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Sample records for antiepileptic drugs compelling

  1. Antiepileptic drugs in neuroprotection

    Czech Academy of Sciences Publication Activity Database

    Pitkanen, A.; Kubová, Hana

    2004-01-01

    Roč. 5, č. 4 (2004), s. 777-798 ISSN 1465-6566 R&D Projects: GA MZd NF6474 Institutional research plan: CEZ:AV0Z5011922 Keywords : antiepileptic drugs * anticonvulsant * epilepsy Subject RIV: FH - Neurology

  2. Antiepileptic drugs and intrauterine death

    DEFF Research Database (Denmark)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio

    2015-01-01

    OBJECTIVE: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). METHODS: The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs...

  3. Antiepileptic drugs and intrauterine death

    NARCIS (Netherlands)

    Tomson, Torbjörn; Battino, Dina; Bonizzoni, Erminio; Craig, John J.; Lindhout, Dick; Perucca, Emilio; Sabers, Anne; Thomas, Sanjeev V.; Vajda, Frank

    2015-01-01

    Objective: To compare the risk of spontaneous abortions and stillbirth associated with maternal use of different antiepileptic drugs (AEDs). Methods: The EURAP registry is an observational international cohort study primarily designed to determine the risk of major congenital malformations (MCMs)

  4. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    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. 

  5. Antiepileptic drugs in Rett Syndrome.

    Science.gov (United States)

    Pintaudi, Maria; Calevo, Maria Grazia; Vignoli, Aglaia; Baglietto, Maria Giuseppina; Hayek, Yussef; Traverso, Maria; Giacomini, Thea; Giordano, Lucio; Renieri, Alessandra; Russo, Silvia; Canevini, MariaPaola; Veneselli, Edvige

    2015-07-01

    We investigated drugs most often used to treat epilepsy in Rett Syndrome and their efficacy in a large cohort of Italian patients. This is a multi-centre retrospective study. Data of 165 Rett subjects were collected from the patients' files, and hospital charts. The efficacy of antiepileptic drugs (AEDs) was classified as follows: not effective; decrease in seizure frequency ≥50% for at least 6 months; seizure-free for at least 2 years. Phenotypic and genetic categorization of patients was performed and it was considered in AEDs efficacy evaluation. There were 130 epileptic patients.Sodium valproate (VPA) was the most commonly administered AED (44.3%) at seizure onset, followed by Carbamazepine (CBZ) (25.4%) and Phenobarbital (PB) (13%). Monotherapy was the first treatment option in most patients. VPA and CBZ proved to be equally effective in Rett patients who presented seizures within the typical age range (4-5 years), while Lamotrigine (LTG) was effective for patients in whom epilepsy started later. Overall, the frequency of side effects was low and the most often observed ones were restlessness and somnolence. Our study suggests that LTG, VPA and CBZ can be used as drugs of first choice in Rett Syndrome. The association of four drugs should be avoided since it did not result in any significant clinical improvement. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. New antiepileptic drugs and preparations.

    Science.gov (United States)

    Yoon, Y; Jagoda, A

    2000-11-01

    Epilepsy affects 1.2% to 4.4% of the general population. Given the clinical profile of the newer antiepileptic agents, it is likely their usage will increase in the coming years, thus increasing the emergency physician's exposure to these medications and their side effects. Several of these side effects can have high morbidity, such as the aplastic anemia and hepatotoxicity caused by felbamate, and the Stevens-Johnson syndrome associated with lamotrigine. Overdoses of these medications also could increase, as will our knowledge of recognizing and managing them. The clinical spectrum of the newer medications is the treatment of partial seizures. None of the newer medications can be orally loaded nor are they available in an i.v. preparation. Serum drug levels are not available in most institutions and are not routinely measured in the ED. The new preparations of phenytoin, diazepam, and valporic acid add increased efficiency in drug administration, providing a new method for prehospital treatment of seizures and a more tolerable means of administration in the ED.

  7. 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...

  8. Interactions between antiepileptic drugs and herbal medicines

    OpenAIRE

    Landmark, C. J.; Patsalos, P. N.

    2008-01-01

    As a therapeutic class, antiepileptic drugs (AEDs) have a high propensity to interact and many interactions with concomitant medications have been described. Increasingly, herbal medicines are often used by patients with epilepsy and the risk that these may interact with their AED medication is now being realised. The purpose of this review is to highlight the interactions that have been reported between AEDs and herbal medicines. Overall, the published data are sparse and comprise of both ph...

  9. 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...

  10. 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....

  11. 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...

  12. Antiepileptic Drug Nonadherence and Its Predictors among People with Epilepsy

    OpenAIRE

    Getnet, Asmamaw; Woldeyohannes, Solomon Meseret; Bekana, Lulu; Mekonen, Tesfa; Fekadu, Wubalem; Menberu, Melak; Yimer, Solomon; Assaye, Adisu; Belete, Amsalu; Belete, Habte

    2016-01-01

    Introduction. Antiepileptic drugs are effective in the treatment of epilepsy to the extent that about 70% of people with epilepsy can be seizure-free, but poor adherence to medication is major problem to sustained remission and functional restoration. The aim of this study was to assess the prevalence and associated factors of antiepileptic drug nonadherence. Methods. Cross-sectional study was conducted on 450 individuals who were selected by systematic random sampling method. Antiepileptic d...

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

    Science.gov (United States)

    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.

  14. Patterns of antiepileptic drug use and seizure control among people ...

    African Journals Online (AJOL)

    Method We assessed the patterns of antiepileptic drug use and seizure control among persons living with epilepsy in a suburban community in Southeast Nigeria found in a two phase cross-sectional study. Detailed information on epilepsy treatment, seizure control and patterns of antiepileptic drug use (AED) by those ...

  15. Drug utilisation study in patients receiving antiepileptic drugs in Colombia.

    Science.gov (United States)

    Machado-Alba, J E; Calvo-Torres, L F; García-Betancur, S; Aguirre-Novoa, A; Bañol-Giraldo, A M

    2016-03-01

    This study examines the indications according to which antiepileptic drugs are prescribed and used in a population of patients enrolled in the Colombian national health system (SGSSS). Retrospective cross-sectional study. From the pool of individuals in 34 Colombian cities who used antiepileptic drugs between 18 July, 2013 and 31 August, 2014 during a period of no less than 12 months, we obtained a random sample stratified by city. Socio-demographic, pharmacological and comorbidity variables were analysed. Continuous and categorical variables were compared, and logistic regression models were used. Our patient total was 373 patients, with 197 women (52.1%) and a mean age of 41.9 ± 21.7 years; 65.4% of the patients were treated with monotherapy. The most frequently used drugs were valproic acid (53.1%) and carbamazepine (33.2%). Epilepsy was the most frequent indication (n=178; 47.7%); however, 52.3% of the patients were prescribed antiepileptics for different indications, especially neuropathic pain (26.8%), affective disorders (14.2%) and migraine prophylaxis (12.3%). A total of 81 patients with epilepsy (46.6%) displayed good seizure control while another 25 (14.4%) had drug-resistant epilepsy. In the multivariate analysis, medication adherence was associated with a lower risk of treatment failure in patients with epilepsy (OR: 0.27; 95%CI, 0.11-0.67). In Colombia, antiepileptic drugs are being used for indications other than those originally intended. Monotherapy is the most commonly used treatment approach, together with the use of classic antiepileptic drugs. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  16. 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

  17. Pharmacogenetics of adverse reactions to antiepileptic drugs.

    Science.gov (United States)

    Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M

    2018-04-01

    Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Antiepileptic drug therapy the story so far.

