiesin type 2 diabetic obese subjects and the selective blockerof the cannabinoid-1 receptor, rimonabant, with a large bodyof studies (Rimonabant in Obesity, RIO-Europe, RIO-NorthAmerica, RIO-Lipids and RIO-Diabetes, involving more than6.600 patients with obesity, with and without diabetes, beingan important perspective of treatment for obesity andmetabolic syndrome. In early phase of development, we canreport some energy balance modulators like neuropeptide Yantagonists, melanocortin agonists, leptine and its analoguesand ciliary neurotrophic factor (axokine; termogenic agentslike agonists of the beta-3 adrenergic receptor, uncouplingagents of the mithocondrial membrane and peripheralmodulators of the energy balance (cholecystokinine.

  17. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet

    Science.gov (United States)

    Rogawski, Michael A.; Löscher, Wolfgang; Rho, Jong M.

    2016-01-01

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. PMID:26801895

  18. Molecular Genetics of Drug-resistance in Epilepsies

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    Kurupath Radhakrishnan

    2015-06-01

    Full Text Available Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs, etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs, etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic

  19. In vitro comparison of the activity of various antibiotics and drugs against new Taiwan isolates and standard strains of avian mycoplasma.

    Science.gov (United States)

    Lin, M Y

    1987-01-01

    Twenty-nine antibiotics or drugs were incorporated individually into mycoplasma agar to evaluate their inhibitory activity against avian mycoplasmas: 100 recent Taiwan isolates of 7 serotypes and 10 standard strains of 7 serotypes were tested. All of the standard strains were very sensitive to erythromycin, chlorotetracycline, doxycycline, minocycline, and tetracycline, but the local isolates were highly resistant to these antibiotics. The drugs or antibiotics that possessed an MIC90 of 50 micrograms/ml or less against the local isolates were tiamulin (less than 0.4 micrograms/ml), lincospectin (2.7), josamycin (2.7), lincomycin (3.0), spectinomycin (4.8), tylosin (6.0), kanamycin (6.0), chloramphenicol (6.0), gentamicin (7.5), apramycin (24.5), doxycycline (27.4), minocycline (29.0), spiramycin (30.0), colistin (44.3), leucomycin (45.0), and streptomycin (50.0). The MIC90 of the other antibiotics or drugs was greater than 50 micrograms/ml. None of the isolates or strains were sensitive to nalidixic acid, ronidazole, penicillin, ampicillin, cephalexin, carbadox, or four sulfa drugs at a concentration about 5 times the therapeutic level.

  20. Does mechanism of drug action matter to inform rational polytherapy in epilepsy?

    Science.gov (United States)

    Giussani, Giorgia; Beghi, Ettore

    2013-05-01

    When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.

  1. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures.

    Science.gov (United States)

    Chrościńska-Krawczyk, Magdalena; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanisław J

    2009-01-01

    Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. Using the mouse maximal electroshock model, the present study was undertaken so as to ascertain whether caffeine affects the anticonvulsant efficacy of the new antiepileptic drugs lamotrigine, oxcarbazepine and tiagabine. The results indicate that neither acute nor chronic caffeine administration (up to 46.2 mg/kg) affected the ED(50) values of oxcarbazepine or lamotrigine against maximal electroshock. Similarly, caffeine did not modify the tiagabine electroconvulsive threshold. Furthermore, caffeine had no effect on oxcarbazepine, lamotrigine and tiagabine associated adverse effects such as impairment of motor coordination (measured by the chimney test) or long-term memory (measured by the passive avoidance task). Concurrent plasma concentration measurements revealed no significant effect on lamotrigine and oxcarbazepine concentrations. For tiagabine, however, chronic caffeine (4 mg/kg) administration was associated with an increase in tiagabine concentrations. In conclusion, caffeine did not impair the anticonvulsant effects of lamotrigine, oxcarbazepine, or tiagabine as assessed by electroconvulsions in mice. Also, caffeine was without effect upon the adverse potential of the studied antiepileptic drugs. Thus caffeine may not necessarily adversely affect the efficacy of all antiepileptic drugs and this is an important observation.

  2. A review on the status of quality control and standardization of herbal drugs in India

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    Anju Dhiman

    2016-01-01

    Full Text Available Background: Most of the herbal medicines in the world originate from the developing countries. There are ample opportunities for these countries to expand their global export. The world market for botanical medicines including drug products and raw materials has been estimated to have an annual growth rate between 5% and 15%. Total global botanical drug market is estimated at US$62 billion and is expected to grow to the tune of US$5 trillion by the year 2050. In the USA alone, the usage of botanicals has been increased by 380% between the years 1990 and 1997. Materials and Methods: Ayurveda, the Indian system of medicine, is one of the ancient, yet living traditions that face a typical Western bias. Widespread and growing use of botanicals has created public health challenges globally in terms of quality, safety, and efficacy. Results and Discussion: The development of parameters for standardization and quality control of botanicals is a challenging task. Various regulatory authorities, research organizations, and botanical drug manufacturers have contributed in developing guiding principles and addressing issues related to the quality, safety, and efficacy. Conclusions: The present review describes the regulatory aspects of herbal drugs in India and various other countries.

  3. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.

    Science.gov (United States)

    Seppala, Lotta J; van de Glind, Esther M M; Daams, Joost G; Ploegmakers, Kimberley J; de Vries, Max; Wermelink, Anne M A T; van der Velde, Nathalie

    2018-04-01

    The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication

  4. Risk assessment of antiepileptic drugs in pregnancy

    NARCIS (Netherlands)

    Boersma-Jentink, Janneke

    2011-01-01

    Vrouwen die anti-epileptica nodig hebben en zwanger willen worden moeten ruim voor de conceptie de neuroloog consulteren en hun kinderwens kenbaar maken, zodat de medicatie, het handhaven of veranderen van de therapie, hierop afgestemd kan worden. Want uiteindelijk kan de beste therapie alleen

  5. On the slow diffusion of Point of Care systems in Therapeutic Drug Monitoring

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    Barbara eSanavio

    2015-02-01

    Full Text Available Recent advancements in point-of-care technologies show great transformative promises for personalized preventative and predictive medicine. However, fields like therapeutic drug monitoring, that first allowed for personalized treatment of patient’ disease, still lag behind in the widespread application of point-of-care devices for monitoring of patients. Surprisingly, very few applications in commonly monitored drugs, such as anti-epileptics, are paving the way for a point of care (PoC approach to patient’ therapy monitoring, compared to other fields –like intensive care cardiac markers monitoring, glycemic controls in diabetes, or bench-top hematological parameters analysis at the local drug store. Such delay in the development of portable fast clinically effective drug monitoring devices is in our opinion due more to an inertial drag on the pervasiveness of these new devices into the clinical field than a lack of technical capability. At the same time, some very promising technologies failed in the clinical practice for inadequate understanding of the outcome parameters necessary for a relevant technological breakthrough that has superior clinical performance. We hope, by overviewing both therapeutic drug monitoring practice and its yet unmet needs and latest advancement in micro and nanotechnology applications to PoC clinical devices, to help bridging the two communities, the one exploiting analytical technologies and the one mastering the most advanced techniques, into translating existing and forthcoming technologies in effective devices.

  6. Brivaracetam: a rational drug discovery success story

    Science.gov (United States)

    Rogawski, M A

    2008-01-01

    Levetiracetam, the α-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a ∼90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity in animal seizure models. Recent phase II clinical trials demonstrating that brivaracetam is efficacious and well tolerated in the treatment of partial onset seizures have validated the strategy of the discovery programme. Brivaracetam is among the first clinically effective AEDs to be discovered by optimization of pharmacodynamic activity at a molecular target. PMID:18552880

  7. Anesthetic drugs in status epilepticus: Risk or rescue?

    Science.gov (United States)

    Marsch, Stephan; Fuhr, Peter; Kaplan, Peter W.; Rüegg, Stephan

    2014-01-01

    Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs. PMID:24319039

  8. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

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    Dini Gabriele

    2004-10-01

    Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

  9. Drug: D00709 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0709.gif ... Neuropsychiatric agent ... DG02038 ... Piracetam antiepileptics Same as: C07841 Therapeutic category: ...1139 ATC code: N03AX14 Chemical group: DG02505 ... Piracetam derivative SV2A [HSA:9900] [KO:K06258] ... CAS: 102

  10. Drug abuse: newly-emerging drugs and trends.

    Science.gov (United States)

    Davis, Gregory G

    2012-09-01

    Drug abusers have access to new, more potent compounds that evade existing laws by virtue of their novel chemical structures. These drugs are available for purchase at stores and over the internet. The drugs are not illegal because they are so new that laws have not yet been passed to ban them. These drugs are leading to emergency department visits for cardiovascular, neurologic, and psychiatric complications. Standard drug screens are not designed to detect these new substances. The internet provides access to drugs for substance abusers but also provides physicians speed of access to the habits of substance abusers.

  11. Spanish Compliance With Guidelines for Prescribing Four Drugs in the Intensive Phase of Standard Tuberculosis Treatment.

    Science.gov (United States)

    García-García, José-María; Rodrigo, Teresa; Casals, Martí; Ruiz-Manzano, Juan; Pascual-Pascual, Teresa; Caylà, Joan A

    2016-05-01

    International and Spanish guidelines recommend a 4-drug regimen in the intensive treatment of tuberculosis (TB). The aim of our study was to determine if these recommendations are followed in Spain, and the factors associated with the use of 3 drugs (standard regimen without ethambutol). Observational, multicenter, retrospective analysis of data from patients diagnosed with TB in practically all Spanish Autonomous Communities between 2007 and 2102. Factors associated with the use of 3 drugs were analyzed using logistic regression, and odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. A total of 3,189 patients were included, 1,413 (44.3%) of whom received 3 drugs. The percentage of 3-drug users among patients with positive sputum smear was 41.2%; among patients with resistance to at least 1 drug, 36.1%; among HIV-infected patients, 31.4%; and among immigrants, 24.8%. Factors associated with the use of 3 drugs were: female sex (OR=1.18; CI: 1.00-1.39); native Spanish (OR=3.09; CI: 2.58-3.70); retired (OR=1.42; CI: 1.14-1.77); homeless (OR=3.10; CI: 1.52-6.43); living alone (OR=1.62; CI: 1.11-2.36); living in a family (OR=1.97; CI: 1.48-2.65); seen by specialists in the region (OR=1.37; CI: 1.10;1.70); no HIV infection (OR=1.63; CI: 1.09-2.48); and negative sputum smear with positive culture (OR=1.59; CI: 1.25-2.02). A large proportion of TB patients receive intensive treatment with 3 drugs. TB treatment recommendations should be followed, both in routine clinical practice and by the National Plan for Prevention and Control of Tuberculosis in Spain. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

  12. [Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

    Science.gov (United States)

    Jóźwiak, Sergiusz

    2007-01-01

    Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy.

  13. What is the standard approach to assessment of an unprovoked seizure in an adult?: HONG KONG.

    Science.gov (United States)

    Kwan, Patrick

    2012-12-01

    Since Hong Kong is highly urbanized and acute public hospitals have been established across the city, most patients with unprovoked seizures not already receiving antiepileptic drug (AED) therapy, particularly convulsive seizures, will be admitted as emergency for assessment. A thorough history is taken from the patient and any witnesses to the seizure. This includes the circumstance of the seizures, detailed symptoms and signs experienced by the patient and witnessed by others before, during, and after the seizure, any potential precipitating factors, history of previous seizures (that the patient might have overlooked), and history of previous brain insults that might have increased the risk of epilepsy later in life, including gestational and birth history, history of childhood febrile seizure, significant head trauma, any family history of epilepsy or seizures, comorbidities, current medications, drug and alcohol abuse, and social history including employment, driving, and living circumstances. A detailed physical and neurologic examination is performed.

  14. Determinação simultânea de topiramato, carbamazepina, fenitoína e fenobarbital em plasma empregando cromatografia a gás com detector de nitrogênio e fósforo

    Directory of Open Access Journals (Sweden)

    Roberta Zilles Hahn

    2013-01-01

    Full Text Available Topiramate and the other frequently co-administered antiepileptic drugs carbamazepine, phenytoin and phenobarbital were determined in 100 µL plasma samples by gas chromatography with nitrogen phosphorus detection (GC-NPD, after a one-step liquid-liquid extraction with ethyl acetate, followed by flash methylation with trimethylphenylammonium hydroxide. Total chromatographic run time was 12.5 min. Intra-assay and inter-assay precision was 2.5-7.3% and 1.6-5.2%, respectively. Accuracy was 100.1-104.2%. The limit of quantitation was 1 µg mL-1 for all analytes, proving suitable for routine application in therapeutic drug monitoring of antiepileptic drugs.

  15. [Psychoactive drugs and costs in the Madrid III (Valdemoro) prison].

    Science.gov (United States)

    Algora-Donoso, I; Varela-González, O

    2008-01-01

    Annual pharmaceutical expenditures in prisons increases dramatically and the rising costs of psychoactive drugs have especially contributed to this. These drugs are often prescribed in order to find therapeutic uses in the field of personality disorders, addictions, and dysfunctional behaviours that are not included in the authorized indications (compassionate use). This study has enabled a detailed description of the use of psychoactive drugs at the Madrid III prison, a centre with one of the lowest levels of pharmaceutical expenditure in this autonomous community. During a two-week period, all prescriptions of psychoactive drugs were collected and registered along with data of several possible conditioning factors. 20.5% of the population was receiving some kind of psychoactive drug; 76% of those inmates undergoing treatment were receiving one or two substances; 65% were taking anxiolytics, 38% antidepressants and 27% antipsychotics. The total amount of psychoactive drugs consumed was 9,840 defined daily doses, 46% of which were anxiolytics, 17% antidepressants and 14% antipsychotics. The total cost of the fortnight's treatment was euros 5,379 with a saving of euro 611 due to requesting and selecting offers carried out by the pharmacist. 72% of the costs were spent on anti-psychotics and the newer psychoactive drugs, representing 66% of the prescriptions, accounted for 98% of expenditure. The prescriber was one of the key influential factors over the amount, type and cost of the treatments. There are signs that compassionate use of current antipsychotics and antiepileptics, and newer antidepressants are a main cause of the dramatic increase in the costs, with cost-efficiency not always clearly demonstrated. These results are not an isolated fact restricted only to prisons, as demonstrated by consumption data published by the National Health System in the same year.

  16. Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?

    Science.gov (United States)

    Romo, Matthew L; Carpio, Arturo; Kelvin, Elizabeth A

    2014-04-01

    Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co-administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized. © 2014, The American College of Clinical Pharmacology.

  17. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Science.gov (United States)

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  18. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years.