    Science.gov (United States)

    Brodie, Martin J

    2010-12-01

    The story began on 11th May 1857 when Charles Locock commented in the Lancet on his use of potassium bromide in 15 cases of "hysterical" epilepsy in young women. The next development was the serendipitous discovery of the anticonvulsant properties of phenobarbital by Alfred Hauptmann in 1912. This predated by more than 20 years the screening of potential therapeutic agents against "electrical seizures" in cats by Houston Merritt and Tracy Putnam. The result was the launching of phenytoin in 1938. Next came primidone, ethosuximide, carbamazepine and valproic acid, all of which can be regarded as first generation antiepileptic drugs (AEDs). Shortly after their synthesis, the benzodiazepines were rapidly recognised as having anticonvulsant activity. The modern era focused on the systematic screening of many thousands of compounds against rodent seizure models under the Anticonvulsant Drug Development Program in the US. This resulted in the global licensing, in chronological order, of vigabatrin, zonisamide, oxcarbazepine, lamotrigine, felbamate, gabapentin, topiramate, tiagabine, levetiracetam, pregabalin and lacosamide. Rufinamide is available in the US and Europe for Lennox-Gastaut syndrome and stiripentol has been made available for Dravet syndrome under the European orphan drug scheme. Eslicarbazepine can be prescribed in Europe for partial seizures, but not in the US. Has all this activity improved the lives of people with epilepsy? The short answer is-probably yes, but not by very much! This paper will conclude with a précis of the views of a selected group of paediatric and adult epileptologists on the advances in pharmacological management achieved over the last 20 years. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. Availability of antiepileptic drugs across Europe.

    Science.gov (United States)

    Baftiu, Arton; Johannessen Landmark, Cecilie; Nikaj, Valent; Neslein, Inger-Lise; Johannessen, Svein I; Perucca, Emilio

    2015-12-01

    Europe consists of 53 countries with widely different economic conditions and different political, educational, and health care systems. This study was aimed at determining the availability of antiepileptic drugs (AEDs) across Europe. An electronic questionnaire was submitted to all 43 European chapters of the International League Against Epilepsy (ILAE). Outcome measures were availability of older, newer, and newest AEDs, generic products, indications, reimbursement rules, and reasons for lack of availability of AEDs. Countries were divided according to economic status as defined by the World Bank. Thirty-four chapters (79%) provided data. There were large differences in AED availability across countries, especially between high-income countries and the other countries. The newest AEDs were not available in any of the 12 non-high-income countries. Availability was higher in countries with public reimbursement systems. Reimbursement policies ranged from full reimbursement for all AEDs to complete lack of reimbursement. Main hurdles for poor access to AEDs included lack of regulatory approval, high prices and reimbursement restrictions. The availability of AEDs differs across European countries, with many hurdles hampering access to epilepsy medicines, particularly to new medications. These findings raise major concerns on the quality of epilepsy care in many countries. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  20. Levels of Antiepileptic Drugs and the Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  3. [Combined treatment with antiepileptic drugs. Andalusian Epilepsy Guide 2015].

    Science.gov (United States)

    Sánchez-Álvarez, Juan C; Ramos-Lizana, Julio; Machado-Casas, Irene S; Serrano-Castro, Pedro J; Martínez-Antón, Jacinto L; Ruiz-Giménez, Jesús

    2015-04-16

    The aim of this study was to draw up a set of recommendations based on scientific evidence and in agreement with authors and reviewers, which address fundamental issues concerning the combination of antiepileptic drugs. A committee of 11 experts belonging to the Sociedad Andaluza de Epilepsia (SAdE--Andalusian Epilepsy Society), of whom seven were neurologists, three were neuropaediatricians and one was a neurologist-neurophysiologist, all of them with long experience in epilepsy, promoted a comprehensive literature review among 55 experts in epilepsy who were members of the SAdE, with the aim of searching for any evidence that might be available on diagnostic or therapeutic matters in epilepsy. The guidelines were set out in 35 chapters. One of the chapters addressed the combination of antiepileptic drugs in the treatment of epilepsy. Taking 77 bibliographical references and the consensus view of authors and reviewers as their starting point, a set of easily applicable recommendations were drawn up. Combining antiepileptic drugs in patients with epilepsy whose seizures are not controlled with a single drug can, on many occasions, result in their going back into remission. There are a series of factors related with the type of epilepsy and characteristics of the patient and with the antiepileptic drugs to be used in combination that may favour a successful therapeutic outcome. Over-treatment with the combination of antiepileptic drugs must be avoided as far as possible. The results of this review provide a set of recommendations regarding combined treatment with antiepileptic drugs, based on scientific evidence and the agreement of authors, that are simple, useful and easy to apply at the different levels of healthcare.

  4. 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

    Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex...... is the enzyme system that converts androgens to estrogens and consequently an inhibition may induce a hormone imbalance. Twelve antiepileptic drugs, used in mono or polytherapy for the treatment of children, were tested for their ability to inhibit aromatase (CYP19) with commercially available microsomes from...

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

    DEFF Research Database (Denmark)

    Olesen, Jonas Bjerring; 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...

  6. Antiepileptic Drug Nonadherence and Its Predictors among People with Epilepsy.

    Science.gov (United States)

    Getnet, Asmamaw; Woldeyohannes, Solomon Meseret; Bekana, Lulu; Mekonen, Tesfa; Fekadu, Wubalem; Menberu, Melak; Yimer, Solomon; Assaye, Adisu; Belete, Amsalu; Belete, Habte

    2016-01-01

    Introduction. Antiepileptic drugs are effective in the treatment of epilepsy to the extent that about 70% of people with epilepsy can be seizure-free, but poor adherence to medication is major problem to sustained remission and functional restoration. The aim of this study was to assess the prevalence and associated factors of antiepileptic drug nonadherence. Methods. Cross-sectional study was conducted on 450 individuals who were selected by systematic random sampling method. Antiepileptic drug nonadherence was measured by Morisky Medication Adherence Scale (MMAS) and logistic regression was used to look for significant associations. Result. The prevalence of AEDs nonadherence was 37.8%. Being on treatment for 6 years and above [AOR = 3.47, 95% CI: 1.88, 6.40], payment for AEDs [AOR = 2.76, 95% CI: 1.73, 4.42], lack of health information [AOR = 2.20, 95% CI: 1.41,3.43], poor social support [AOR = 1.88, 95%, CI: 1.01, 3.50], perceived stigma [AOR = 2.27, 95% CI: 1.45, 3.56], and experience side effect [AOR = 1.70, 95% CI: 1.06, 2.72] were significantly associated with antiepileptic drug nonadherence. Conclusion. More than one-third of people with epilepsy were not compliant with their AEDs. Giving health information about epilepsy and its management and consequent reduction in stigma will help for medication adherence.

  7. Antiepileptic Drug Nonadherence and Its Predictors among People with Epilepsy

    Directory of Open Access Journals (Sweden)

    Asmamaw Getnet

    2016-01-01

    Full Text Available Introduction. Antiepileptic drugs are effective in the treatment of epilepsy to the extent that about 70% of people with epilepsy can be seizure-free, but poor adherence to medication is major problem to sustained remission and functional restoration. The aim of this study was to assess the prevalence and associated factors of antiepileptic drug nonadherence. Methods. Cross-sectional study was conducted on 450 individuals who were selected by systematic random sampling method. Antiepileptic drug nonadherence was measured by Morisky Medication Adherence Scale (MMAS and logistic regression was used to look for significant associations. Result. The prevalence of AEDs nonadherence was 37.8%. Being on treatment for 6 years and above [AOR = 3.47, 95% CI: 1.88, 6.40], payment for AEDs [AOR = 2.76, 95% CI: 1.73, 4.42], lack of health information [AOR = 2.20, 95% CI: 1.41,3.43], poor social support [AOR = 1.88, 95%, CI: 1.01, 3.50], perceived stigma [AOR = 2.27, 95% CI: 1.45, 3.56], and experience side effect [AOR = 1.70, 95% CI: 1.06, 2.72] were significantly associated with antiepileptic drug nonadherence. Conclusion. More than one-third of people with epilepsy were not compliant with their AEDs. Giving health information about epilepsy and its management and consequent reduction in stigma will help for medication adherence.