    Science.gov (United States)

    Yasiry, Zeid; Shorvon, Simon D

    2012-12-01

    Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100-year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug's current clinical utilization. The introduction of controlled drug regulations, the comparative cost of phenobarbital, and its inclusion on the World Health Organization (WHO) essential drug list are discussed. It is one of the few drugs on the formulary in 1912 that is still listed today, and remarkably its efficacy in epilepsy has not been significantly bettered. The current recommendation by the WHO is that phenobarbital should be offered as the first option for therapy for convulsive epilepsy in adults and children if availability can be ensured. This is rated as a strong recommendation because of the proven efficacy and low cost of phenobarbital, and despite its perceived side-effect profile and the practical problems of access. Whether this recommendation puts "a hierarchy on the brain," as has been suggested, is arguable. Much still needs to be learned about the drug's effects, and the issues raised by phenobarbital have lessons for all antiepileptic drug therapy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  19. A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

    Science.gov (United States)

    Mirone, V; Sorrentino, R; di Villa Bianca, R; Imbimbo, C; Palmieri, A; Fusco, F; Tajana, G; Cirino, G

    2000-01-01

    The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

  20. Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal® vet, Phenoleptil®) in dogs

    Science.gov (United States)

    2013-01-01

    Background In human medicine, adverse outcomes associated with switching between bioequivalent brand name and generic antiepileptic drug products is a subject of concern among clinicians. In veterinary medicine, epilepsy in dogs is usually treated with phenobarbital, either with the standard brand name formulation Luminal® or the veterinary products Luminal® vet and the generic formulation Phenoleptil®. Luminal® and Luminal® vet are identical 100 mg tablet formulations, while Phenoleptil® is available in the form of 12.5 and 50 mg tablets. Following approval of Phenoleptil® for treatment of canine epilepsy, it was repeatedly reported by clinicians and dog owners that switching from Luminal® (human tablets) to Phenoleptil® in epileptic dogs, which were controlled by treatment with Luminal®, induced recurrence of seizures. In the present study, we compared bioavailability of phenobarbital after single dose administration of Luminal® vet vs. Phenoleptil® with a crossover design in 8 healthy Beagle dogs. Both drugs were administered at a dose of 100 mg/dog, resulting in 8 mg/kg phenobarbital on average. Results Peak plasma concentrations (Cmax) following Luminal® vet vs. Phenoleptil® were about the same in most dogs (10.9 ± 0.92 vs. 10.5 ± 0.77 μg/ml), and only one dog showed noticeable lower concentrations after Phenoleptil® vs. Luminal® vet. Elimination half-life was about 50 h (50.3 ± 3.1 vs. 52.9 ± 2.8 h) without differences between the formulations. The relative bioavailability of the two products (Phenoleptil® vs. Luminal® vet.) was 0.98 ± 0.031, indicating that both formulations resulted in about the same bioavailability. Conclusions Overall, the two formulations did not differ significantly with respect to pharmacokinetic parameters when mean group parameters were compared. Thus, the reasons for the anecdotal reports, if true, that switching from the brand to the generic formulation of phenobarbital may lead to

  1. Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal(®) vet, Phenoleptil(®)) in dogs.

    Science.gov (United States)

    Bankstahl, Marion; Bankstahl, Jens P; Löscher, Wolfgang

    2013-10-09

    In human medicine, adverse outcomes associated with switching between bioequivalent brand name and generic antiepileptic drug products is a subject of concern among clinicians. In veterinary medicine, epilepsy in dogs is usually treated with phenobarbital, either with the standard brand name formulation Luminal(®) or the veterinary products Luminal(®) vet and the generic formulation Phenoleptil(®). Luminal(®) and Luminal(®) vet are identical 100 mg tablet formulations, while Phenoleptil(®) is available in the form of 12.5 and 50 mg tablets. Following approval of Phenoleptil(®) for treatment of canine epilepsy, it was repeatedly reported by clinicians and dog owners that switching from Luminal(®) (human tablets) to Phenoleptil(®) in epileptic dogs, which were controlled by treatment with Luminal(®), induced recurrence of seizures. In the present study, we compared bioavailability of phenobarbital after single dose administration of Luminal(®) vet vs. Phenoleptil(®) with a crossover design in 8 healthy Beagle dogs. Both drugs were administered at a dose of 100 mg/dog, resulting in 8 mg/kg phenobarbital on average. Peak plasma concentrations (Cmax) following Luminal(®) vet vs. Phenoleptil(®) were about the same in most dogs (10.9 ± 0.92 vs. 10.5 ± 0.77 μg/ml), and only one dog showed noticeable lower concentrations after Phenoleptil(®) vs. Luminal(®) vet. Elimination half-life was about 50 h (50.3 ± 3.1 vs. 52.9 ± 2.8 h) without differences between the formulations. The relative bioavailability of the two products (Phenoleptil(®) vs. Luminal(®) vet.) was 0.98 ± 0.031, indicating that both formulations resulted in about the same bioavailability. Overall, the two formulations did not differ significantly with respect to pharmacokinetic parameters when mean group parameters were compared. Thus, the reasons for the anecdotal reports, if true, that switching from the brand to the generic formulation of phenobarbital may lead to recurrence of

  2. 21 CFR 130.9 - Sulfites in standardized food.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Sulfites in standardized food. 130.9 Section 130.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD STANDARDS: GENERAL General Provisions § 130.9 Sulfites in standardized food...

  3. Tics and other stereotyped movements as side effects of pharmacological treatment.

    Science.gov (United States)

    Madruga-Garrido, Marcos; Mir, Pablo

    2013-01-01

    Tics and other stereotyped abnormal movements can be seen as adverse effects of some pharmacologic drugs. Among these drugs, antipsychotics may provoke tardive syndromes after a chronic exposure, primarily in the case of typical antipsychotics. These syndromes include tardive tics, tardive dyskinesia, or tardive akathisia, which present with tics or stereotyped movements as a clinical phenomenon. Psychostimulants (mainly methylphenidate) have traditionally been associated with the appearance of tics due to the increased dopamine activity caused by stimulants. Nevertheless, in recent years, several studies have concluded not only that methylphenidate does not exacerbate or reactivate tics but also that tics can improve with its use in patients with associated attention deficit and hyperactivity disorder and tic disorder. Antiepileptic drugs, although infrequently, can also induce tics, with carbamazepine and lamotrigine described as tic inducers. Other antiepileptics, including levetiracetam and topiramate, have been proposed as a potential treatment for tic disorders due to a positive effect on tics, especially in those with associated epileptic disorder. Clinical and therapeutic approaches to tics and stereotyped movements after exposure to antipsychotics, stimulants, and antiepileptic drugs will be reviewed in this chapter. © 2013 Elsevier Inc. All rights reserved.

  4. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine

    Directory of Open Access Journals (Sweden)

    Catherine E. Creeley

    2013-07-01

    Full Text Available Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and several drugs, including alcohol, that are abused by pregnant women, trigger widespread neuroapoptosis in the developing brain of several animal species, including non-human primates. Caffeine (CAF is often administered to premature infants to stimulate respiration, and these infants are also exposed simultaneously to anesthetic drugs for procedural sedation and/or surgical procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may heavily consume CAF. We administered CAF to infant mice alone or in combination with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which are drugs of abuse and/or drugs frequently used in pediatric medicine, and found that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the neuroapoptogenic action of each of these other drugs. Exposure of infant mice to CAF + phencyclidine resulted in long-term impairment in behavioral domains relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF + diazepam resulted in long-term learning/memory impairment. At doses used in these experiments, these behavioral impairments either did not occur or were substantially less pronounced in mice exposed to CAF alone or to phencyclidine or diazepam alone. CAF currently enjoys the reputation of being highly beneficial and safe for use in neonatal medicine. Our data suggest the need to consider whether CAF may have harmful as well as beneficial effects on the developing brain, and the need for research aimed at understanding the full advantage of its beneficial effects while avoiding its potentially harmful effects.

  5. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs.

  6. Zonisamide in the management of epilepsy in the elderly

    Directory of Open Access Journals (Sweden)

    Romigi A

    2015-06-01

    Full Text Available Andrea Romigi,1,2 Eti A Femia,3 Cinzia Fattore,4 Giuseppe Vitrani,1 Giancarlo Di Gennaro,1 Valentina Franco4 1Istituto Neurologico Mediterraneo, IRCCS Neuromed, Pozzilli (IS, Italy; 2Neurophysiopathology Department, University of Rome Tor Vergata, Rome, Italy; 3Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy; 4Clinical Trial Centre & Antiepileptic Drugs, C. Mondino National Neurological Institute, Pavia, Italy Abstract: Zonisamide (ZNS, a second-generation antiepileptic drug, indicated as add-on treatment of focal epilepsy, has been recently approved as monotherapy for the treatment of partial seizures in adults affected by newly diagnosed epilepsy in Europe. Evidence on the efficacy and tolerability of antiepileptic drugs in the elderly is still lacking as these patients are frequently excluded from clinical trials. Here, a comprehensive overview of available data regarding the use of ZNS in the treatment of epilepsy in elderly people is provided. In a pooled analysis conducted in patients aged ≥65 years, no new/unexpected safety findings have emerged. Few data from uncontrolled investigations suggest that ZNS may be effective and well tolerated when administered as monotherapy or adjunctive antiepileptic treatment in the elderly. However, evidence from these observational studies is less than satisfactory, and randomized controlled trials focused on these patients are still needed. Keywords: zonisamide, elderly, epilepsy, safety, efficacy

  7. Perampanel in the management of partial-onset seizures: a review of safety, efficacy, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Schulze-Bonhage A

    2015-08-01

    Full Text Available Andreas Schulze-Bonhage, Mandy Hintz Epilepsy Center, University Medical Center Freiburg, Freiburg, Germany Abstract: Perampanel (PER is a novel antiepileptic drug recently introduced for the adjunctive treatment in epilepsy patients aged 12 years or older with partial-onset seizures with or without secondary generalization in the US and Europe. Its antiepileptic action is based on noncompetitive inhibition of postsynaptic AMPA receptors, decreasing excitatory synaptic transmission. Evaluation of efficacy in three placebo-controlled randomized Phase III studies showed that add-on therapy of PER decreased seizure frequencies significantly compared to placebo at daily doses between 4 mg/day and 12 mg/day. PER’s long half-life of 105 hours allows for once-daily dosing that is favorable for patient compliance with intake. Long-term extension studies showed a 62.5%–69.6% adherence of patients after 1 year of treatment, comparing favorably with other second-generation antiepileptic drugs. Whereas these trials demonstrated an overall favorable tolerability profile of PER, nonspecific central nervous system adverse effects like somnolence, dizziness, headache, and fatigue may occur. In addition, neuropsychiatric disturbances ranging from irritability to suicidality were reported in several case reports; both placebo-controlled and prospective long-term extension trials showed a low incidence of such behavioral and psychiatric complaints. For early recognition of neuropsychiatric symptoms like depression, anxiety, and aggression, slow titration and close monitoring during drug introduction are mandatory. This allows on the one hand to recognize patients particularly susceptible to adverse effects of the drug, and on the other hand to render the drug’s full potential of seizure control available for the vast majority of patient groups tolerating the drug well. Keywords: epilepsy, antiepileptic drugs, AMPA receptor, structural epilepsy, partial

  8. Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

    Science.gov (United States)

    Zaccara, G; Giorgi, F S; Amantini, A; Giannasi, G; Campostrini, R; Giovannelli, F; Paganini, M; Nazerian, P

    2018-06-01

    Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  10. Successful Treatment of a Drug-Resistant Epilepsy by Long-term Transcranial Direct Current Stimulation: A Case Report.

    Science.gov (United States)

    San-Juan, Daniel; Sarmiento, Carlos Ignacio; González, Katia Márquez; Orenday Barraza, José Manuel

    2018-01-01

    Transcranial direct current stimulation (tDCS) is a reemerged noninvasive cerebral therapy used to treat patients with epilepsy, including focal cortical dysplasia, with controversial results. We present a case of a 28-year-old female with left frontal cortical dysplasia refractory to antiepileptic drugs, characterized by 10-15 daily right tonic hemi-body seizures. The patient received a total of seven sessions of cathodal tDCS (2 mA, 30 min). The first three sessions were applied over three consecutive days, and the remaining four sessions of tDCS were given each at 2-week intervals. At the 1-year follow-up, the patient reported to have a single seizure per month and only mild adverse events.

  11. Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

    Science.gov (United States)

    Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

    2009-01-01

    In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

  12. Prescription drug use during pregnancy in France: a study from the national health insurance permanent sample.

    Science.gov (United States)

    Demailly, Romain; Escolano, Sylvie; Quantin, Catherine; Tubert-Bitter, Pascale; Ahmed, Ismaïl

    2017-09-01

    To provide an up-to-date account of drug prescription during pregnancy in France from 2011 to 2014 using the permanent sample of the French national computerized healthcare database and with a focus on recommended supplementations, fetotoxic drugs and teratogenic drugs. All pregnancies identified by the International Classification of Diseases, 10th Revision codes list in the hospitalization database, lasting more than 9 weeks of amenorrhea and whose delivery occurred between 01/01/2011 and 12/31/2014, were included. Drugs delivered between the trimester before and until the end of the pregnancy were included. Drug exposure prevalence was calculated for each year and according to pregnancy trimesters. The study included 28,491 pregnancies with a median number of 9 [5-13] (median [IQ range]) drugs delivered. The most prescribed drug class was antianemia (in 72.5% of exposed). The prescription rate of recommended vitamins (B9 and D) increased over the study period (+10%). Influenza vaccination also increased but remained at a low rate (1%). Exposure to fetotoxic drugs decreased as pregnancy advanced. Exposure to the main teratogenic antiepileptics was stable over the study period. Low-income pregnant women had a higher average drug consumption except for recommended vitamins. Pregnant French women are among the largest consumers of prescription medications worldwide. Overall, the dispensation trends observed in this study are in line with the recommendations of the French National College of Gynecologists and Obstetricians. Nevertheless, while being low, exposure to fetotoxic drugs, teratogenic drugs or those under safety alerts still occurred. Supplementations and vaccines in low-income pregnant women should also be increased. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Pharmacogenomics and epilepsy: the road ahead.

    LENUS (Irish Health Repository)

    Cavalleri, Gianpiero L

    2011-10-01

    Epilepsy is one of the most common, serious neurological disorders, affecting an estimated 50 million people worldwide. The condition is typically treated using antiepileptic drugs of which there are 16 in widespread use. However, there are many different syndrome and seizure types within epilepsy and information guiding clinicians on the most effective drug and dose for individual patients is lacking. Further, all of the antiepileptic drugs have associated adverse reactions, some of which are severe and life-threatening. Here, we review the pharmacogenomic work to date in the context of these issues and comment on key aspects of study design that are required to speed up the identification of clinically relevant genetic factors.

  14. Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

    International Nuclear Information System (INIS)

    Weissman, Ben Avi; Raveh, Lily

    2008-01-01

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission

  15. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.

    Science.gov (United States)

    Atkin, Talia A; Maher, Chani M; Gerlach, Aaron C; Gay, Bryant C; Antonio, Brett M; Santos, Sonia C; Padilla, Karen M; Rader, JulieAnn; Krafte, Douglas S; Fox, Matthew A; Stewart, Gregory R; Petrovski, Slavé; Devinsky, Orrin; Might, Matthew; Petrou, Steven; Goldstein, David B

    2018-04-01

    Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. We developed cellular models expressing wild-type or an R1872Q mutation in the Na v 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  16. Estimation of the standardized risk difference and ratio in a competing risks framework: application to injection drug use and progression to AIDS after initiation of antiretroviral therapy.

    Science.gov (United States)

    Cole, Stephen R; Lau, Bryan; Eron, Joseph J; Brookhart, M Alan; Kitahata, Mari M; Martin, Jeffrey N; Mathews, William C; Mugavero, Michael J

    2015-02-15

    There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

    Science.gov (United States)

    Ting, Tricia Y; Jiang, Wenlei; Lionberger, Robert; Wong, Jessica; Jones, Jace W; Kane, Maureen A; Krumholz, Allan; Temple, Robert; Polli, James E

    2015-09-01

    To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs

  18. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    Science.gov (United States)

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

  19. Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition to Support Model-Informed Drug Discovery and Development.

    Science.gov (United States)

    Wilkins, J J; Chan, Pls; Chard, J; Smith, G; Smith, M K; Beer, M; Dunn, A; Flandorfer, C; Franklin, C; Gomeni, R; Harnisch, L; Kaye, R; Moodie, S; Sardu, M L; Wang, E; Watson, E; Wolstencroft, K; Cheung, Sya

    2017-05-01

    Pharmacometric analyses are complex and multifactorial. It is essential to check, track, and document the vast amounts of data and metadata that are generated during these analyses (and the relationships between them) in order to comply with regulations, support quality control, auditing, and reporting. It is, however, challenging, tedious, error-prone, and time-consuming, and diverts pharmacometricians from the more useful business of doing science. Automating this process would save time, reduce transcriptional errors, support the retention and transfer of knowledge, encourage good practice, and help ensure that pharmacometric analyses appropriately impact decisions. The ability to document, communicate, and reconstruct a complete pharmacometric analysis using an open standard would have considerable benefits. In this article, the Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe) consortium proposes a set of standards to facilitate the capture, storage, and reporting of knowledge (including assumptions and decisions) in the context of model-informed drug discovery and development (MID3), as well as to support reproducibility: "Thoughtflow." A prototype software implementation is provided. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  20. Absence of association between major vault protein (MVP) gene polymorphisms and drug resistance in Chinese Han patients with partial epilepsy.

    Science.gov (United States)

    Zhou, Luo; Zhang, Mengqi; Long, Hongyu; Long, Lili; Xie, Yuanyuan; Liu, Zhaoqian; Kang, Jin; Chen, Qihua; Feng, Li; Xiao, Bo

    2015-11-15

    Drug resistance in epilepsy is common despite many antiepileptic drugs (AEDs) available for treatment. The development of drug resistant epilepsy may be a result of multiple factors. Several previous studies reported that the major vault protein (MVP) was significantly increased in epileptogenic brain tissues resected from patients with partial-onset seizures, indicating the possible involvement of MVP in drug resistance. In this article, we aimed to identify the association between single nucleotide polymorphisms (SNPs) of MVP gene and drug resistance of partial epilepsy in a Chinese Han population. A total of 510 patients with partial-onset seizures and 206 healthy controls were recruited. Among the patients, 222 were drug resistant and 288 were responsive. The selection of tagging SNPs was based on the Hapmap database and Haploview software and the genotyping was conducted on the Sequenom MassARRAY iPLEX platform. For the selected loci rs12149746, rs9938630 and rs4788186 in the MVP gene, there was no significant difference in allele or genotype distribution between the drug resistant and responsive groups, or between all of the patients and healthy controls. Linkage disequilibrium between any two loci was detected but there was no significant difference in haplotype frequency between the drug resistant and responsive groups. Our results suggest that MVP genetic polymorphisms and haplotypes may not be associated with drug resistance of partial epilepsy in the Chinese Han population. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Directory of Open Access Journals (Sweden)

    Dubravka Svob Strac

    2016-11-01

    Full Text Available A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions and comorbid psychiatric disorders commonly seen in people with epilepsy. However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine and melatonin in epilepsy. Recent experimental, clinical and genetic evidence, will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of one-molecule-one-target, have turned out to be effective only in a percentage of people with epilepsy. Although no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins present on both neurons and glia cells may represent a new approach in the management of seizures and their generation as well as comorbid neuropsychiatric disorders.

  2. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    Science.gov (United States)

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

  3. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.

    Science.gov (United States)

    Devinsky, Orrin; Cross, J Helen; Laux, Linda; Marsh, Eric; Miller, Ian; Nabbout, Rima; Scheffer, Ingrid E; Thiele, Elizabeth A; Wright, Stephen

    2017-05-25

    The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. Among patients with

  4. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  5. Epilepsy - overview

    Science.gov (United States)

    ... or antiepileptic drugs), may reduce the number of future seizures: These drugs are taken by mouth. Which ... 23986299 . Wiebe S. The epilepsies. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...

  6. The worldwide trend of using botanical drugs and strategies for developing global drugs.

    Science.gov (United States)

    Ahn, Kyungseop

    2017-03-01

    Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].

  7. Practitioner Review: Use of Antiepileptic Drugs in Children

    Science.gov (United States)

    Guerrini, Renzo; Parmeggiani, Lucio

    2006-01-01

    Background: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. Methods: Review of data…

  8. Antiepileptic drug prescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel; Garne, Ester; Wang, Hao

    2015-01-01

    and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. Results In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy...... co-prescribed with high-dose folic acid: ranging from 1.0% (CI950.3–1.8%) in Emilia Romagna to 33.5% (CI9528.7–38.4%) in Wales. Conclusion The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co......-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care....

  9. A novel high sensitivity HPLC assay for topiramate, using 4-chloro-7-nitrobenzofurazan as pre-column fluorescence derivatizing agent.

    Science.gov (United States)

    Bahrami, Gholamreza; Mohammadi, Bahareh

    2007-05-01

    A new, sensitive and simple high-performance liquid chromatographic method for analysis of topiramate, an antiepileptic agent, using 4-chloro-7-nitrobenzofurazan as pre-column derivatization agent is described. Following liquid-liquid extraction of topiramate and an internal standard (amlodipine) from human serum, derivatization of the drugs was performed by the labeling agent in the presence of dichloromethane, methanol, acetonitrile and borate buffer (0.05 M; pH 10.6). A mixture of sodium phosphate buffer (0.05 M; pH 2.4): methanol (35:65 v/v) was eluted as mobile phase and chromatographic separation was achieved using a Shimpack CLC-C18 (150 x 4.6 mm) column. In this method the limit of quantification of 0.01 microg/mL was obtained and the procedure was validated over the concentration range of 0.01 to 12.8 microg/mL. No interferences were found from commonly co-administrated antiepileptic drugs including phenytoin, phenobarbital carbamazepine, lamotrigine, zonisamide, primidone, gabapentin, vigabatrin, and ethosuximide. The analysis performance was carried-out in terms of specificity, sensitivity, linearity, precision, accuracy and stability and the method was shown to be accurate, with intra-day and inter-day accuracy from -3.4 to 10% and precise, with intra-day and inter-day precision from 1.1 to 18%.

  10. MDR-1 and MRP2 gene polymorphisms in Mexican epileptic pediatric patients with complex partial seizures.

    Directory of Open Access Journals (Sweden)

    David eEscalante-Santiago

    2014-10-01

    Full Text Available Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1 / ABCB1 and MRP2 / ABCC2 in patients with antiepileptic-drugs resistant epilepsy is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with antiepileptic-drugs resistant epilepsy (ADR and patients with good response to anti-epileptic drugs (CTR in a rigorously selected population. We analyzed 22 samples from drug-resistant patients with epilepsy and 7 samples from patients with good response to anti-epileptic drugs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA and rs2032582 (AT and AG were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT and 66744T>A (TG were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with AED-resistant epilepsy.

  11. Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability.

    Science.gov (United States)

    Sitges, María; Chiu, Luz María; Reed, Ronald C

    2016-04-01

    Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated.

  12. Epilepsy during pregnancy: focus on management strategies

    Directory of Open Access Journals (Sweden)

    Borgelt LM

    2016-09-01

    Full Text Available Laura M Borgelt,1 Felecia M Hart,2 Jacquelyn L Bainbridge2 1Departments of Clinical Pharmacy and Family Medicine, 2Departments of Clinical Pharmacy and Neurology, University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA Abstract: In the US, more than one million women with epilepsy are of childbearing age and have over 20,000 babies each year. Patients with epilepsy who become pregnant are at risk of complications, including changes in seizure frequency, maternal morbidity and mortality, and congenital anomalies due to antiepileptic drug exposure. Appropriate management of epilepsy during pregnancy may involve frequent monitoring of antiepileptic drug serum concentrations, potential preconception switching of antiepileptic medications, making dose adjustments, minimizing peak drug concentration with more frequent dosing, and avoiding potentially teratogenic medications. Ideally, preconception planning will be done to minimize risks to both the mother and fetus during pregnancy. It is important to recognize benefits and risks of current and emerging therapies, especially with revised pregnancy labeling in prescription drug product information. This review will outline risks for epilepsy during pregnancy, review various recommendations from leading organizations, and provide an evidence-based approach for managing patients with epilepsy before, during, and after pregnancy. Keywords: epilepsy, teratogens, anticonvulsants, medication therapy management

  13. A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood.

    Science.gov (United States)

    Yang, Zhixian; Liu, Xiaoyan; Qin, Jiong; Zhang, Yuehua; Bao, Xinhua; Chang, Xingzhi; Wang, Shuang; Wu, Ye; Xiong, Hui

    2009-04-01

    To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient's arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient's arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.

  14. International veterinary epilepsy task force consensus proposal

    DEFF Research Database (Denmark)

    De Risio, Luisa; Bhatti, Sofie; Muñana, Karen

    2015-01-01

    years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose...

  15. Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking phenytoin and levetiracetam: a case report

    Directory of Open Access Journals (Sweden)

    Hall David Jeffrey

    2013-01-01

    Full Text Available Abstract Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. Case presentation We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Conclusion Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.

  16. Neglected simultaneous bilateral femoral neck fractures secondary to narcotic drug abuse treated by bilateral one-staged hemiarthroplasty: a case report

    Directory of Open Access Journals (Sweden)

    Vahedi Ehsan

    2010-06-01

    Full Text Available Abstract Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid or renal dysfunction, anti-epileptic medications, seizure, etc. A 28-year-old addict man referred to us with a 10-year history of narcotic drug abuse and history of 8 months bilateral groin pain. He admitted with displaced bilateral femoral neck fracture. Because of long duration of this condition and osteonecrosis revealed on bone scan, one-staged bilateral hip hemiarthroplasty was done. A good function was noted after surgery to 4-month follow up. Up to now, have not be founded in the literature that a case of bilateral femoral neck fracture associated with narcotic drug abuse. Because of negative effects of opium or smoking on bone tissues, a simple bone pain should aware us about the risk of stress or fatigue fracture.

  17. Combining non-pharmacological treatments with pharmacotherapies for neurological disorders: a unique interface of the brain, drug-device, and intellectual property.

    Science.gov (United States)

    Bulaj, Grzegorz

    2014-01-01

    Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug-device therapies may be offset by a value proposition of the exclusivity due to the patent-independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries.

  18. Combining Non-pharmacological Treatments with Pharmacotherapies for Neurological Disorders: a Unique Interface of the Brain, Drug-Device and Intellectual Property

    Directory of Open Access Journals (Sweden)

    Grzegorz eBulaj

    2014-07-01

    Full Text Available Mobile medical applications (mHealth, music and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engage an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug-device therapies may be offset by a value proposition of the exclusivity due to the patent-independent protection which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies, and their combinations with pharmacotherapies, offers incentives to chronically-ill patients and outcome-driven health care industries.

  19. Drug Information in Space Medicine

    Science.gov (United States)

    Bayuse, Tina M.

    2009-01-01

    Published drug information is widely available for terrestrial conditions. However, information on dosing, administration, drug interactions, stability, and side effects is scant as it relates to use in Space Medicine. Multinational crews on board the International Space Station present additional challenges for drug information because medication nomenclature, information available for the drug as well as the intended use for the drug is not standard across countries. This presentation will look at unique needs for drug information and how the information is managed in Space Medicine. A review was conducted of the drug information requests submitted to the Johnson Space Center Pharmacy by Space Medicine practitioners, astronaut crewmembers and researchers. The information requested was defined and cataloged. A list of references used was maintained. The wide range of information was identified. Due to the information needs for the medications in the on-board medical kits, the Drug Monograph Project was created. A standard method for answering specific drug information questions was generated and maintained by the Johnson Space Center Pharmacy. The Drug Monograph Project will be presented. Topic-centered requests, including multinational drug information, drug-induced adverse reactions, and medication events due to the environment will be highlighted. Information management of the drug information will be explained. Future considerations for drug information needs will be outlined.

  20. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero.