  8. Antiepileptic Drugs and Bone Health in Thai Children with Epilepsy.

    Science.gov (United States)

    Paticheep, Sudathip; Chotipanich, Chanisa; Khusiwilai, Khanittha; Wichaporn, Anuttara; Khongsaengdao, Subsai

    2015-06-01

    Background: Epilepsy is the most common neurological disease in children. The patient must take antiepileptic drug for controlling the seizure at least 2 years. Many previous studies show the effect of antiepileptic drug to vitamin D status and bone health. To study the prevalence of vitamin D deficiency and bone mineral density in the children who are taking antiepileptic drug at least 6 months. Thirty epileptic children who are 3-18 years old with taking antiepileptic drug at least 6 months and 30 healthy children in the same age were performed to investigate serum 25-hydroxyvitamin D, calcium, phosphorus, magnesium, creatinine, alkaline phosphatase, albumin, parathyroid hormone, spot urine calcium, spot urine phosphorus, spot urine creatinine and bone mineral density between October 2012 to September 2013. Seven epileptic children (23.3%), eight healthy children (26.7%) have vitamin D deficiency. Only 3 epileptic children who are cerebral palsy also have low bone mineral density. There is only statistical significant of decreased serum albumin (p-value = 0.03) and corrected serum calcium (p-value = 0.04) that reveal in epileptic children group. Evaluation of serum 25-hydroxyvitamin D status and bone metabolism is essential in the treatment of childhood epilepsy.

  9. Co-prescription of antiepileptic drugs and contraceptives

    NARCIS (Netherlands)

    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

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

    Science.gov (United States)

    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.

  11. Economic evaluation of anti-epileptic drug therapies with specific focus on teratogenic outcomes

    NARCIS (Netherlands)

    Jentink, J.; Boersma, C.; de Jong-van den Berg, L.T.; Postma, M.J.

    2012-01-01

    BACKGROUND: Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy. Objectives: To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to

  12. [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.

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

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    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.

  14. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development.

    Science.gov (United States)

    Forcelli, Patrick A; Janssen, Megan J; Vicini, Stefano; Gale, Karen

    2012-09-01

    Drug exposure during critical periods of brain development may adversely affect nervous system function, posing a challenge for treating infants. This is of particular concern for treating neonatal seizures, as early life exposure to drugs such as phenobarbital is associated with adverse neurological outcomes in patients and induction of neuronal apoptosis in animal models. The functional significance of the preclinical neurotoxicity has been questioned due to the absence of evidence for functional impairment associated with drug-induced developmental apoptosis. We used patch-clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal learning at weaning. Recordings from control animals revealed increased inhibitory and excitatory synaptic connectivity between postnatal day (P)10 and P18. This maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital exposure impaired striatal-mediated behavior on P25. Neuroprotective pretreatment with melatonin, which prevents drug-induced neurodevelopmental apoptosis, prevented the drug-induced disruption in maturation. Levetiracetam was found not to disrupt synaptic development. Our results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult. These findings suggest a mechanism by which early life exposure to antiepileptic drugs can impact cognitive and behavioral outcomes, underscoring the need to identify therapies that control seizures without compromising synaptic maturation. Copyright © 2012 American Neurological Association.

  15. Cognitive functions, epileptic syndromes and antiepileptic drugs

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    Paulo R. M. Bittencourt

    1992-03-01

    Full Text Available Cognitive function of patients on monotherapy specific for their epileptic syndrome has been studied infrequently. We evaluated 7 patients with symptomatic localised epilepsies (SEL on phenytoin aged 30±12 (mean±standard deviation years, 8 with idiopathic generalised epilepsies on sodium valproate aged 18±4 years, 16 with SEL on carbamazepine aged 28±11 years, and 35 healthy controls aged 27±11 years. All subjects were of normal intelligence, educated appropriately to age, and led productive lives in the community. Two of the patients on carbamazepine and one on valproate had less than five partial, absence or myoclonic seizures monthly, the remaining were controlled. Carbamazepine serum concentrations were 12±5 ug/ml, phenytoin were 23±7, and valproate were 62±23 (mean±sd. Tests included immediate recall and recognition for pictures, Stroop test, delayed recall and recognition of pictures. Patients on phenytoin and valproate performed significantly worse than controls on immediate recall, and patients on carbamazepine performed significantly worse than controls in Stroop test (p<0,01. The results indicate relatively minor effects of the epileptic syndromes and of phenytoin, carbamazepine and valproate on cognition of patients with controlled epilepsy leading productive lives in the community. We conclude that the cognitive deficit found in chronic epileptic patients on polytherapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningul results.

  16. The Influence of Antiepileptic Drugs on Thyroid Hormon Levels

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    İsmail Apak

    2006-01-01

    Full Text Available Fourty epileptic patients who were followed at Neurology Department of Diyarbakır Dicle University Medical School and taking antiepileptic drugs for at least a year, were included in the study. Twenty of patients (50% were male and 20 (50% were female. Patients were divided into 3 groups according to drugs they were treated with. The age range of 14 patients using valproate were between 15 and 44 years (mean 27.7 and they were taking the medication for 1 to 4 years (mean 2.67 years. Ages of 11 patients taking phenytoin were between 18 and 41 years (mean 28.7. Fifteen patients taking carbamazepine were between 16 and 43 years of age (mean 28.5 and duration of their therapy were 1 to 3 years (mean 2.6. The aim of this study was to search the effects of antiepileptic drugs on thyroid hormone levels in epileptic patients. Levels of T4, FT4, T3, FT3 and TSH were analyzed and following results were obtained. In group of patients receiving valproate, T4 levels decreased significantly. No change has been detected at FT4, T3.FT3 and TSH levels. T4 and FT4 levels decreased significantly at the patients using phenytoin. No change has been observed at T3, FT3 and TSH levels. There were no significant changes at T3, FT3 and TSH levels in the group of patients taking carbamazepine, however T4 and FT4 levels decreased significantly. The decrease at T4 levels were greater at carbamazepine, valproat and phenytoin, respectively. The most prominent decrease of FT4 levels were at the group taking phenytoin while the group treated with valproate were effected the least. The results of this study has shown that antiepileptic drugs affect thyroid functions, and patients using these drugs should be regularly followed up for any possible thyroid dysfunction.

  17. 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

  18. Teratogenic potential of antiepileptic drugs in the zebrafish model.

    Science.gov (United States)

    Lee, Sung Hak; Kang, Jung Won; Lin, Tao; Lee, Jae Eun; Jin, Dong Il

    2013-01-01

    The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ), ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM), levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf)) to termination of hatching (72 hpf) which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI) of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.

  19. 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

  20. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-01-01

    The /sup 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 /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 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 /sup 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, /sup 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 /sup 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 /sup 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 /sup 13/C breath test data will transport very different informations about enzyme induction in these neonates.

  2. 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.

  3. Volume and market share of anti-epileptic drugs in The Netherlands: impact of new drugs.

    NARCIS (Netherlands)

    Knoester, P.D.; Deckers, C.L.P.; Vaart, R. van der; Leufkens, H.G.; Hekster, Y.A.

    2005-01-01

    OBJECTIVE: In the past decade, several new anti-epileptic drugs (AEDs) were introduced in The Netherlands. These new drugs, one of which is lamotrigine, are 6 to 10 times more expensive than conventional anti-convulsants. In 1997, the high cost of lamotrigine, together with a lack of clinical data

  4. 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

  5. Antiepileptic drugs: Impacts on human serum paraoxonase-1.

    Science.gov (United States)

    Beydemir, Şükrü; Demir, Yeliz

    2017-06-01

    Serum paraoxonase (PON1) is a key enzyme related to high-density lipoprotein (HDL)-cholesterol particle. It can prevent the oxidation of low-density lipoprotein (LDL) and HDL. The present article focuses on the in vitro inhibition role of some antiepileptic drugs (AEDs) such as valproic acid, gabapentin, primidone, phenytoin, and levetiracetam on human paraoxonase (hPON1). Therefore, PON1 was purified from human serum with a specific activity of 3976.36 EU/mg and 13.96% yield by using simple chromatographic methods. The AEDs were tested at various concentrations, which showed reduced in vitro hPON1 activity. IC 50 values for gabapentin, valproic acid, primidone, phenytoin, and levetiracetam were found to be 0.35, 0.67, 0.87, 6.3, and 53.3 mM, respectively. K i constants were 0.261 ± 0.027, 0.338 ± 0.313, 0.410 ± 0.184, 10.3 ± 0.001, and 43.01 ± 0.003 mM, respectively. Gabapentin exhibited effective inhibitory activity as compared with the other drugs. The inhibition mechanisms of all compounds were noncompetitive. © 2016 Wiley Periodicals, Inc.

  6. Chronotolerance study of the antiepileptic drug valproic acid in mice

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    Ben-Cherif Wafa

    2012-05-01

    Full Text Available Abstract Background Valproic acid (VPA is an antiepileptic drug widely used for the treatment of absence seizures and generalized tonic-clonic seizures. The present work aims to study whether VPA-induced toxicity varies according to the dosing-time in the 24 hour-scale. Methods The influence of dosing-time on tolerance to VPA was investigated in 120 male Swiss mice synchronized under a light-dark cycle (12:12. The mean VPA lethal dose was first determined to be 850 ± 0.2 mg/kg, i.p.. Such a dose was administered by i.p. route to a total of 90 mice divided in six circadian stages [1, 5, 9, 13, 17 and 21 Hours After Light Onset (HALO] (15 mice/circadian time; 30 mice were used as control (5 mice / circadian time. Results The surviving treated mice exhibited a significant circadian variation in rectal temperature and body weight loss (p 2 = 42.1, p  Conclusions With regards to these data the optimal tolerance to VPA occurred when the drug was administered in the second half of the light-rest span of mice which is physiologically analogous to the second half of the night for human patients.

  7. Severe cutaneous adverse reactions to antiepileptic drugs in Asians.

    Science.gov (United States)

    Yang, C-Y; Dao, R-L; Lee, T-J; Lu, C-W; Yang, C-H; Hung, S-I; Chung, W-H

    2011-12-06

    Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)-induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs. A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes. Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS. CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Interactions between cannabidiol and commonly used antiepileptic drugs.

    Science.gov (United States)

    Gaston, Tyler E; Bebin, E Martina; Cutter, Gary R; Liu, Yuliang; Szaflarski, Jerzy P

    2017-09-01

    To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs. In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The Mixed Procedure was used to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose. AEDs with interactions seen in initial analysis were plotted for mean change in serum level over time. Subanalyses were performed to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate. Increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p Epilepsy.

  10. Placental passage of antiepileptic drugs at delivery and neonatal outcomes.

    Science.gov (United States)

    Bank, Anna M; Stowe, Zachary N; Newport, D Jeffrey; Ritchie, James C; Pennell, Page B

    2017-05-01

    Children of women treated with antiepileptic drugs (AEDs) are at increased risk of adverse outcomes detectable in the neonatal period, which may be associated with the amount of AEDs in the fetal circulation. Placental passage of AEDs can be measured by calculating the ratio of umbilical cord to maternal AED concentrations collected at delivery. The aims of this study were to determine the umbilical cord concentrations and umbilical-to-maternal ratios for AEDs, and whether higher cord concentrations are associated with increased risk of neonatal complications. AED cord and maternal blood concentrations from 70 mother-newborn dyads and neonatal complications were recorded. Logistic regressions were performed to determine the association between AED concentrations and complications. Mean umbilical-to-maternal ratios for total concentrations ranged from 0.79 for carbamazepine to 1.20 for valproic acid, and mean umbilical-to-maternal ratios for free concentrations ranged from 0.86 for valproic acid to 1.42 for carbamazepine, indicating complete placental passage. Neither umbilical cord concentrations nor umbilical-to-maternal ratios were associated with adverse neonatal outcomes. Additional investigations are warranted to delineate the relationship between quantified fetal AED exposure and neonatal complications. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. 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

  12. Economic evaluation of antiepileptic drug therapy: a methodologic review.

    Science.gov (United States)

    Levy, Pierre

    2002-05-01

    The increasing number of antiepileptic drugs (AEDs) fostered the development of economic studies in epilepsy. We reviewed this literature to identify and discuss methodologic issues. We included all studies devoted to cost-based evaluation in epilepsy, published in English from 1989 to 2001, and identified via a Medline search. We identified a series of methodologic problems. First, we reconsidered heterogeneity of concepts and estimating methods, often cited as the most critical problem, as they do not necessarily result from a failure to apply standard methods. One must distinguish "natural" sources of heterogeneity arising from the many unconstrained choices left open in the implementation of economic evaluation on the one hand, and imperfect information and observation-based sources of heterogeneity leading to constrained choices on the other hand. By their very nature, cost-of-illness studies are subject to this variety of choices and were used to illustrate our purpose. Second, cost-minimization studies were reviewed, as they raise additional problems related to study design and choice of an outcome measure. Finally, deficiencies were also identified in cost-effectiveness and cost-utility studies concerning attempts to incorporate patient's point of view in outcome measurement. We agreed with previous reviews on the difficulty of compare results from economic studies in epilepsy due to heterogeneity in methods and concepts used. This is partly due to imperfect information and limits in observation as sources for data collection, as well as to unavailability of refined outcome measures. Therefore, improvements are possible in this field.

  13. 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)?

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

    Directory of Open Access Journals (Sweden)

    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.

  15. [Antiepileptic drugs in the treatment of autistic regression syndromes].

    Science.gov (United States)

    García-Peñas, J J

    2005-01-15

    It is still not known whether epilepsy or subclinical epileptiform activity can generate autistic regression in children with pervasive development disorder (PDD) in a similar manner to the way linguistic and neurocognitive regression are produced in patients with Landau-Kleffner syndrome and electrical status epilepticus during slow-wave sleep (ESES). Data on the use of different antiepileptic drugs (AED) in Landau-Kleffner syndrome and in ESES is contradictory, but it has been proved that courses of polytherapy clearly have a harmful effect. It has been suggested that the suppression of subclinical epileptiform activity by the early use of AED can revert the disorders affecting behaviour, cognition and language in these patients. Nevertheless, few studies have been conducted to examine the influence of AED therapy on the clinical course of children with PDD and autistic regression and evidence of epileptiform activity in video-EEG-polygraph recordings during sleep. Cases of complete recovery or significant improvement following the use of AED such as valproate, ethosuximide, clobazam, oxcarbazepine, sulthiame, levetiracetam, topiramate or lamotrigine have been reported. Moreover, striking and sustained improvements have been reported with courses of corticoids or ACTH. Yet, we still do not know whether the natural history of PDD with autistic regression is linked to the persistence of epileptiform anomalies in the video-EEG-polygraph recordings or not, and it is therefore difficult to draw conclusions about whether early AED therapy should be established in these patients. In our own clinical experience, lamotrigine has proved to be a good therapeutic alternative for the treatment of patients with autistic regression and paroxysmal anomalies in the EEG recordings, and offers a suitable balance between effectiveness and safety.