    Science.gov (United States)

    Arulmozhi, T; Dhanaraj, M; Rangaraj, R; Vengatesan, A

    2006-03-01

    To evaluates the physical growth and psychomotor development of infants born to women with epilepsy on regular Anti Epileptic Drugs (AEDs). Govt. Stanley Medical College and Hospital, Tertiary care referral centre, Chennai. Open prospective cohort study with a control group. Consecutive women with epilepsy who were on regular anticonvulsants were followed up from their first trimester. Their babies were examined at birth and anthropometric measurements including anterior fontanelle size were noted. They were followed up till one year and periodically evaluated at 1st, 6th and 12th month of age. Development testing using Griffith scale was done at 2nd, 6th and 12th month. An equal number of control babies were also studied using the same scale for one year at the specified intervals. The results in both the groups were compared. 30 babies were enrolled in the case and control group. The AEDs received by the mothers with epilepsy were Phenytoin, Carbamazepine, and Sodium valproate. At birth and 1st month the weight, head circumference and length of case and control babies were equal. At 6th and 12th month reduction in the above 3 parameters were noted in the case babies ( P < 0.01). Area of anterior fontanelle (AF) was larger in the study group particularly in those exposed to phenytoin in utero (P < 0.001). In the case babies reduction in the sitting, prone and erect progression of the locomotor scores was observed at 2nd month (P < 0.001). Prone progression alone improved by 12th month and other two remained less than the control (P < 0.001). No difference was observed in reaching behaviour and personal/social scores in both groups. Infants exposed to Phenytoin monotherapy had a negative impact on sitting progression. Among infants exposed to AEDs in utero physical growth was equal to that of control at birth but reduced at 6th and 12th month probably due to extraneous factors. The Locomotor scores showed reduction in all areas in 2nd, 6th and 12th month except

  1. Neuroendocrine considerations in the treatment of men and women with epilepsy

    Science.gov (United States)

    Harden, Cynthia L; Pennell, Page B

    2016-01-01

    Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy. PMID:23237902

  2. Hospitalized pediatric antituberculosis drug induced hepatotoxicity: Experience of an Indonesian referral hospital

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2017-05-01

    Full Text Available Objective: To determine the characteristics and risk factors of pediatric antituberculosis drug induced hepatotoxicity (ADIH in Dr. Hasan Sadikin Hospital, a referral hospital in West Java, Indonesia. Methods: Medical records of hospitalized pediatric ADIH from October 2010 to October 2015 were reviewed retrospectively through computer-based search. Descriptive data were presented as percentage. Analytical case-control study on characteristics of ADIH was conducted using Chi-square and Mann Whitney test. Results: Fifty (3.5% out of 1 424 pediatric TB patients developed ADIH; 20 (40% were boys and 30 (60% girls. More than half were under 5 years old and 33 (66% were malnourished. ADIH occured in 29 (58% cases treated for pulmonary TB, 15 (30% for extrapulmonary TB and 6 (12% for both; 34 cases (68% occured during the intensive phase. We identified hepatic comorbidities including CMV infection [1 (2%] and typhoid [1 (2%], and other diseases treated by hepatotoxic drugs such as chemotherapeutic drugs, antiepileptics, and antiretroviral drugs [9 (18%]. Case-control analysis of 50 ADIH cases and 100 TB controls without ADIH showed that the correlation between gender, age, type of TB, nutritional status and comorbidities to occurence of ADIH was statistically insignificant (P = 0.26, 0.765, 0.495, 0.534 9 and 0.336, respectively. Pediatric ADIH was treated using modified British Thoracic Society guidelines. Conclusions: Pediatric ADIH in our hospital is quite frequent, thus identifying risk factors and development of pediatric guideline is mandatory. Further study is needed to identify other risk factors such as genetic acetylator status.

  3. Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

    Science.gov (United States)

    Walsh, Jordana; Thomas, Rhys H; Church, Carla; Rees, Mark I; Marson, Anthony G; Baker, Gus A

    2014-06-01

    The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery. Copyright © 2014. Published by Elsevier Inc.

  4. Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

    Science.gov (United States)

    Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

    2017-10-03

    The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

  5. Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

    Science.gov (United States)

    Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

    2018-03-09

    Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

  6. Physicochemical and phytochemical standardization of berries of Myrtus communis Linn.

    Directory of Open Access Journals (Sweden)

    Sabiha Sumbul

    2012-01-01

    Full Text Available Purpose: Herbal medicines are gaining more and more attention all over the world due to their long historical clinical practice and less side effects. The major limitation with herbal medicines is that the lack of standardization technique. Initially, the crude drugs were identified by comparison only with the standard description available. Materials and Methods: Standardization of drugs means confirmation of its identity and determination of its quality and purity. The quality control standards of various medicinal plants, used in indigenous system of medicine, are significant nowadays in view of commercialization of formulations based on medicinal plants. The quality of herbal drugs is the sum of all factors, which contribute directly or indirectly to the safety, effectiveness, and acceptability of the product. Lack of quality control can affect the efficacy and safety of drugs that may lead to health problems in the consumers. Standardization of drugs is needed to overcome the problems of adulteration and is most developing field of research now. Therefore, there is an urgent need of standardized drugs having consistent quality. Results: The drug showed the presence of phyto-chemical constituents. Powdered drug was treated with different reagents and examined under UV light. Different reagents showed different colors of the drug at 2 wavelengths. The percentage of physiological active compounds viz. total phenolics, tannins, volatile oil, fixed oil, and alkaloids were also observed. Conclusion: Myrtus communis L. (Family: Myrtaceae is one of the important drug being used in Unani system of medicine for various therapeutic purposes. In this study, an attempt has been made to study berries of M. communis from physico-chemical and phytochemical standardization point of view.

  7. Standards for labelling and storage of anaesthetic medications--an audit.

    Science.gov (United States)

    Imran, Muhammad; Khan, Fauzia Anis; Abbasi, Shemila

    2009-12-01

    To check compliance of anaesthetist to current policies set for the use of medication within operation room and for induction room floor stock. The initial audit was conducted from 1st October to 31st November 2006 and reaudit after dissemination and sharing of results within the department repeated in July-August 2007. In each audit four operating rooms were visited twice a week. Syringes were checked for standard drug labelling for narcotic and non narcotic preparations. Drug trolley was checked for any expired drugs and whether the trolley was locked in case of operating room (OR) where list was ended or was on hold. Any unattended drug was noted and Induction room was checked twice weekly for accurate drug inventory and for standard drug storage recommendations. Labels were according to standard in non narcotic drugs on 25% syringes in first audit and 63% in second audit, likewise, narcotics labels were according to standards in 41% in first and 57% in second audit. Unattended drugs were present once in first and twice in second audit. There was 100% compliance in other drug storage policy parameters in both audits. Poor compliance of drug labelling standards for both narcotic and non narcotic drugs was present. However, second audit revealed improvement in all areas of drug handling. Dissemination of policies and reminders are important for continuing improvement in use of medication within operation room and within induction room floor stock.

  8. Food and Drug Administration Drug Approval Process: A History and Overview.

    Science.gov (United States)

    Williams, Christopher Ty

    2016-03-01

    In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Epilepsy treatment. Targeting LDH enzymes with a stiripentol analog to treat epilepsy.

    Science.gov (United States)

    Sada, Nagisa; Lee, Suni; Katsu, Takashi; Otsuki, Takemi; Inoue, Tsuyoshi

    2015-03-20

    Neuronal excitation is regulated by energy metabolism, and drug-resistant epilepsy can be suppressed by special diets. Here, we report that seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), a component of the astrocyte-neuron lactate shuttle. Inhibition of the enzyme LDH hyperpolarized neurons, which was reversed by the downstream metabolite pyruvate. LDH inhibition also suppressed seizures in vivo in a mouse model of epilepsy. We further found that stiripentol, a clinically used antiepileptic drug, is an LDH inhibitor. By modifying its chemical structure, we identified a previously unknown LDH inhibitor, which potently suppressed seizures in vivo. We conclude that LDH inhibitors are a promising new group of antiepileptic drugs. Copyright © 2015, American Association for the Advancement of Science.

  10. Levetiracetam for the Treatment of Refractor Neonatal Seizures

    Directory of Open Access Journals (Sweden)

    Esengül KELEŞ

    2012-01-01

    Full Text Available Convulsions are observed commonly in newborns and especially in premature babies. The afety and efficiency of conventional antiepileptic drugs have been extensively investigated. But long term side effects like apoptosis are newly recognized even with the the most commonly used antiepilectic drug, phenobarbital. Much research is related to the safety and efficiency of levetiracetam, one of the recent antiepileptic drugs, used in partial onset idiopathic or generalized seizures of adults and children. However, research on newborns, especially premature newborns is limited. In this paper we present two cases involving seven day newborn premature twins treated with refractory seizures. Seizures were controlled only with levetiracetam therapy. We did not observe any long term side effects which can be related to levetiracetam or seizures in a long term follow up of both patients.

  11. Bijwerkingen van anti-epileptica en convulsies als bijwerkingen : Medicamenten en epilepsie

    NARCIS (Netherlands)

    Diemont, W.L.; Van Puijenbroek, E.P.; Hekster, Y.A.

    2002-01-01

    The Netherlands Pharmacovigilance Foundation(Lareb) evaluates the reports as generated by the spontaneous adverse event reporting system. This article describes the adverse event profile of antiepileptic drugs, as well as other drugs that may cause seizures that have been reported to Lareb.

  12. Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

    Science.gov (United States)

    Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

    2010-02-01

    A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Prenatal drug exposure and teratological risk: one-year experience of an Italian Teratology Information Service.

    Science.gov (United States)

    De Santis, Marco; Cesari, Elena; Ligato, Maria Serena; Nobili, Elena; Straface, Gianluca; Cavaliere, Annafranca; Caruso, Alessandro

    2008-02-01

    Concern about exposure to drugs, radiation, or infection during pregnancy occur often because pregnancy is not always planned. A teratology information service offers rapid scientific counseling to all those worried about prenatal exposure. The aim of this study is to present data on the most common pharmaceutical products responsible for teratogenic risk in the one-year experience of a teratology information service in Italy. The survey was conducted among 8664 callers who contacted our Teratology Information Service in Rome between January and December 2006. Data on maternal age, gravidity, parity, maternal health status, and details of exposure (dose and timing) were collected and stored in a specific data base. Scientific counseling on prenatal exposure was given to the caller by a specialized service operator, specifying the type of risk and suggesting appropriate tests for prenatal diagnosis. Most of the people called regarding drug exposure; increased risk was present in only 5% of the pregnant women calling during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are the first category that are actually considered of increased risk to the fetus. The second category is represented by antiepileptic drugs. This experience confirms previous data that there is a high teratological risk perception among both women and physicians. The drugs estimated to present increased risk are medications used for chronic neurological diseases, mainly mood disorders and epilepsy. Preconceptional counseling for these women could be an effective strategy to prevent such exposure and to improve maternal and fetal outcome.

  14. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination

    International Nuclear Information System (INIS)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M.; Guwy, Alan J.

    2009-01-01

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs. - Wastewater as an indicative source of information can be used in forensic applications.

  15. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data, Part 2: Pharmaceuticals as chemical markers of faecal water contamination

    Energy Technology Data Exchange (ETDEWEB)

    Kasprzyk-Hordern, Barbara, E-mail: B.Kasprzyk-Hordern@hud.ac.u [University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH (United Kingdom); University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom)

    2009-06-15

    This manuscript is part two of a two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. In this paper pharmaceuticals were investigated as potential chemical indicators of water contamination with sewage. The monitoring program carried out in Wales revealed that some pharmaceuticals are particularly persistent and/or ubiquitous in contaminated river water and therefore might be considered as potential conservative or labile wastewater indicators. In particular, these include some anti-inflammatory/analgesics, antiepileptics, beta-blockers, some H2-receptor antagonists and antibacterial drugs. - Wastewater as an indicative source of information can be used in forensic applications.

  16. A drug's life: the pathway to drug approval.

    Science.gov (United States)

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  17. Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Geng H

    2017-03-01

    Full Text Available Hua Geng, Chengzhong Wang Department of Pediatrics, Maternal and Child Health Hospital of Yancheng, Yancheng City, People’s Republic of China Background: To assess the efficacy and safety of oxcarbazepine (OXC in the treatment of children with epilepsy.Methods: Randomized controlled trials (RCTs published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China, and Chinese National Knowledge Infrastructure (China database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR with 95% confidence intervals (95% CIs was calculated using fixed-effects or random-effects model.Results: Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo, OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P=0.366 and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P=0.310; for 50%–75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P=0.301; for <50% reduction: RR =0.79, 95% CI: 0.56, 1.12; P=0.179. Moreover, patients treated with OXC had a comparable incidence of adverse events compared with those treated with other antiepileptic drugs (RR =1.01, 95% CI: 0.92, 1.11; P=0.760.Conclusion: OXC showed similar effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings. Keywords: epilepsy, children, oxcarbazepine, meta-analysis

  18. Availability and cost of major and first-line antiepileptic drugs: a comprehensive evaluation in the capital of Madagascar.

    Science.gov (United States)

    Jost, Jeremy; Raharivelo, Adeline; Ratsimbazafy, Voa; Nizard, Mandy; Auditeau, Emilie; Newton, Charles R; Preux, Pierre-Marie

    2016-01-01

    The prevalence of epilepsy is high in Madagascar (23.5/1000), as is the treatment gap (estimated at 92 %). The health system of the country is underfunded; some AEDs are used, and the national drug policy does not encourage price regulation or the administration of generic agents. We conducted a cross-sectional study to assess the availability and cost of solid oral AED formulations in Antananarivo, capital of Madagascar. Data were gathered from all officially registered pharmacies (according to the drug agency list, updated in 2015) by means of telephone interviews lasting no more than 10 min and conducted by a native Malagasy speaker. With regard to other sources (hospitals, illicit sales) data were obtained at specific visits. The study received ethical approval from the Madagascar Ministry of Health. A total of 91 of 100 pharmacies (the nine not included were because of an inoperative phone number), two of three public hospitals, and two illegal outlets were investigated. Sodium valproate was available in 84.6 % of the pharmacies, while carbamazepine and phenobarbital were available in 68.1 % and 36.3 % of the pharmacies, respectively, but phenytoin was not available in any supply chain. There were more originator brands than generic formulations, with a higher cost (range 20.3-81.1 %, median 40.7 %) compared to the equivalent generic. The public system had only a very limited choice of AED, but offered the lowest costs. Illicit sources were more expensive by 54.3 % for carbamazepine and 62.5 % for phenobarbital. Concerning the annual cost of treatment, the average percentage of the gross national income per capita based on the purchasing power parity was 29.8 %/19.0 % (brand/generic) for sodium valproate, 16.4 %/7.3 % (brand/generic) for carbamazepine, 8.9 %/5.1 % (brand/generic) for phenobarbital. The main sources of AEDs were private pharmacies, but the stocks held were low. The financial burden was still important in the capital of Madagascar

  19. Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

    Science.gov (United States)

    Balestrini, Simona; Clayton, Lisa M S; Bartmann, Ana P; Chinthapalli, Krishna; Novy, Jan; Coppola, Antonietta; Wandschneider, Britta; Stern, William M; Acheson, James; Bell, Gail S; Sander, Josemir W; Sisodiya, Sanjay M

    2016-04-01

    Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient -0.16, p=0.004) and presence of intellectual disability (coefficient -4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. THE EFFICACY AND SAFETY OF OXCARBAZEPINE AS ADD-ON THERAPY IN INTRACTABLE EPILEPSY IN CHILDREN

    OpenAIRE

    Azita TAVASSOLI; Mohammad GHOFRANI; Mohsen ROUZROKH; Eznollah AZARGASHB

    2010-01-01

    Objective1-3% of the population suffer from epilepsy. Up to 30% of them develop refractory epilepsy and their seizures occur more than once per month despite receiving at least 2 first line antiepileptic drugs. In  this group, more efficacious antiepileptics are needed. This study was undertaken to evaluate the efficacy and safety of Oxcarbazepine as an adjunction therapy in children with refractory epilepsy.Materials & MethodsFrom Feb 2004 until Sep 2006, 30 patients with refractory epilepsy...