  16. Cellular Effects of the Antiepileptic Drug Valproic Acid in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Marita Eckert

    2017-12-01

    Full Text Available Background/Aims: Valproic acid (VPA, an anticonvulsant and mood-stabilizing drug is used to treat epileptic seizure of glioblastoma patients. Besides its antiepileptic activity, VPA has been attributed further functions that improve the clinical outcome of glioblastoma patients. Those comprise the inhibition of some histone deacetylase (HDAC isoforms which reportedly may result in radiosensitization. Retrospective analysis of patient data, however, could not unequivocally confirm a prolonged survival of glioblastoma patients receiving VPA. The present study aimed to identify potential VPA targets at the cellular level. Methods: To this end, the effect of VPA on metabolism, Ca2+-, biochemical and electro-signaling, cell-cycling, clonogenic survival and transfilter migration was analyzed in three human glioblastoma lines (T98G, U-87MG, U251 by MTT assay, Ca2+ imaging, immunoblotting, patch-clamp recording, flow cytometry, delayed plating colony formation and modified Boyden chamber assays, respectively. In addition, the effect of VPA on clonogenic survival of primary glioblastoma spheroid cultures treated with temozolomide and fractionated radiation was assessed by limited dilution assay. Results: In 2 of 3 glioblastoma lines, clinical relevant concentrations of VPA slightly slowed down cell cycle progression and decreased clonogenic survival. Furthermore, VPA induced Ca2+ signaling which was accompanied by pronounced K+ channel activity and transfilter cell migration. VPA did not affect metabolic NAD(PH formation or radioresistance of the glioblastoma lines. Finally, VPA did not impair clonogenic survival or radioresistance of temozolomide-treated primary spheroid cultures. Conclusions: Combined, our in vitro data do not propose a general use of VPA as a radiosensitizer in anti-glioblastoma therapy.

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

    OpenAIRE

    Ghaydaa A Shehata; Abd El-aziz M Bateh; Sherifa A Hamed; et al

    2009-01-01

    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 asse...

  18. 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

  19. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study

    OpenAIRE

    Meador, Kimford J; Baker, Gus A; Browning, Nancy; Cohen, Morris J; Bromley, Rebecca L; Clayton-Smith, Jill; Kalayjian, Laura A; Kanner, Andres; Liporace, Joyce D; Pennell, Page B; Privitera, Michael; Loring, David W

    2013-01-01

    Background: Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. Methods: In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and Februa...

  20. Psychiatric side effects and antiepileptic drugs: Observations from prospective audits.

    Science.gov (United States)

    Stephen, Linda J; Wishart, Abbie; Brodie, Martin J

    2017-06-01

    Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have

  1. 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.

  2. Antiepileptic drugs as prophylaxis for post-craniotomy seizures.

    Science.gov (United States)

    Weston, Jennifer; Greenhalgh, Janette; Marson, Anthony G

    2015-03-04

    The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure may vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. Searches were run for the original review in January 2012. We performed subsequent searches in September 2012 and up to 04 August 2014. We searched the Cochrane Epilepsy Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE. We did not apply any language restrictions. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. Trials with adequate randomisation methods and concealment were included; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. Two review authors (JP and JG) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of patients experiencing seizures (early - occurring within first week following craniotomy, and late - occurring after first week following craniotomy), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a

  3. The impact of different antiepileptic drugs on the sedation of children during magnetic resonance imaging

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    Isil Davarci

    2014-10-01

    Full Text Available Background and objectives:The induction and inhibition of cytochrome P450 isoenzymes by antiepileptic drugs lead to changes in the clearance of anesthetic drugs eliminated via hepatic metabolism. We investigated the duration of the sedation and additional anesthetic needs during magnetic resonance imaging in epileptic children receiving antiepileptic drugs that cause either enzyme induction or inhibition.Methods:In American Society of Anesthesiology I–II, 120 children aged 3–10 years were included. Group 1: children using antiepileptic drugs that cause cytochrome P450 enzyme induction; Group 2: those using antiepileptic drugs that cause inhibition; and Group 3: those that did not use antiepileptic drugs. Sedation was induced with the use of 0.05 mg kg−1 midazolam and 1 mg kg−1 propofol. An additional 0.05 mg kg−1 of midazolam and rescue propofol (0.5 mg kg−1 were administered and repeated to maintain sedation. The duration of sedation and the additional sedation needed were compared.Results:The duration of the initial dose was significantly shorter in Group I compared with groups II and III (p = 0.001, p = 0.003, respectively. It was significantly longer in Group II compared with groups I and III (p = 0.001, p = 0.029, respectively. The additional midazolam needed for adequate sedation was increased in Group I when compared with groups II and III (p = 0.010, p = 0.001, respectively. In addition, the rescue propofol dose was significantly higher only in Group I when compared with Group III (p = 0.002.Conclusion:In epileptic children, the response variability to the initial sedative agents during the magnetic resonance imaging procedure resulting from the inhibition or induction of the cytochrome P450 isoenzymes by the antiepileptic drugs mandated the titration of anesthetic agents.

  4. Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs

    DEFF Research Database (Denmark)

    Madsen, Karsten K; Clausen, Rasmus P; Larsson, Orla M

    2009-01-01

    Inhibition of the GABA transporter subtype GAT1 by the clinically available anti-epileptic drug tiagabine has proven to be an effective strategy for the treatment of some patients with partial seizures. In 2005, the investigational drug EF1502 was described as possessing activity at both GAT1...

  5. 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

  6. MAJOR PRINCIPLES OF EPILEPSY TREATMENT. ALGORITHM OF SELECTION OF ANTIEPILEPTIC DRUGS

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2014-01-01

    Full Text Available The authors reviewed general principles of epilepsy treatment in details as well as provided their proprietary algorithm of selection of antiepileptic drugs developed Svt. Luka's Institute of Child Neurology and Epilepsy. This algorithm is designed for general practitioners that deal with treatment of epilepsy. In the course of selection of the first antiepileptic drug, the doctor must take into consideration the age of the patient, assess their level of development, clinical manifestations of seizures, data of electroencephalography and magnetic resonance imaging. The data received allows determination of the type of seizures, supposing of the syndrome-related diagnosis, and selection of the most appropriate antiepileptic drug of first choice in each specific case. There are also recommendations for further examination of patients and monitoring of efficacy of therapy.

  7. Drug-Drug Interactions Among Hospitalized Children Receiving Chronic Antiepileptic Drug Therapy.

    Science.gov (United States)

    Lebowitz, Mollie Blazar; Olson, Karen L; Burns, Michele; Harper, Marvin B; Bourgeois, Florence

    2016-05-01

    Children treated with chronic medications are at risk of drug-drug interactions (DDIs) when hospitalized with an acute illness and prescribed new medications. We aimed to measure the prevalence of potential DDIs (pDDIs) among hospitalized children treated with antiepileptic drugs (AEDs) and to evaluate the impact of computerized physician order entry (CPOE) on pDDIs. We analyzed a national sample of pediatric hospitalizations from 2005 to 2012 associated with administration of an AED and identified those prescribed a second medication with risk of a DDI. The prevalence of hospitalizations associated with a pDDI was calculated for each AED. We identified the drugs most commonly implicated in pDDIs and factors associated with pDDIs. Rates of pDDIs were measured in pre- and post-CPOE implementation periods. A pDDI was identified in 181 380 (41.7%) hospitalizations associated with the use of an AED, with 117 880 (27.1%) classified as severe pDDIs. AEDs most often implicated with a pDDI were phenobarbital, valproic acid, and phenytoin. Hospitalizations with pDDIs were associated with increased length of stay and a greater number of medications, ICU admissions, and operating room procedures. The implementation of CPOE did not result in a change in the rate of pDDIs (42.7% before versus 40.8% after; P = .48). Children treated with AEDs are at risk of pDDIs while hospitalized. The use of CPOE has not been associated with a significant decrease in the rate of pDDIs. Additional investigation to better define the impact of pDDIs and to advance development of clinical decision support within CPOE systems is warranted. Copyright © 2016 by the American Academy of Pediatrics

  8. 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

  9. 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 ...

  10. Morphological Pattern of Cutaneous Adverse Drug Reactions due to Antiepileptic Drugs in Eastern India

    Science.gov (United States)

    Singh, Punit Kumar; Kumar, Dharmendra; Kumar, Prashant

    2015-01-01

    Introduction: Cutaneous manifestations of adverse drug reactions are a common occurrence and need to be differentiated from other causes of similar manifestations. Antiepileptic drugs (AED) usually are responsible for severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophillia and systemic symptoms (DRESS). There is paucity of published research regarding morphological pattern of CADR due to various antiepileptic drugs AED. Objective: To study the morphological patterns of CADR due to AED and common anticonvulsant drugs implicated particularly in severe CADR such as SJS/TEN and DRESS in a tertiary care teaching hospital in eastern India. Materials and Methods: A prospective, observational study was conducted over a period of 4 years from August 2009 to July 2013 after the approval of the Institutional Ethics Committee using self-reporting method for selection of cases. Settings: All patients with CADR after AED consumption for various conditions presenting to the Dermatology outpatient department (OPD) and Pediatric OPD and Indoor patients of a tertiary care teaching hospital located in Rohtas district of Bihar were included in this study. Results: During the study period, 64 cases of severe CADRs were included in this study. Out of 64 patients, 28 were male and 36 were female with mean age 36.1 years (range 6 years to 72 years). Most common AED implicated for CADR was Phenytoin. Maculopapular rash was the most common cutaneous manifestation of ADRs (42.85%). Serious CADR like TEN and SSJS were more likely in patients prescribed Phenytoin and Carbemazepine simultaneously. Conclusion: CADRs are a common occurrence and awareness about the same is essential for diagnosis and prevention. This study identified combined use of phenytoin and carbamezepine as a most important risk factor for serious CADR like SJS and TEN. PMID:25738068

  11. Antiepileptic Drugs-induced Stevens?Johnson syndrome: A case Series

    OpenAIRE

    Trivedi, Bhavi S.; Darji, Nishita H.; Malhotra, Supriya D.; Patel, Pankaj R.

    2016-01-01

    Stevens?Johnson syndrome (SJS) is an acute life-threatening mucocutaneous reaction, characterized by extensive necrosis and detachment of the epidermis from the skin. The overall incidence of SJS is seen in five cases per million people per year. SJS is typically caused by drugs and is a kind of idiosyncratic reaction. Adverse drug reactions such an SJS have a remarkable effect on patient's safety issues. We encountered nine cases of antiepileptic drug (AED)-induced SJS, specifically with car...

  12. 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.

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

    NARCIS (Netherlands)

    De Groot, Mark C.H.|info:eu-repo/dai/nl/313936455; Schuerch, Markus; De Vries, Frank|info:eu-repo/dai/nl/303546670; Hesse, Ulrik; Oliva, Belén; Alvarez, Consuelo Huerta; Gil, Miguel; Requena, Gema; Abajo, Francisco; Afonso, Ana; Souverein, Patrick C.|info:eu-repo/dai/nl/243074948; Alvarez, Yolanda; Slattery, Jim; Rottenkolber, Marietta; Schmiedl, Sven; Van Dijk, Liset; Schlienger, Raymond G.; Reynolds, Robert; Klungel, Olaf|info:eu-repo/dai/nl/181447649

    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

  14. 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

  15. Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age

    Science.gov (United States)

    Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

    2011-01-01

    We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled…

  16. 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

  17. Trends in the use of anti-epileptic drugs during pregnancy in the netherlands

    NARCIS (Netherlands)

    van Puijenbroek, Eugene; de Vries, Loes; Kant, Agnes

    2014-01-01

    Background: The use of anti-epileptic drugs (AEDs) during pregnancy is associated with an increased risk of birth defects. Since epilepsy itself is also associated with potential risks for mother and child, an optimal AED treatment is needed. Over the past years, the introduction of new AEDs and the

  18. 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

    PURPOSE: To assess adverse events with use of antiepileptic drugs (AEDs) by the method of sequence symmetry analysis. METHODS: We used data from two population-based sources in Funen County, Denmark (population 2006: 479 000); prescription data from Odense University Pharmacoepidemiological Datab...

  19. Bone mineral density in adult patients treated with various antiepileptic drugs

    DEFF Research Database (Denmark)

    Beniczky, Simona Alexandra; Viken, Janina; Jensen, Lars Thorbjørn

    2012-01-01

    There is considerable evidence suggesting, that older antiepileptic drugs (AEDs) and some of the newer ones decrease bone mineral density (BMD). However, there is only limited and conflicting data concerning the effect of levetiracetam on BMD. In this cross-sectional study we analysed data from 1...

  20. The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs : A Literature Review

    NARCIS (Netherlands)

    de Jong, Josta; Garne, Ester; Jong-van den Berg, de Lolkje; Wang, Hao

    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

  1. 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

  2. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study.

    Science.gov (United States)

    Bech, Bodil Hammer; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard; Howards, Penelope P; Sørensen, Merete Juul; Olsen, Jørn; Parner, Erik Thorlund; Pedersen, Lars Henning; Vestergaard, Mogens; Christensen, Jakob

    2014-08-21

    To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. Population based cohort study. Register based study in Denmark, 1997-2008. 983,305 pregnancies identified in the Danish medical birth register and the Danish national hospital discharge register from 1 February 1997 to 31 December 2008 were linked to the Danish Register of Medicinal Product Statistics to obtain information on use of antiepileptic drugs. Risk ratio of spontaneous abortion and stillbirth after use of antiepileptic drugs during pregnancy, estimated by using binomial regression adjusting for potential confounders of maternal age, cohabitation, income, education, history of severe mental disorder, and history of drug misuse. Antiepileptic drugs were used in a total of 4700 (0.5%) pregnancies. 16 out of 100 pregnant women using antiepileptics and 13 out of 100 pregnant women not using antiepileptics experienced a spontaneous abortion. After adjusting for potential confounders pregnant women using antiepileptics had a 13% higher risk of spontaneous abortions than pregnant women not using antiepileptics (adjusted risk ratio 1.13, 95% confidence interval 1.04 to 1.24). However, the risk of spontaneous abortion was not increased in women with an epilepsy diagnosis (0.98, 0.87 to 1.09), only in women without a diagnosis of epilepsy (1.30, 1.14 to 1.49). In an analysis including women with at least two pregnancies with discordant antiepileptic drug use (for example, use in the first pregnancy but not in the second), the adjusted hazard ratio for spontaneous abortion was 0.83 (0.69 to 1.00) for exposed pregnancies compared with unexposed pregnancies. Stillbirth was identified in 18 women who used antiepileptic drugs (unadjusted risk ratio 1.29, 0.80 to 2.10). Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies in the same woman, we found no overall association between the use of

  3. [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.

  4. [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.

  5. 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.

  6. 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...

  7. 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

    Epileptic seizure activity is associated with an imbalance between excitatory and inhibitory synaptic activities. The latter is mediated by GABA, and several currently used antiepileptic drugs target entities of the GABAergic synapse such as the receptors or the inactivation mechanism consisting...... 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...... of such transporters pointing in particular to an interesting role of the transporters located extrasynaptically. It is suggested that the betaine-GABA transporter BGT1 should receive particular interest in this context as the GABA analogue EF 1502 (N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-(methylamino)-4...

  8. Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats.

    Science.gov (United States)

    Consroe, P; Wolkin, A

    1977-04-01

    A comparison of the anticonvulsant and neurotoxic effects of cannabidiol (CBD), delta 9tetrahydrocannabinol, cannabinol and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, chlordiazepoxide, clonazepam, ethosuximide and trimethadione) was made in rats. Median effective potencies (ED 50 values) for maximal electroshock, audiogenic seizures and TD50 values for a rotor rod neurotoxicity test were calculated. Additionally, the interactive effects of CBD and the antiepileptic drugs against maximal electroshock and audiogenic seizures were studied. Each drug was given orally at peak effect time. CBD was an effective and relatively potent anticonvulsant in both maximal electroshock and audiogenic seizure tests. The anticonvulsant potency of phenytoin was significantly increased when combined with phenobarbital, CBD and phenobarbital plus CBD. Additionally, CBD reliably reduced the anticonvulsant potencies of chlordiazepoxide, clonazepam, trimethadione and ethosuximide. These data indicate that CBD is an effective anticonvulsant with a specificity more comparable to drugs clinically effective in major than minor seizures. Furthermore, it appears that CBD enhances the anticonvulsant effects of the former and reduces the effects of the latter types of antiepileptic drugs.