  1. Automatic Detection of Childhood Absence Epilepsy Seizures: Toward a Monitoring Device

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Madsen, Rasmus E.; Remvig, Line S.

    2012-01-01

    Automatic detections of paroxysms in patients with childhood absence epilepsy have been neglected for several years. We acquire reliable detections using only a single-channel brainwave monitor, allowing for unobtrusive monitoring of antiepileptic drug effects. Ultimately we seek to obtain optimal...... long-term prognoses, balancing antiepileptic effects and side effects. The electroencephalographic appearance of paroxysms in childhood absence epilepsy is fairly homogeneous, making it feasible to develop patient-independent automatic detection. We implemented a state-of-the-art algorithm...

  2. Precipitants of seizure among patients with epilepsy: Experience at Kano, Northwestern Nigeria

    Directory of Open Access Journals (Sweden)

    L F Owolabi

    2012-01-01

    Conclusion: Common precipitating factors of seizure included stress, febrile illness and non adherence to antiepileptic drugs. Knowledge of these precipitating factors are vital prevention of seizure.

  3. Epilepsy & IQ: the clinical utility of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) indices in the neuropsychological assessment of people with epilepsy.

    Science.gov (United States)

    Baxendale, Sallie; McGrath, Katherine; Thompson, Pamela J

    2014-01-01

    We examined Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) General Ability Index (GAI) and Full Scale Intelligence Quotient (FSIQ) discrepancies in 100 epilepsy patients; 44% had a significant GAI > FSIQ discrepancy. GAI-FSIQ discrepancies were correlated with the number of antiepileptic drugs taken and duration of epilepsy. Individual antiepileptic drugs differentially interfere with the expression of underlying intellectual ability in this group. FSIQ may significantly underestimate levels of general intellectual ability in people with epilepsy. Inaccurate representations of FSIQ due to selective impairments in working memory and reduced processing speed obscure the contextual interpretation of performance on other neuropsychological tests, and subtle localizing and lateralizing signs may be missed as a result.

  4. Association Between Prenatal Valproate Exposure and Performance on Standardized Language and Mathematics Tests in School-aged Children

    DEFF Research Database (Denmark)

    Elkjær, Lars Skou; Bech, Bodil Hammer; Sun, Yuelian

    2018-01-01

    by Statistics Denmark on April 15, 2016. All children born alive in Denmark between 1997 and 2006 (n = 656 496) were identified. From this cohort, children who did not participate in the national tests, with presumed coding errors in gestational age and children missing information on their mother's educational......Importance: Valproate sodium is used for the treatment of epilepsy and other neuropsychiatric disorders in women of childbearing potential. However, there are concerns about impaired cognitive development in children who have been exposed to valproate during pregnancy. Objective: To estimate...... the association between long-term school performance and prenatal exposure to valproate and a number of other antiepileptic drugs (AEDs). Design, Setting, and Participants: In a prospective, population-based cohort study conducted from August 1, 2015, to May 31, 2017, data used in the study were provided...

  5. Refractory status epilepticus

    Directory of Open Access Journals (Sweden)

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  6. Refractory status epilepticus

    Science.gov (United States)

    Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

    2014-01-01

    Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

  7. Prophylactic drug management for febrile seizures in children

    NARCIS (Netherlands)

    Offringa, Martin; Newton, Richard

    2013-01-01

    BACKGROUND Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the

  8. Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Geng, Hua; Wang, Chengzhong

    2017-01-01

    To assess the efficacy and safety of oxcarbazepine (OXC) in the treatment of children with epilepsy. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China), and Chinese National Knowledge Infrastructure (China) database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR) with 95% confidence intervals (95% CIs) was calculated using fixed-effects or random-effects model. Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo), OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P =0.366) and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P =0.310; for 50%-75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P =0.301; for effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings.

  9. Nonpharmacological treatment of epilepsy

    Directory of Open Access Journals (Sweden)

    V S Saxena

    2011-01-01

    Full Text Available Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine. Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70-80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment.

  10. 21 CFR 862.3660 - Phenobarbital test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Phenobarbital test system. 862.3660 Section 862....3660 Phenobarbital test system. (a) Identification. A phenobarbitol test system is a device intended to measure phenobarbital, an antiepileptic and sedative-hypnotic drug, in human specimens. Measurements...

  11. 73_368 - 371_BIO 021 Mustapha

    African Journals Online (AJOL)

    userpc

    New York. Pp. 85-103. WHO (2016). Epilepsy: WHO Fact Sheets. Retrieved 22nd May 2016. Wickenden, A.D. (2002). Potassium channels as antiepileptic drug targets. Neuropharmacology, 43: 1055-1060. Yamaguchi, S., and Rogawski, M.A. (1992). Effects of Anticonvulsant Drugs on 4- aminopyridine-Induced Seizures in.

  12. FUNCTIONAL ELECTRICAL STIMULATION FOR CONTROL OF EPILEPTIC SEIZURES

    DEFF Research Database (Denmark)

    Jiao, Jianhang

    Nearly 50 million people worldwide have epilepsy and one-third of them do not respond well to any antiepileptic drugs. Given the large population of patients experiencing drug resistant epilepsy, increased attention has been paid over the last two decades to the development of electrical stimulat...

  13. HYDROXYCARBAMINE: FROM AN OLD DRUG USED IN MALIGNANT HEMOPATHIES TO A CURRENT STANDARD IN SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Giovanna Cannas

    2017-02-01

    Full Text Available While hydroxycarbamine (hydroxyurea, HU has less and less indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support of safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. HU has become the standard-of-care for sickle cell anemia, but remains underused. Barriers to its use should be identified and overcome.

  14. Prophylactic drug management for febrile seizures in children

    NARCIS (Netherlands)

    Offringa, Martin; Newton, Richard

    2012-01-01

    Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects

  15. [Standardization of names in prescriptions of traditional Chinese medicines].

    Science.gov (United States)

    Li, Chao-Feng; Zhang, Yu-Jun; Fan, Dong-He; Zhang, Meng-Jie; Bai, Xue; Yang, Wen-Hua; Qi, Shu-Ya; Zhang, Zhi-Jie; Xue, Chun-Miao; Mao, Liu-Ying; Cao, Jun-Ling

    2017-01-01

    Chinese medicine prescriptions are a type of medical documents written by doctors after they understand the patients' conditions for syndrome differentiation. Chinese medicine prescriptions are also the basis for pharmacy personnel to dispense medicines and guide patients to use drugs. It has the legal, technical and economic significances. Chinese medicine prescriptions contain such information of names, quantity and usage. Whether the names of drugs in Chinese medicine prescriptions are standardized or not is directly related to the safety and efficacy of the drugs. At present, nonstandard clinical prescriptions are frequently seen. With "Chinese medicine prescription", "names of drug in Chinese medicine prescription" and "standards of Chinese medicine prescription" as key words, the author searched CNKI, Wanfang and other databases, and consulted nearly 100 literatures, so as to summarize current names of drugs in traditional Chinese medicine prescription, analyze the reasons, and give suggestions, in the expectation of standardizing the names of drugs used in traditional Chinese medicine prescriptions. Copyright© by the Chinese Pharmaceutical Association.

  16. Purely in silico BCS classification: science based quality standards for the world's drugs.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Kim, Young Hoon; Ramachandran, Chandrasekharan; Crippen, Gordon M; Takagi, Toshihide; Bermejo, Marival; Amidon, Gordon L

    2013-11-04

    BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contribution (CLogP) and atom contribution (ALogP) methods, and a new method based solely on the molecular formula and element contribution (KLogP). Metoprolol was used as the benchmark for the low/high permeability class boundary. Solubility was estimated in silico using a thermodynamic equation that relies on the partition coefficient and melting point. The validity of each method was affirmed by comparison to reference data and literature. We then used each method to provisionally classify the orally administered, IR drug products found in the WHO Model list of Essential Medicines, and the top-selling oral drug products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL), Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from the various lists, and 257 drugs were classified using the different in silico permeability methods and literature solubility data, as well as BDDCS classification. Lastly, we calculated the solubility values for 185 drugs from the combined set using in silico approach. Permeability classification with the different in silico methods was correct for 69-72.4% of the 29 reference drugs with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference drugs in the set. The correlations (r(2)) between experimental log P values of 154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71, respectively. The different in silico permeability methods produced comparable results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4% were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ∼8% could not be classified. The WHO list

  17. The Importance of Prolonged Provocation in Drug Allergy

    DEFF Research Database (Denmark)

    Fransson, Sara; Mosbech, Holger; Kappel, Mogens

    2017-01-01

    BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug...

  18. Drug and alcohol task force

    International Nuclear Information System (INIS)

    Gordey, T.; Sunstrum, M.

    2006-01-01

    Worker absenteeism due to substance abuse costs the Alberta economy approximately $720 million a year. It is estimated that 20 per cent of all drivers in fatal crashes were using alcohol, and the use of cannabis and cocaine in Alberta has more than doubled over the last 15 years. In addition, 1 in 10 Alberta workers have reported using alcohol while at work and 4 per cent have reported using alcohol 4 hours prior to coming to work during the previous 12 months. In an effort to ensure appropriate health and safety for workers in the Canadian petroleum industry, 6 trade associations in the sector have joined together as the Enform Alcohol and Drug Initiative and are now working to develop a common approach to drug and alcohol guidelines and workplace rules. The task group will determine if existing policies and guidelines are sufficient to ensure a safe workplace and will consider standardizing the testing, application and rehabilitation of workers with respect to the use of drugs and alcohol. In the past, disciplinary actions have often been reversed because employers have not been consistent or did not follow established alcohol and drug policies or test to specific standards. Various work rules for inappropriate alcohol and drug use were reviewed, as well as education and communication strategies regarding policy content. Standards for testing criteria were discussed, as well as issues concerning duty-to-accommodate circumstances. An excerpt of concentration standards was presented. It was concluded that a matrix for companies to assess and determine safety sensitive positions is needed. refs., tabs., figs

  19. Drug and alcohol task force

    Energy Technology Data Exchange (ETDEWEB)

    Gordey, T [ConocoPhillips Canada Resources Corp., Calgary, AB (Canada); Sunstrum, M [Enform, Calgary, AB (Canada)

    2006-07-01

    Worker absenteeism due to substance abuse costs the Alberta economy approximately $720 million a year. It is estimated that 20 per cent of all drivers in fatal crashes were using alcohol, and the use of cannabis and cocaine in Alberta has more than doubled over the last 15 years. In addition, 1 in 10 Alberta workers have reported using alcohol while at work and 4 per cent have reported using alcohol 4 hours prior to coming to work during the previous 12 months. In an effort to ensure appropriate health and safety for workers in the Canadian petroleum industry, 6 trade associations in the sector have joined together as the Enform Alcohol and Drug Initiative and are now working to develop a common approach to drug and alcohol guidelines and workplace rules. The task group will determine if existing policies and guidelines are sufficient to ensure a safe workplace and will consider standardizing the testing, application and rehabilitation of workers with respect to the use of drugs and alcohol. In the past, disciplinary actions have often been reversed because employers have not been consistent or did not follow established alcohol and drug policies or test to specific standards. Various work rules for inappropriate alcohol and drug use were reviewed, as well as education and communication strategies regarding policy content. Standards for testing criteria were discussed, as well as issues concerning duty-to-accommodate circumstances. An excerpt of concentration standards was presented. It was concluded that a matrix for companies to assess and determine safety sensitive positions is needed. refs., tabs., figs.

  20. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  1. A descriptive analysis of drug treatment patterns and burden of illness for pediatric patients diagnosed with partial-onset seizures in the USA

    Directory of Open Access Journals (Sweden)

    Angalakuditi M

    2011-12-01

    Full Text Available Mallik Angalakuditi1, Nupur Angalakuditi21Georgia State University, Robinson School of Business, Atlanta, GA, 2New York Medical College, Valhalla, NY, USAPurpose: The objective of this retrospective claims study was to describe antiepileptic drug (AED treatment patterns and burden of illness in children with epilepsy.Methods: Data were administrative claims from a US commercial health plan. Patients were between 2 and 17 years of age and had one or more pharmacy claims for an oral AED from July 1, 2005, to November 30, 2009. The index date was defined as the first AED claim. Patients had one or more medical claims for epilepsy (ICD-9-CM 345.xx during the 6-month pre-index period and were continuously enrolled for 12 months post index. Of the 17 AED medications used to identify patients, eleven medication cohorts had more than 100 patients: (1 carbamazepine (CAR; (2 clonazepam; (3 gabapentin (GAB; (4 lamotrigine (LAM; (5 levetiracetam (LEV; (6 oxcarbazepine (OXC; (7 phenobarbital; (8 phenytoin (PHY; (9 topiramate (TOP; (10 valproate (VAL; and (11 zonisamide (ZON.Results: There were 3889 children who met the inclusion criteria. There were some differences in patients across the eleven AED treatment cohorts based on index therapy in age, gender, geographic location, Charlson comorbidity score, AHRQ comorbid conditions, as well as epilepsy-related risk factors and comorbidities. Of the 17 AEDs examined, the most frequently prescribed were OXC (21% and LEV (19%; the least prescribed AED was GAB (1%. Their respective mean post-index pharmacy and total costs were as follows: OXC, US$2095 and US$5556; LEV, US$3025 and US$9121; and GAB, US$917 and US$1597. The overall post-index mean pharmacy costs were US$2637, and mean total costs were US$6813.Conclusion: Study results demonstrate differences in patient demographic and clinical characteristics across AED medication cohorts. Some cohorts have greater odds of a switch, or augmentation than the reference

  2. Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

    Science.gov (United States)

    Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

    2014-08-01

    Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs Densidade mineral óssea e níveis séricos de 25 OH vitamina D em usuários crônicos de drogas antiepilépticas

    Directory of Open Access Journals (Sweden)

    Carolina A.M. Kulak

    2004-12-01

    Full Text Available The aim of this cross sectional study was to evaluate bone mineral density (BMD and serum levels of 25-hydroxy vitamin D (25OHD in a group of patients taking antiepileptic drugs (AED for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men, 34.4±6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime. The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men; 34.2±5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000. Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH and calcium. Unemployment and smoking history were more frequent among patients than among controls (pO objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO e os níveis de 25hidroxi vitamina D (25OHD em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE. Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4±6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia. O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2±5,9 anos. Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram

  4. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  5. Drug shortage management in Alabama hospital pharmacies

    Directory of Open Access Journals (Sweden)

    Oliver W. Holmes, III

    2013-01-01

    Full Text Available Purpose: The purpose of this study is to identify effective strategies used by Alabama hospitals to manage drug shortages. Moreover, this study aims to determine if there are any relationships among hospital size, utilization of a standard policy for drug shortage management and perceived usefulness of standard procedures for drug shortages. Methods: A paper survey was mailed to 129 hospital pharmacies in Alabama (per the Alabama Hospital Association directory. The survey consisted of 5 demographic questions, questions involving perception of current medication shortages, sources of information about shorted drugs, and frequency of discussion at P&T committee meetings. Most importantly, the survey contained questions about the use of a standard policy for handling drug shortages, the effectiveness of the policy if one is used, and an open-ended question asking the recipient to describe the policy being used. Results: A response rate of 55% was achieved as 71 surveys were completed and returned. Approximately 70% of the survey respondents described the current drug shortage issue as a top priority in their pharmacy department. The pharmacy distributor served as the primary source of information regarding drug shortages for 45% of the facilities. There is a direct relationship between size of hospital and likelihood of utilization of a standard policy or procedure for drug shortage management among the sample. The smaller facilities of the sample perceived their management strategies as effective more frequently than the larger hospitals. Conclusion: Common components of effective management strategies included extensive communication of shortage details and the ability to locate alternative products. The use of portable technology (e.g., Smart phones and tablets along with mobile applications may emerge as popular means for communicating drug product shortage news and updates within a facility or healthcare system.   Type: Original Research

  6. Drug shortage management in Alabama hospital pharmacies

    Directory of Open Access Journals (Sweden)

    Oliver W. Holmes III, Pharm.D. Candidate 2013

    2013-01-01

    Full Text Available Purpose: The purpose of this study is to identify effective strategies used by Alabama hospitals to manage drug shortages. Moreover, this study aims to determine if there are any relationships among hospital size, utilization of a standard policy for drug shortage management and perceived usefulness of standard procedures for drug shortages.Methods: A paper survey was mailed to 129 hospital pharmacies in Alabama (per the Alabama Hospital Association directory. The survey consisted of 5 demographic questions, questions involving perception of current medication shortages, sources of information about shorted drugs, and frequency of discussion at P&T committee meetings. Most importantly, the survey contained questions about the use of a standard policy for handling drug shortages, the effectiveness of the policy if one is used, and an open-ended question asking the recipient to describe the policy being used.Results: A response rate of 55% was achieved as 71 surveys were completed and returned. Approximately 70% of the survey respondents described the current drug shortage issue as a top priority in their pharmacy department. The pharmacy distributor served as the primary source of information regarding drug shortages for 45% of the facilities. There is a direct relationship between size of hospital and likelihood of utilization of a standard policy or procedure for drug shortage management among the sample. The smaller facilities of the sample perceived their management strategies as effective more frequently than the larger hospitals.Conclusion: Common components of effective management strategies included extensive communication of shortage details and the ability to locate alternative products. The use of portable technology (e.g., Smart phones and tablets along with mobile applications may emerge as popular means for communicating drug product shortage news and updates within a facility or healthcare system.

  7. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; Hansen, Peter Riis; Erdal, Jesper

    2010-01-01

    . The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam (OR: 2.01, CI: 1.25-3.25), valproate (OR: 2.08, CI: 1.01-4.16), lamotrigine (OR: 3.15, CI: 1.35-7.34) and phenobarbital (OR: 1.96, CI...... that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding. Copyright (C) 2010 John Wiley & Sons, Ltd...

  8. PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings.

    Directory of Open Access Journals (Sweden)

    Monica Puligheddu

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are involved in seizure mechanisms. Hence, nocturnal frontal lobe epilepsy was the first idiopathic epilepsy linked with specific mutations in α4 or β2 nAChR subunit genes. These mutations confer gain of function to nAChRs by increasing sensitivity toward acetylcholine. Consistently, nicotine elicits seizures through nAChRs and mimics the excessive nAChR activation observed in animal models of the disease. Treatments aimed at reducing nicotinic inputs are sought as therapies for epilepsies where these receptors contribute to neuronal excitation and synchronization. Previous studies demonstrated that peroxisome proliferator-activated receptors-α (PPARα, nuclear receptor transcription factors, suppress nicotine-induced behavioral and electrophysiological effects by modulating nAChRs containing β2 subunits. On these bases, we tested whether PPARα agonists were protective against nicotine-induced seizures. To this aim we utilized behavioral and electroencephalographic (EEG experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p. or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2% for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.. Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key regulators of neuronal activity through modulation of nAChRs. These effects might be therapeutically exploited for idiopathic or genetically determined forms of epilepsy where nAChRs play a major role.

  9. Pharmacogenomics in epilepsy.

    Science.gov (United States)

    Balestrini, Simona; Sisodiya, Sanjay M

    2018-02-22

    There is high variability in the response to antiepileptic treatment across people with epilepsy. Genetic factors significantly contribute to such variability. Recent advances in the genetics and neurobiology of the epilepsies are establishing the basis for a new era in the treatment of epilepsy, focused on each individual and their specific epilepsy. Variation in response to antiepileptic drug treatment may arise from genetic variation in a range of gene categories, including genes affecting drug pharmacokinetics, and drug pharmacodynamics, but also genes held to actually cause the epilepsy itself. From a purely pharmacogenetic perspective, there are few robust genetic findings with established evidence in epilepsy. Many findings are still controversial with anecdotal or less secure evidence and need further validation, e.g. variation in genes for transporter systems and antiepileptic drug targets. The increasing use of genetic sequencing and the results of large-scale collaborative projects may soon expand the established evidence. Precision medicine treatments represent a growing area of interest, focussing on reversing or circumventing the pathophysiological effects of specific gene mutations. This could lead to a dramatic improvement of the effectiveness and safety of epilepsy treatments, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Whilst much has been written about epilepsy pharmacogenetics, there does now seem to be building momentum that promises to deliver results of use in clinic. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. [Economic aspects of epilepsy].

    Science.gov (United States)

    Argumosa, A; Herranz, J L

    2000-06-01

    The economic magnitude of epilepsy is determined by its effect on the employment status of the patients, the cost of drug treatment for them and the healthcare system and the repercussion worldwide. Studies of the cost of the disease show that it has economic importance due to the sum of the direct and indirect costs caused by it. In the case of epilepsy, the results of studies in various countries led to the creation of a Commission on Economic Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in Spain may explain the lack of publications on this subject in our country. The percentage of the total cost due to antiepileptic drugs is considerable and will probably increase in the future. The pharmaco-economic evaluation made by cost-benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize costs should serve to use healthcare resources in the most effective manner and justify the rational use of the new antiepileptic drugs. The economic impact of epilepsy is added to the repercussion of the disease itself on the patient and his family. The different distribution of costs in children and adults with epilepsy suggest the need for intervention at an early age to try to reduce the long term economic and personal repercussions. The pharmaco-economic evaluation of the new antiepileptic drugs will make it clear whether their considerable cost is worth paying for their greater effectivity.

  11. Mozart's music in children with drug-refractory epileptic encephalopathies.

    Science.gov (United States)

    Coppola, Giangennaro; Toro, Annacarmela; Operto, Francesca Felicia; Ferrarioli, Giuseppe; Pisano, Simone; Viggiano, Andrea; Verrotti, Alberto

    2015-09-01

    Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozart's compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozart's compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

  13. Vývoj kvalitativně nových látek pro léčbu epilepsie - naděje pro 21. století?

    Czech Academy of Sciences Publication Activity Database

    Kubová, Hana

    2006-01-01

    Roč. 5, - (2006), s. 284-286 ISSN 1335-9592 Institutional research plan: CEZ:AV0Z50110509 Keywords : antiepileptic drugs * pharmacoresistant epilepsy * neuroprotective and antiepileptogenic interventions Subject RIV: ED - Physiology

  14. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats.

    Science.gov (United States)

    Saberi, Mehdi; Rezvanizadeh, Alireza; Bakhtiarian, Azam

    2008-08-22

    The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (PVitex at the dose of 120 mg/kg, induced significant increment in S4L (PVitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.

  15. Neurostimulation, neuromodulation, and the treatment of epilepsies

    Directory of Open Access Journals (Sweden)

    Bolden Lauren B.

    2015-06-01

    Full Text Available Introduction. Neurostimulation and neuromodulation are techniques that may be able to affect the course of epilepsy. In the last 20 years, since the approval of VNS, we have observed a surge of studies assessing the potential of other devices and techniques for the treatment of pharmacoresistant epilepsies including deep brain stimulation (DBS, responsive neurostimulation (RNS, trigeminal nerve stimulation (TNS, transcranial direct current stimulation (tDCS, and repetitive transcranial magnetic stimulation (rTMS. Are these devices and techniques simply another treatment option that can be offered to patients with epilepsy or do they offer specific advantages when compared to the standard antiepileptic drugs (AEDs?

  16. Drug utilization pattern in a pain clinic of a tertiary care teaching hospital in Eastern India

    Directory of Open Access Journals (Sweden)

    Debjyoti Dutta

    2013-01-01

    Full Text Available Background: Patients attend the Pain Clinic with varieties of complains of pain, like low back pain, knee pain, shoulder pain, headache, facial pain, different neuralgias and other neuropathic pain states. They receive a multimodal treatment for their pain, Multimodal pain therapy is an integrated multidisciplinary treatment in small groups with a closely coordinated therapeutic approach. Drugs that are prescribed for treatment are not only NSAIDS or Opioids, but also various groups of adjuvant pain medications like anti-epileptics, antidepressants etc. Aim: To find out the drug utilization pattern in the Pain Clinic of a tertiary care medical college hospital in Eastern India. Materials and Methods: A cross sectional; unicentric study was conducted in the Pain Clinic during April 2013 to June 2013. New patients who were willing to participate in the study were enrolled as per selection criteria. A copy of prescriptions were collected from the patients. The drugs prescription patterns were analyzed. Result: 319 patients were included in this study in three months period and their prescriptions were analyzed. Female patients (222 were more in number than male (97. As single prescription and also as combination therapy, paracetamol was found to be the most frequently prescribed drug. Frequently used adjuvant pain medications were found to be pregabalin (21.63% and amitriptyline (16.92%.. Antacid was commonly prescribed as gastroprotective agent. Among drug combinations paracetamol (325 mg + tramadol (37.5 mg combination was used most frequently. (55.17%. Conclusion: In this uncentric study we found that patacetamol, tramadol, pregabalin and amitriptyline are the commonly used medications in a pain clinic. We need more multi-centric and comparative Indian studies.

  17. Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

    Science.gov (United States)

    Das, Jharana; Singh, Rameshwar; Sharma, Deepak

    2017-05-01

    Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies. To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats. Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na + ,K + -ATPase activity) in both the cortex and the hippocampus. Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na + ,K + -ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions. This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

  18. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    International Nuclear Information System (INIS)

    Kampa, I.S.

    1985-01-01

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  19. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    International Nuclear Information System (INIS)

    Smith, Clyde

    2005-01-01

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  20. Pregabalin Use Among Users of Illicit Drugs: A Cross-Sectional Survey in Southern Germany.

    Science.gov (United States)

    Snellgrove, Brendan J; Steinert, Tilman; Jaeger, Susanne

    2017-10-01

    The antiepileptic drug pregabalin is one of the best-selling pharmaceutical products worldwide. There are increasing concerns about its potential for misuse and dependence especially among patients with former or current substance use disorders (SUDs). Our objective was to clarify the extent and pattern of pregabalin use as well as motives and predictors in this population. We conducted a cross-sectional study with patients on a detoxification ward for illicit drugs at the Center for Psychiatry, Südwürttemberg, Ravensburg in southern Germany from August 2012 until July 2013. We used an extensive questionnaire, part of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) Axis I Disorders (SCID-I) and urine samples. Of the 253 participating patients, 56% had used pregabalin at least once. Of these, 92% had acquired it at least in part from illegal sources. The main motives for the use of pregabalin were the attenuation of opioid withdrawal symptoms, the augmentation of other psychotropic substances, and the psychotropic effects of pregabalin itself. Predictors for pregabalin use were opioid and sedative use as well as younger age. The criteria of dependency according to DSM-IV was met by 11% of pregabalin users and 13% of urine samples were positive for pregabalin. Use of pregabalin is common among users of illicit drugs in large parts of southern Germany, with motives for use, acquisition, and mode of use suggesting misuse. The mode of use, especially intake of high doses and concomitant use of other drugs, poses a serious risk to this population, including the development of dependency.

  1. Evaluation of Drug Quality (III): Determination of Ciprofloxacin ...

    African Journals Online (AJOL)

    user

    Evaluation of Drug Quality (III): Determination of Ciprofloxacin Hydrochloride ... two methods were interpreted in terms of differences in sensitivities of the methods. It was ..... Agency for Food, Drug Administration and. Control ... regulatory standards and specified identity. Therefore drug analysis requires that drugs meet their.

  2. WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

    Science.gov (United States)

    Castillo, Sergio M; Schmidt, Dieter B; White, Sarah; Shukralla, Arif

    2016-11-15

    Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug

  3. POSSIBILITIES FOR ANTIEPILEPTIC DRUGS USE IN THE TREATMENT OF TIC HYPERKINESIS AND TOURETTE SYNDROME IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. P. Zykov

    2016-01-01

    Full Text Available Objective: to evaluate the efficacy of topiramate at a dose of 1–2 mg/kg in 34 patients aged 7–17 with tic hyperkinesis and Tourette syndrome (TS.Materials and methods. We performed clinical evaluation of hyperkinesis severity along with the assessment of somatosensory evoked potentials (SSEP and the analysis of surface electromyography (EMG data prior to treatment initiation and after 6 weeks of therapy. SSEP investigation was carried out in accordance with a standard protocol. Interpeak latencies on the tracks Cp–Fpz (D, S, Cerv6–Fpz (D, S, Erb’i–Erb’c (D, S were evaluated in order to determine the afferentation between relevant brain structures: N9–N13, N13–N20, N9–N20. N20–P23 potentials reflected primary activity of somatosensory cortex. The investigation of tic hyperkinesis was conducted using surface EMG of facial muscles (m. orbicularis oculi, the muscles of the shoulder girdle (m. supraspinatus, and the muscles of the upper extremities (m. flexor digitorum superficialis according to the standard protocol. Interference curve was recorded at rest and after hyperkinesis stimulation with the use of provocative tests. High-amplitude (more than 500 mkV oscillations were considered as burst activity. The severity of clinical manifestations was evaluated using the Yale Global Tic Severity Scale (1989 and the method of tics counting during 20 minutes (V.P. Zykov, 2009. The control group comprised 15 healthy children matched for sex and age.Results. The use of topiramate in patients with chronic motor/vocal tics and TS has significantly decreased the severity of hyperkinesis manifestations, evaluated both by the Yale Global Tic Severity Scale (p < 0,05 and by the method of tics counting during 20 minutes (p < 0,05. It also helped to decrease the prevalence of burst activity in EMG while registering hyperkinesis in different muscle groups. SSEP data showed the normalization of interpeak latency values and the decrease of N20

  4. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  5. Drug-food interaction counseling programs in teaching hospitals.