  9. Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years

    OpenAIRE

    Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Bromley, Rebecca L.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

    2014-01-01

    IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapymay be harmful.We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospec...

  10. Ilizarov treatment of humeral shaft nonunion in an antiepileptic drug patient with uncontrolled generalized tonic-clonic seizure activity

    Directory of Open Access Journals (Sweden)

    Koulouvaris Panayiotis

    2010-07-01

    Full Text Available Abstract Nonunion of the humeral shaft in patients with antiepileptic drug associated metabolic bone disorder constitute a challenging surgical problem difficult to treat due to seizure activity, osteoporosis, and poor stabilization options. We report a case of nonunion of the humeral shaft in an antiepileptic drug patient with uncontrolled generalized tonic-clonic seizure activity successfully treated with Ilizarov external fixator and a follow-up of 4 years.

  11. An evaluation of the impact of memory and mood on antiepileptic drug adherence.

    Science.gov (United States)

    McAuley, James W; Passen, Nina; Prusa, Christine; Dixon, Joanne; Cotterman-Hart, Sheri; Shneker, Bassel F

    2015-02-01

    Antiepileptic drugs are the mainstay of treatment for patients with epilepsy. Adherence to the prescribed regimen is a major factor in achieving a reduced seizure burden, which can decrease morbidity and mortality. Patients with epilepsy oftentimes complain about difficulty with memory. Because little is known about the relationship between memory and mood and adherence, the purpose of this project was to determine the impact of the confounding factors of memory and mood on antiepileptic drug adherence in patients with epilepsy. One hundred adult patients with epilepsy were recruited from the outpatient neurology clinic for this cross-sectional study. Patients who met the inclusion criteria completed measures of subjective memory (subset of 6 memory questions from the QOLIE-89) and objective memory (Hopkins Verbal Learning Test - Revised), subjective adherence (Morisky scale) and objective adherence (medication possession ratio), and mood (Neurological Disorders Depression Inventory for Epilepsy). Refill records from each patient's community pharmacy were used to objectively assess adherence. Medication possession ratios were calculated based on the antiepileptic drug refill records over the previous 6months. Patients were considered adherent if their MPR was >80%. Women made up the majority of the sample (n=59), and, on average, patients had been living with epilepsy for nearly 20years. Approximately 40% of the sample were on antiepileptic drug monotherapy; most patients (>70%) took their antiepileptic drugs twice daily, and the mean number of total medications was 4.25±2.98. Based on the objective measure of adherence, 35% of the patients were nonadherent. Patients self-reported better adherence than what was objectively measured. Only the retention metric of the objective memory measure differentiated adherent patients from nonadherent patients. Patients in the adherent group had significantly lower depression scores (indicating better mood) compared with those

  12. Antiepileptic drug prescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel; Garne, Ester; Wang, Hao

    2015-01-01

    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. CONCLUSION: The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co...... 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......-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. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd....

  13. 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

    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......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...

  14. Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy.

    Science.gov (United States)

    Dash, Deepa; Aggarwal, Vikas; Joshi, Rupa; Padma, Madakasira Vasantha; Tripathi, Manjari

    2015-04-01

    The present study was conducted with the aim of evaluating the effects of reducing the number of antiepileptic drugs (AEDs) administered to patients with drug-refractory epilepsy (DRE) during their admission and document any change in seizure frequency in subsequent follow up. A total of 962 patients with DRE who were admitted to the neurology wards waiting for connection to video EEG were recruited for this prospective study. After their admission to the neurology ward, modifications in the number and dosage of AEDs were done with a target of a maximum of three AEDs in every patient. Drug tapering was done using a standardized protocol. The primary outcome was the change in seizure frequency in the follow-up period of 6 months. Secondary outcome measures were the adverse event profile (AEP) and the quality of life (QOL). Of the 1134 patients screened, 962 patients gave consent to participate in the study. The mean number of AEDs received by each patient was 4.24. After the tapering following a standardized protocol each patient received a mean of 2.65 AEDs per patient. In 82.70% patients with DRE, there was either a reduction or no change in seizure frequency in the subsequent 6 months follow up. There was a significant reduction in the AEP score after the reduction in the number of AEDs (P = 0. 001). Our study proves that optimization of reduction of the number of AED's in patients with DRE leads to reduction or no change in seizure frequency with a significant decrease in adverse effects. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  15. Prenatal exposure to antiepileptic drugs and dental agenesis.

    Directory of Open Access Journals (Sweden)

    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.

  16. Prenatal exposure to antiepileptic drugs and dental agenesis.

    Science.gov (United States)

    Jacobsen, Pernille E; Henriksen, Tine B; Haubek, Dorte; Østergaard, John R

    2014-01-01

    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. 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. 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. 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.

  17. Evaluation of bone mineral density in children receiving antiepileptic drugs.

    Science.gov (United States)

    Akin, R; Okutan, V; Sarici, U; Altunbas, A; Gökçay, E

    1998-08-01

    The effects of the valproic acid and carbamazepine monotherapies on bone mineral density were evaluated. Bone mineral density was measured in 53 children with primary epilepsy taking either valproic acid (n = 25) or carbamazepine (n = 28) for longer than 1 year and in a healthy control group (n = 26) by the dual-energy x-ray absorptiometry method at L2-L4 levels of lumbar vertebrae. The mean serum levels of valproic acid and carbamazepine were 66 +/- 2.2 microg/mL and 7.0 +/- 9.3 microg/mL, respectively, and the mean duration of treatment for each drug was 2.4 +/- 0.2 years and 2.6 +/- 0.5 years, respectively. Calcium intakes in diet were similar in both the control and study groups. The serum levels of calcium and phosphorus in all groups were normal. Bone mineral density values of both valproic acid and carbamazepine groups were not statistically different from that of the control group (P > 0.05).

  18. A NEW ANTIEPILEPTIC DRUG — ZONEGRAN (ZONISAMIDE — IN THE TREATMENT OF EPILEPSY (A REVIEW

    Directory of Open Access Journals (Sweden)

    O. A. Pylaeva

    2012-01-01

    Full Text Available Despite the considerable advances of epileptology drug-resistant epilepsies consist about 30% among all forms of epilepsy. Authors represent the review of the literature devoted to efficacy and tolerability of zonisamide in the treatment of drug-resistant epilepsy. The current review of studies devoted to efficacy and safety of a new antiepileptic drug zonisamide in the treatment of epilepsy is proposed. The mechanism of action and pharmacokinetic of zonisamide are described; the questions of efficacy and tolerability in the treatment of drug-resistant focal epilepsies and other types of seizures and forms of epilepsy are considered. The possibilities of the use of the drug in the treatment of comorbid disorders are considered

  19. Partial epilepsies: Choice of antiepileptic drugs in adults in the outpatient setting

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2016-01-01

    Full Text Available The paper depicts the author's view on how a neurologist/epileptologist chooses an antiepileptic drug in his practice under present-day conditions. It considers possible clinical situations and therapeutic tactics in relation to the efficiency of performed therapy, as well as methods for switching to other antiepileptic drugs if the previous/first monotherapy is ineffective. The author gives main international and Russian guidelines in terms of the type of epileptic seizure/form of epilepsy/epilepsy syndrome. Despite its almost semicentennial history of effective clinical application, valproate is shown to be now a first-line choice drug for the therapy of undifferentiated, cryptogenic, and symptomatic partial epilepsies in patients of different age groups. The properties of valproate, such as efficacy against different types of seizures and forms of epilepsy, good tolerability, minimal aggravation risk, high monotherapy retention rates, various dosage forms, including the brand-name extendedrelease drug Depakine chrono or Depakine chronosphere and its intravenous formulation, favorable pharmacokinetic and pharmacodynamics profiles, make it indispensable at the present developmental stage of epileptology.