    Science.gov (United States)

    Wix, A R; Doering, P L; Hatton, R C

    1992-04-01

    The results of a survey to characterize drug-food interaction counseling programs in teaching hospitals and solicit opinions on these programs from pharmacists and dietitians are reported. A questionnaire was mailed to the pharmacy director and the director of dietary services at teaching hospitals nationwide. The questionnaire contained 33 questions relating to hospital characteristics, drug-food interaction counseling programs, and the standard calling for such programs issued by the Joint Commission on Accreditation of Healthcare Organizations. Of 792 questionnaires mailed, 425 were returned (response rate, 53.7). A majority of the pharmacists and dietitians (51.2%) did not consider their drug-food interaction counseling program to be formal; some had no program. The pharmacy department was involved more in program development than in the daily operation of such programs. The most frequent methods of identifying patients for counseling were using lists of patients' drugs and using physicians' orders. A mean of only five drugs were targeted per program. Slightly over half the respondents rated the Joint Commission standard less effective than other standards in its ability to improve patient care. A majority of teaching hospitals did not have formal drug-food interaction counseling programs. Pharmacists and dietitians did not view these programs as greatly beneficial and did not believe that the Joint Commission has clearly delineated the requirements for meeting its standard.

  6. Listening to Epilepsy.

    Science.gov (United States)

    Brunquell, Phillip J.

    1994-01-01

    This paper discusses what epilepsy is and what it is not, defines types of epileptic seizures, identifies epilepsy syndromes, discusses antiepileptic drugs, describes seizure surgery, and examines issues of quality of life. (JDD)

  7. Pan African Medical Journal - Vol 17, No 1 (2014)

    African Journals Online (AJOL)

    ... lesions in a group of sub-Saharan African patients on maintenance hemodialysis ... Perceived barriers to the implementation of Isoniazid preventive therapy for ... Adherence to antiepileptic drugs among children attending a tertiary health ...

  8. Human experimental pain models: A review of standardized methods in drug development

    Directory of Open Access Journals (Sweden)

    K. Sunil kumar Reddy

    2012-01-01

    Full Text Available Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

  9. Drug use trajectory patterns among older drug users

    Directory of Open Access Journals (Sweden)

    Tyndall B

    2011-05-01

    Full Text Available Miriam Boeri, Thor Whalen, Benjamin Tyndall, Ellen BallardKennesaw State University, Department of Sociology and Criminal Justice, Kennesaw GA, USAAbstract: To better understand patterns of drug use trajectories over time, it is essential to have standard measures of change. Our goal here is to introduce measures we developed to quantify change in drug use behaviors. A secondary goal is to provide effective visualizations of these trajectories for applied use. We analyzed data from a sample of 92 older drug users (ages 45 to 65 to identify transition patterns in drug use trajectories across the life course. Data were collected for every year since birth using a mixed methods design. The community-drawn sample of active and former users were 40% female, 50% African American, and 60% reporting some college or greater. Their life histories provided retrospective longitudinal data on the diversity of paths taken throughout the life course and changes in drug use patterns that occurred over time. Bayesian analysis was used to model drug trajectories displayed by innovative computer graphics. The mathematical techniques and visualizations presented here provide the foundation for future models using Bayesian analysis. In this paper we introduce the concepts of transition counts, transition rates and relapse/remission rates, and we describe how these measures can help us better understand drug use trajectories. Depicted through these visual tools, measurements of discontinuous patterns provide a succinct view of individual drug use trajectories. The measures we use on drug use data will be further developed to incorporate contextual influences on the drug trajectory and build predictive models that inform rehabilitation efforts for drug users. Although the measures developed here were conceived to better examine drug use trajectories, the applications of these measures can be used with other longitudinal datasets.Keywords: drug use, trajectory patterns

  10. Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs - provision of due diligence in the treatment process.

    Science.gov (United States)

    Zajdel, Justyna; Zajdel, Radosław

    2013-01-01

    Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on "off-label use". The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug.

  11. Antimalarial drug quality in Africa.

    Science.gov (United States)

    Amin, A A; Kokwaro, G O

    2007-10-01

    There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: 'Antimalarials/analysis'[MeSH] OR 'Antimalarials/standards'[MeSH] AND 'Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine-pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the

  12. Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy.

    Science.gov (United States)

    Pulido Fontes, L; Pulido Fontes, M; Quesada Jiménez, P; Muruzabal Pérez, J; Mendioroz Iriarte, M

    2017-09-01

    Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B 12 . Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy

    Directory of Open Access Journals (Sweden)

    Laxmikant S Deshpande

    2014-01-01

    Full Text Available Status epilepticus (SE is a major clinical emergency that is associated with high mortality and morbidity. SE causes significant neuronal injury and survivors are at a greater risk of developing acquired epilepsy and other neurological morbidities, including depression and cognitive deficits. Benzodiazepines and some anticonvulsant agents are drugs of choice for initial SE management. Despite their effectiveness, over 40% of SE cases are refractory to the initial treatment with two or more medications. Thus there is an unmet need of developing newer anti-SE drugs. Levetiracetam (LEV is a widely prescribed anti-epileptic drug that has been reported to be used in SE cases, especially in benzodiazepine-resistant SE or where phenytoin cannot be used due to allergic side-effects. Levetiracetam’s non-classical antiepileptic mechanisms of action, favorable pharmacokinetic profile, general lack of central depressant effects and lower incidence of drug interactions contributes to its use in SE management. This review will focus on LEV’s unique mechanism of action that makes it a viable candidate for SE treatment.

  14. Epilepsy and psychosis: a practical approach.

    Science.gov (United States)

    Maguire, Melissa; Singh, Jasvinder; Marson, Anthony

    2018-04-01

    The psychoses of epilepsy can be classified according to their temporal relationship with seizures, namely as ictal, postictal and interictal psychosis. Interictal psychosis is the most common and may resemble schizophrenia. They can be challenging to diagnose and to manage, especially given the perception that some antipsychotic drugs may exacerbate seizures, while some antiepileptic medications may worsen psychosis. The current uncertainty around their best management means that some patients may not receive appropriate care. We propose a practical stepwise approach to managing psychosis in patients with epilepsy, summarising the key clinical features. We provide a framework for diagnosis, investigation and management of psychosis in the acute and long term. We also summarise the available evidence on the risk of psychosis with current antiepileptic drugs and the risk of seizures with antipsychotic drugs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

    Directory of Open Access Journals (Sweden)

    Olliaro P

    2004-01-01

    Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

  16. Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine, oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures in mice.

    Science.gov (United States)

    Luszczki, Jarogniew J; Wlaz, Aleksandra; Karwan, Slawomir; Florek-Luszczki, Magdalena; Czuczwar, Stanislaw J

    2013-11-15

    The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN - a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four second-generation antiepileptic drugs (lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), the step-through passive avoidance task (assessing long-term memory) and the grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by high-pressure liquid chromatography to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5mg/kg, i.p.) significantly enhanced the anticonvulsant action of lamotrigine (Poxcarbazepine in the maximal electroshock-induced tonic seizure test in mice. Furthermore, none of the investigated combinations of WIN with antiepileptic drugs were associated with any concurrent adverse effects with regards to motor performance, long-term memory or muscular strength. Pharmacokinetic characterization revealed that WIN had no impact on total brain concentrations of lamotrigine, oxcarbazepine, pregabalin and topiramate in mice. These preclinical data would suggest that WIN in combination with lamotrigine, pregabalin and topiramate is associated with beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced tonic seizure test. © 2013 Published by Elsevier B.V.

  17. Perampanel and Challenging Behaviour in Intellectual Disability and Epilepsy: A Management Dilemma

    Directory of Open Access Journals (Sweden)

    Emily Dolton

    2014-01-01

    Full Text Available We describe a case of a patient with a diagnosis of moderate learning disability with challenging behaviour and treatment refractory epilepsy. Antiepileptics can increase challenging behaviour; however, antipsychotics can provoke seizures. This results in a difficult balance for patient care. Due to worsening seizures, the patient was prescribed perampanel. This increased her aggression and agitation resulting in admission. We trialled four antipsychotic drugs to reduce her challenging behaviour, two of which worsened her seizures. It was necessary to continue antiepileptic medication to maintain adequate seizure control. However, the resulting uncontrolled challenging behaviour persisted, meaning she was unable to return to her family home on discharge. This case emphasises the difficult scenario clinician’s encounter when balancing the use of antipsychotics and antiepileptics. The case demonstrates the significant functional loss due to challenging behaviour, balanced against controlling life threatening seizures.

  18. DRUG MANAGEMENT REVIEWS IN DISTRICT DRUG MANAGEMENT UNIT AND GENERAL HOSPITAL

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2009-12-01

    Full Text Available Drug is one of the essential elements in healthcare that should be effectively and efficiently managed. Following thedecentralization in 2001 in Indonesia, drug management has changed in district drug management units and also in District General Hospitals. Certainly this condition influences the sustainability of drug access in primary health care such as in Community Health Center and District General Hospital, especially in drug financing policy. A cross sectional descriptive study to obtain information on drug management in public healthcare in district had been carried out between July and December 2006 in 10 District Public Drug Management Units from 10 district health offices and 9 district general hospitals as samples. Data were collected by interviewing heads of Drug Section in District Health Offices and heads of Hospital Pharmacies using structured questionnaires and observing drug storage in District Drug Management Units, Community Health Centers, and Hospital Pharmacies. Results of the study show that drug planning in District Health Offices and General Hospitals did not meet the basic real need in some districts nor District Hospitals. The minimum health service standards had no been achieved yet. Furthermore, drug procurement, storage and recording as well as reporting was not good enough either, such as shown by the existence of expired drugs. Lead time for drug delivery to community health centers in some districts was longer than the average of lead time in the past 3 years.

  19. Brand-name drug, generic drug, orphan drug. Pharmacological therapy with biosimilar drugs – provision of due diligence in the treatment process

    Science.gov (United States)

    Zajdel, Justyna

    2013-01-01

    Due diligence in the process of provision of healthcare services refers, among other elements, to the application of pharmacological therapy at a time which offers the greatest chance for a successful outcome of treatment, i.e. for achieving the optimum expected effect understood as an improvement in the patient's health, reduction of health risks or elimination of the disease. However, due diligence may also refer to actions aimed at ensuring that neither the patient nor the healthcare payer is required to incur unreasonable costs in the process of treatment. The validity of that statement stems not only from normative acts but also from ethical standards laid down in the Medical Code of Ethics (Article 57 section 2). It often happens that the provision of optimal treatment calls for deviations from the formal provisions included in Summary Product Characteristics (SPCs), and the application of drugs that are bioequivalent to reference drugs, which translates into a significant reduction of costs. The present study addresses the problem of acceptability of a specific form of drug substitution consisting in the replacement of a reference drug with a generic drug. Also explored are legal aspects associated with the possibility of therapy based on “off-label use”. The study reviews normative acts existing in the Polish and EU legislation. It also provides a clear definition of orphan drug, which has made it possible to make a distinction and investigate mutual relations between the concepts of brand-name (reference) drug, orphan drug and generic drug. PMID:24592133

  20. Sustainable medication: Microtechnology for personalizing drug treatment

    DEFF Research Database (Denmark)

    Faralli, Adele; Melander, Fredrik; Andresen, Thomas Lars

    2014-01-01

    drug dosing” using light-­‐polymerizable polymer hydrogels as carriers for free or nanoparticle-­‐encapsulated drugs. The total dose is simply controlled by the volume of drug-­‐loaded cross-­‐ linked hydrogel defined by patterned light from a standard projector (Fig. 1). The concept enables simple...

  1. Ohtahara Syndrome

    Science.gov (United States)

    ... are more often affected than girls. View Full Definition Treatment Antiepileptic drugs are used to control seizures, but are unfortunately ... Other therapies are symptomatic and supportive. × ... Definition Ohtahara syndrome is a neurological disorder characterized by ...

  2. GENERIC DRUG IN GLOBAL MARKET AND REGULATORY ENVIRONMENT

    OpenAIRE

    Pankaj Kumar*, Bharti Mangla2, Satbir Singh, Arapna Rana

    2017-01-01

    Different regulatory authorities regulate the drug development in various countries of the world. Various Regulatory authority for generic drug application Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceutical and Medical Devices Agency (PMDA), Health Product and Food Branch (HPFB) Central Drug Standard of Organization (CDSO). Generic manufacturers may file an abbreviated New Drug Application (ANDA) that incorporates the safety/effectiveness data submitted by ori...

  3. An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India.

    Science.gov (United States)

    Taur, Santosh R; Kulkarni, Namrata B; Gogtay, Nithya J; Thatte, Urmila M

    2013-04-01

    Therapeutic drug monitoring (TDM) is an important adjunct to the treatment of epilepsy. However, few studies have actually correlated plasma levels of antiepileptic drugs (AEDs) with treatment response. The present audit aimed to study (i) the association between seizure control and number of AEDs, plasma AED concentration, and concomitant use of antitubercular drugs; (ii) the pattern of indications for TDM requisitions; and (iii) the association between referral for toxicity and plasma AED concentration. This observational and retrospective study was carried out to analyze the TDM data of patients referred between January 2008 and December 2011. As per the International League Against Epilepsy Task Force 2009, patients were categorized into responders and nonresponders. Plasma AED levels were interpreted as below, within, and above the reference range. Of 3206 TDM requisitions, 67% were monotherapy and 33% were 2 or more AEDs. Only 8% were responders as against 92% nonresponders. Of 95 patients on concomitant antituberculosis treatment, 72 were nonresponders, with odds ratio (95% confidence interval) 3.71 [2.19 to 6.23]. Breakthrough seizure (37%) was the most common indication followed by suspected toxicity and routine monitoring in 22% each and suspected nonadherence in 11% of the total requests. In 52% of patients, plasma levels were below the reference range, and they were equally distributed amongst responders and nonresponders. Among patients referred for suspected phenytoin toxicity, only 59% (50.6 to 67.8) had plasma concentrations above the reference range. TDM continues to remain an important tool to support dose individualization when the patient is receiving multiple AEDs or other drugs such as antitubercular medicines, to assess compliance, and to monitor and treat toxicity.

  4. Development, use and evaluation of drugs

    DEFF Research Database (Denmark)

    Hansen, E H; Launsø, Laila

    1987-01-01

    . Drugs offer a standard solution to health problems independent of the individuals' social life. Thus drugs become a tool which function in agreement with the disintegrated and achievement-orientated approach to disease as it is organized today. In general the statements in this article are not limited...

  5. 21 CFR 120.6 - Sanitation standard operating procedures.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Sanitation standard operating procedures. 120.6... Provisions § 120.6 Sanitation standard operating procedures. (a) Sanitation controls. Each processor shall have and implement a sanitation standard operating procedure (SSOP) that addresses sanitation...

  6. Stability-indicating liquid chromatographic method for quantification of new anti-epileptic drug lacosamide in bulk and pharmaceutical formulation

    Directory of Open Access Journals (Sweden)

    Chhalotiya Usmangani K.

    2012-01-01

    Full Text Available An isocratic stability indicating reversed-phase liquid chromatographic determination was developed for the quantitative determination of lacosamide in the pharmaceutical dosage form. A Hypersil C-18, 4.5μm column with mobile phase containing acetonitrile-water (20:80, v/v was used. The flow rate was 1.0 mL min-1 and effluents were monitored at 258 nm. The retention time of lacosamide was 8.9 min. The method was found to be linear in the concentration range of 5-100 μg/ml and the recovery was found to be in the range of 99.15 - 100.09 %. The limit of detection and limit of quantification were found to be 2 μg/ml and 5 μg/ml, respectively. Lacosamide stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and dry heat degradation. The drug was found to be stable to the dry heat and acidic condition attempted. The proposed method was validated and successfully applied to the estimation of lacosamide in tablet dosage forms.

  7. Observational study of drug-drug interactions in oncological inpatients

    Directory of Open Access Journals (Sweden)

    María Sacramento Díaz-Carrasco

    2018-01-01

    Full Text Available Objective: To determine the prevalence of potential clinically relevant drug- drug interactions in adult oncological inpatients, as well as to describe the most frequent interactions. A standard database was used. Method: An observational, transversal, and descriptive study including patients admitted to the Oncology Service of a reference hospital. All prescriptions were collected twice a week during a month. They were analysed using Lexicomp® database, recording all interactions classified with a level of risk: C, D or X. Results: A total of 1 850 drug-drug interactions were detected in 218 treatments. The prevalence of treatments with at least one clinically relevant interaction was 95%, being 94.5% for those at level C and 26.1% for levels D and X. The drugs most commonly involved in the interactions detected were opioid analgesics, antipsychotics (butyrophenones, benzodiazepines, pyrazolones, glucocorticoids and heparins, whereas interactions with antineoplastics were minimal, highlighting those related to paclitaxel and between metamizole and various antineoplastics. Conclusions: The prevalence of clinically relevant drug-drug interactions rate was very high, highlighting the high risk percentage of them related to level of risk X. Due to the frequency of onset and potential severity, highlighted the concomitant use of central nervous system depressants drugs with risk of respiratory depression, the risk of onset of anticholinergic symptoms when combining morphine or haloperidol with butylscopolamine, ipratropium bromide or dexchlorpheniramine and the multiple interactions involving metamizole.

  8. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    Science.gov (United States)

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels

    DEFF Research Database (Denmark)

    Kim, Robin Y; Pless, Stephan A; Kurata, Harley T

    2017-01-01

    Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation. To elucid......Retigabine (RTG) is a first-in-class antiepileptic drug that suppresses neuronal excitability through the activation of voltage-gated KCNQ2-5 potassium channels. Retigabine binds to the pore-forming domain, causing a hyperpolarizing shift in the voltage dependence of channel activation....... These findings reveal an important role for PIP2 in coupling retigabine binding to altered VSD function. We identify a polybasic motif in the proximal C terminus of retigabine-sensitive KCNQ channels that contributes to VSD-pore coupling via PIP2, and thereby influences the unique gating effects of retigabine....

  10. [Nootropics and antioxidants in the complex therapy of symptomatic posttraumatic epilepsy].

    Science.gov (United States)

    Savenkov, A A; Badalian, O L; Avakian, G N

    2013-01-01

    To study the possibility of application of nootropics and antioxidants in the complex antiepileptic therapy, we examined 75 patients with symptomatic focal posttraumatic epilepsy. A statistically significant reduction in the number of epileptic seizures, improvement of cognitive function and quality of life of the patients as well as a decrease in the severity of depression and epileptic changes in the EEG were identified. The potentiation of antiepileptic activity of basic drugs, normalization of brain's electrical activity and reduction in EEG epileptiform activity, in particular coherent indicators of slow-wave activity, were noted after treatment with the antioxidant mexidol. A trend towards the improvement of neuropsychological performance and quality of life was observed. There was a lack of seizure aggravation typical of many nootropic drugs. Thus, phenotropil and mexidol can be recommended for complex treatment of symptomatic posttraumatic epilepsy.

  11. [A modified approach to the diagnosis and therapy of epileptic seizures in the third stage of life].

    Science.gov (United States)

    Gavranović, Muhamed; Delilović, Jasminka; Kurtović, Azra; Alibegović, Sakib; Rajić, Zeljka; Ajanović, Zakira

    2003-01-01

    Incidence of seizures in the elderly is nowadays greater than the one characteristic for children up to 10 years of age. Epileptic seizures are the third most common serious neurological disorder in this age group, after stroke and dementia. Optimal care for those patients, regarding to the seizures, demands some modification in diagnostic and treatment approach. Aim of this report was to point out problems in diagnostics, treatment and most common mistakes in practice. Fifty one patients were assessed, aged 65-83 years, (30 female and 21 male), with diagnosis of epilepsy and established antiepileptic treatment. All patients were re-examined, and following procedures were utilised: auto and heteroanamnesis (especially data provided by eyewitnesses), clinical examination, biochemical status, complete cardiological examination, EEG registration, serum concentrations of antiepileptic drugs, CT and MRI scan. Out of 51 patients 11 were misdiagnosed (syncope, provoked seizures, TIA). The most common form of seizures were partial seizures with or without secondary generalization (31 cases). Etiologic factors: stroke (25 cases), arteriosclerosis (7 cases), tumours (3 cases), trauma (2 cases), unknown (3 cases) cardiovascular diseases (29 casec) diabetes mellitus (20 cases), respiratory disturbance (12 cases) renal disturbances (8 cases). Only 30 patients had monotherapy from the beginning, with either carbamazepine or valproate. Rest were treated from the beginning with 2 antiepileptic drugs (phenobarbital + carbamazepine or pheytoin + phenobarbital). Adverse effects were recorded in 21 patients. I. It is crucial to distingiush unprovoked and provoked seizures during diagnostic procedures, as well as epileptic and non-epileptic attacks; 2. Principle of monotherapy is conditio sine qua non, and in treatment attention should be paid to co-morbidity, multitherapy, drug interactions, intoxication, diminished detoxication and elimination of drugs, as well as increased

  12. Multiple treatment comparisons in epilepsy monotherapy trials

    Directory of Open Access Journals (Sweden)

    Chadwick David W

    2007-11-01

    Full Text Available Abstract Background The choice of antiepileptic drug for an individual should be based upon the highest quality evidence regarding potential benefits and harms of the available treatments. Systematic reviews and meta-analysis of randomised controlled trials should be a major source of evidence supporting this decision making process. We summarise all available individual patient data evidence from randomised controlled trials that compared at least two out of eight antiepileptic drugs given as monotherapy. Methods Multiple treatment comparisons from epilepsy monotherapy trials were synthesized in a single stratified Cox regression model adjusted for treatment by epilepsy type interactions and making use of direct and indirect evidence. Primary outcomes were time to treatment failure and time to 12 month remission from seizures. A secondary outcome was time to first seizure. Results Individual patient data for 6418 patients from 20 randomised trials comparing eight antiepileptic drugs were synthesized. For partial onset seizures (4628 (72% patients, lamotrigine, carbamazepine and oxcarbazepine provide the best combination of seizure control and treatment failure. Lamotrigine is clinically superior to all other drugs for treatment failure but estimates suggest a disadvantage compared to carbamazepine for time to 12 month remission [Hazard Ratio (95% Confidence Interval = 0.87(0.73 to 1.04] and time to first seizure [1.29(1.13 to 1.48]. Phenobarbitone may delay time to first seizure [0.77(0.61 to 0.96] but at the expense of increased treatment failure [1.60(1.22 to 2.10]. For generalized onset tonic clonic seizures (1790 (28% patients estimates suggest valproate or phenytoin may provide the best combination of seizure control and treatment failure but some uncertainty remains about the relative effectiveness of other drugs. Conclusion For patients with partial onset seizures, results favour carbamazepine, oxcarbazepine and lamotrigine. For

  13. 21 CFR 130.8 - Conformity to definitions and standards of identity.

    Science.gov (United States)

    2010-04-01

    ... identity. 130.8 Section 130.8 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Conformity to definitions and standards of identity. In the following conditions, among others, a food does not conform to the definition and standard of identity therefor: (a) If it contains an ingredient for...

  14. Fractional laser-assisted drug delivery

    DEFF Research Database (Denmark)

    Erlendsson, Andrés M; Doukas, Apostolos G; Farinelli, William A

    2016-01-01

    BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging......, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous...

  15. Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

    Science.gov (United States)

    Sanz-García, Ancor; Vega-Zelaya, Lorena; Pastor, Jesús; Torres, Cristina V.; Sola, Rafael G.; Ortega, Guillermo J.

    2016-01-01

    Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area. PMID:28060326

  16. Fertility rate oF epileptic women at Kenyatta national Hospital

    African Journals Online (AJOL)

    2008-07-07

    Jul 7, 2008 ... multifaceted, and both epilepsy and antiepileptic drug (aeDs) use may alter fertility and pregnancy ... Conclusion: Fertility rate in epileptic women is decreased by two thirds ..... The effect of this bias on our primary aim was.

  17. Mobile phones and seizures: drug-resistant epilepsy is less common in mobile-phone-using patients.

    Science.gov (United States)

    Nagarjunakonda, Sundarachary; Amalakanti, Sridhar; Uppala, Veeramma; Gajula, Rama Krishna; Tata, Ramya Sree; Bolla, Hima Bindu; Rajanala, Lalitha; Athina, Srinivasulu; Daggumati, Rajeswari; Lavu, Harish; Devanaboina, Anil Kumar

    2017-01-01

    Epilepsy is a condition where patients have seizures due to abnormal nerve impulses in the brain. The effect of mobile phone radiation on patients with seizures is not known. To compare the seizure profile of patients not using mobile phones with that of their peers using mobile phones. In a retrospective cohort study performed at the neurology outpatient department of Guntur Medical College Hospital, Guntur, India from September 2014 to September 2015, we included 178 consecutive epileptic patients aged 16-65 years, who had had seizure disorder for 1 year or more. On the basis of their possession and usage of mobile phones, patients were divided into three groups: no mobile group (NMG), home mobile group (HMG) and personal mobile group (PMG). We obtained data on seizure frequency and recorded details of mobile phone usage and their antiepileptic drug (AED) treatment. 107 NMG, 3 HMG and 68 PMG patients were finalised for the analysis. There was no significant difference in the number of seizures in the past year between the three groups. The PMG (3.7%) contained a clinically significant lower proportion of patients with drug-resistant epilepsy than the NMG (28.2%). Patients with drug-responsive epilepsy were 7.4 (95% CI 1.4 to 39.9) (p=0.01) times more likely to be found in the PMG than in the NMG after adjustment for differences in sex and occupation. Although the experimental data remain inconclusive, our clinical study suggests that patients who use mobile phones are less likely to have drug-resistant epilepsy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. Health-related quality of life in epilepsy patients receiving anti-epileptic drugs at National Referral Hospitals in Uganda: a cross-sectional study.

    Science.gov (United States)

    Nabukenya, Anne M; Matovu, Joseph K B; Wabwire-Mangen, Fred; Wanyenze, Rhoda K; Makumbi, Fredrick

    2014-04-12

    Epilepsy is a devastating disorder that impacts on patients' quality of life, irrespective of use of anti epileptic drugs (AEDs). This study estimates the health-related quality of life (HRQOL) and its associated predictors among epilepsy patients receiving AEDs. A total of 175 epilepsy patients already receiving AED for at least 3 months were randomly selected and interviewed from mental clinics at Mulago and Butabika national referral hospitals in Uganda between May - July 2011. A HRQOL index, the primary outcome, was constructed using items from Quality Of Life in Epilepsy Inventory (QOLIE-31) and the Hospital Anxiety and Depression Scale (HADS) questionnaires. The internal consistency and adequacy of these items was also computed using Cronbach's alpha and Kaiser-Meyer-Olkin tests. Partial correlations were used to evaluate the contribution of the health dimensions (mental, psychological, social, physical functioning and emotional well being) and, multiple linear regressions to determine factors independently associated with HRQOL. Just about half of the respondents (54%) were males, and nearly two thirds (62%) had received AEDs for at least 12 months. The average age was 26.6 years (SD = 11.1). The overall HRQOL mean score was 58 (SD = 13) on a scale of 0-100. The average scores of different dimensions or subscales ranged from 41 (physical) to 65 (psychological). At least three quarters (75%) of all subscales had good internal consistency and adequacy. The largest variations in the overall HRQOL were explained by social and mental functioning; each accounting for about 30% of the difference in the HRQOL but seizure control features explained a little (6%) variation. Factors negatively associated with HRQOL were poly-therapy (-1.16, p = 0.01) and frequency of seizures (-2.29, p = 0.00). Other factors associated with overall HRQOL included drug side effects, sex, marital status and education. Duration on AEDs was not a significant predictor of HRQOL. The HRQOL

  19. Patterns of antiepileptic drug use and seizure control among people ...

    African Journals Online (AJOL)

    Background Epilepsy is characterized by episodic and unpredictable seizure recurrences which are often amenable to medical treatment. Simple and readily available medications can be used to control seizures in epilepsy. However, in many communities in developing countries seizure control among people living with ...

  20. Drug: D09140 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ... Same as: E00207 Therapeutic category: 5100 ... Caprifoliaceae (honeysuckle family) Lonicera japonica flower bud; Standards for non-pharmacopoeial crude drugs ... PubChem: 96025820 ...