  20. Antiepileptic Drugs-induced Stevens–Johnson syndrome: A case Series

    Science.gov (United States)

    Trivedi, Bhavi S.; Darji, Nishita H.; Malhotra, Supriya D.; Patel, Pankaj R.

    2016-01-01

    Stevens–Johnson syndrome (SJS) is an acute life-threatening mucocutaneous reaction, characterized by extensive necrosis and detachment of the epidermis from the skin. The overall incidence of SJS is seen in five cases per million people per year. SJS is typically caused by drugs and is a kind of idiosyncratic reaction. Adverse drug reactions such an SJS have a remarkable effect on patient's safety issues. We encountered nine cases of antiepileptic drug (AED)-induced SJS, specifically with carbamazepine, oxcarbazepine, and phenytoin. To manage the reaction, the clinician withdrew the drug in all 8 cases, and in 1 case, the patient was shifted to valproate and symptomatic treatment was provided. There is still a controversy whether or not all AEDs can cause SJS. Recent studies have investigated the role of genetic factors - HLAB*502 allele in the development of AED-induced SJS in patients of Asian ancestry. PMID:28104975

  1. Antiepileptic Drugs-induced Stevens-Johnson syndrome: A case Series.

    Science.gov (United States)

    Trivedi, Bhavi S; Darji, Nishita H; Malhotra, Supriya D; Patel, Pankaj R

    2016-12-01

    Stevens-Johnson syndrome (SJS) is an acute life-threatening mucocutaneous reaction, characterized by extensive necrosis and detachment of the epidermis from the skin. The overall incidence of SJS is seen in five cases per million people per year. SJS is typically caused by drugs and is a kind of idiosyncratic reaction. Adverse drug reactions such an SJS have a remarkable effect on patient's safety issues. We encountered nine cases of antiepileptic drug (AED)-induced SJS, specifically with carbamazepine, oxcarbazepine, and phenytoin. To manage the reaction, the clinician withdrew the drug in all 8 cases, and in 1 case, the patient was shifted to valproate and symptomatic treatment was provided. There is still a controversy whether or not all AEDs can cause SJS. Recent studies have investigated the role of genetic factors - HLAB*502 allele in the development of AED-induced SJS in patients of Asian ancestry.

  2. 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.

  3. Relationship of child IQ to parental IQ and education in children with fetal antiepileptic drug exposure.

    Science.gov (United States)

    Meador, Kimford J; Baker, Gus A; Browning, Nancy; Clayton-Smith, Jill; Cohen, Morris J; Kalayjian, Laura A; Kanner, Andres; Liporace, Joyce D; Pennell, Page B; Privitera, Michael; Loring, David W

    2011-06-01

    Clinical trial designs need to control for genetic and environmental influences when examining cognitive outcomes in children for whom clinical considerations preclude randomization. However, the contributions of maternal and paternal IQ and education to pediatric cognitive outcomes are uncertain in disease populations. The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study is an ongoing prospective observational multicenter study in the United States and United Kingdom, which enrolled pregnant women with epilepsy to determine if differential long-term neurodevelopmental effects exist across four commonly used antiepileptic drugs. Here, we examined the relationship of IQ and education in both parents to child IQ at age 3 years. IQ and education for both parents were statistically correlated to child IQ. However, paternal IQ and education were not significant after accounting for maternal IQ effects. Because maternal IQ and education are independently related to child cognitive outcome, both should be assessed in studies investigating the effects of fetal drug exposures or other environmental factors that could affect the child's cognitive outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. New antiepileptic drugs in the treatment of Lennox-Gastaut syndrome

    Directory of Open Access Journals (Sweden)

    Francesco CHIARELLI

    2009-12-01

    Full Text Available Lennox–Gastaut syndrome is a childhood epileptic encephalopathy characterised by polymorphic seizures and neuropsychological decline. The most characteristic seizures are tonic fits, atypical absences and atonic seizures, in that order. Treatment options for patients with LGS are limited because of the resistance of seizures to pharmacological treatment. Owing to the many seizure types, many drugs are used in combinations that are mostly guided by anecdotal evidence or personal experience. Opinions towards treatment are further complicated because an antiepileptic drug might be of some benefit for the control of one type of seizure while aggravating another type. Concomitantly, polytherapy increases the potential for adverse events. The ultimate goal of epilepsy treatment is to achieve seizure control in a safe manner. Seizure freedom appears to be unrealistic in some refractory epilepsies, especially LGS. In this Review, we discuss newer antiepileptic drugs (Felbamate, Lamotrigine, Levetiracetam, Topiramate, Rufinamide, Vigabatrin, Zonisamide in the treatment of Lennox-Gastaut syndrome. Investigation of the effects of newer medications might help to identify treatments that, when used in the early stages of the disorder, might have long-term beneficial effects on seizures and the associated comorbidities.

  5. Adverse reactions to antiepileptic drugs in epileptic outpatients: a cross-sectional study in iran.

    Science.gov (United States)

    Namazi, Soha; Borhani-Haghighi, Afshin; Karimzadeh, Iman

    2011-01-01

    To evaluate the pattern and possible risk factors of adverse reactions to antiepileptic drugs (AEDs) in epileptic outpatients in Iran. We conducted a cross-sectional study for a period of 1 year on epileptic outpatients under antiepileptic therapy. All present adverse drug reactions (ADRs) to antiepileptics and their clinical and paraclinical characteristics were recorded. Causality assessment was performed by the Naranjo algorithm. Seriousness of ADRs was assessed by the World Health Organization's definition. Schumock and Thornton questionnaire was applied to determine the preventability of ADRs. Statistical-descriptive analyses were performed. A total of 1055 adverse reactions to AEDs were recorded from 201 epileptic outpatients. Their mean ± SD age was 28.63 ± 15.06 years. The most frequent detected adverse reactions to AEDs were sedation (7.29%) and amnesia (6.35%). According to the Naranjo algorithm, 604 (57.25%) ADRs were possible. The rate of preventable ADRs was 57%. Only 8 (0.76%) ADRs were identified as serious. No statistically significant association was found between the number of ADRs and age, sex, type of epilepsy, and AED generation (P > 0.05). In contrast, polytherapy was associated with more ADRs than monotherapy (P = 0.039). According to multivariate logistic regression analysis, females were at a higher risk of experiencing an adverse reaction to AEDs than males (odds ratio, 3.676; 95% confidence interval, 1.198-11.283; P = 0.023). Adverse reactions to AEDs were very common among epileptic outpatients. The female sex was identified as a risk factor for experiencing an ADR.

  6. Comparative efficacy and acceptability of antiepileptic drugs for classical trigeminal neuralgia: a Bayesian network meta-analysis protocol.

    Science.gov (United States)

    Qin, Zongshi; Xie, Shang; Mao, Zhi; Liu, Yan; Wu, Jiani; Furukawa, Toshi A; Kwong, Joey S W; Tian, Jinhui; Liu, Zhishun

    2018-01-21

    Trigeminal neuralgia (TN) affects 4 to 28.9/100 000 people worldwide, and antiepileptic drugs such as carbamazepine and oxcarbazepine are the firstline treatment options. However, the efficacy and safety of other antiepileptic drugs remain unclear due to insufficient direct comparisons. To compare the efficacy and acceptability of all currently available antiepileptic agents for the treatment of patients with classical TN. We will search the PubMed, EMBASE, Cochrane Library and Web of Science databases for unpublished or undergoing research listed in registry platforms. We will include all randomised controlled trials comparing two different antiepileptic drugs or one antiepileptic drug with placebo in patients with classical TN. The primary outcomes will be the proportion of responders and the number of subjects who dropout during the treatment. The secondary outcomes will include the two primary outcomes but in the follow-up period, changes in the self-reporting assessment scale for neuralgia and quality of life assessment. In terms of network meta-analysis, we will fit our model to a Bayesian framework using the JAGS and pcnetmeta packages of the R project. This protocol will not disseminate any private patient data. The results of this review will be disseminated through peer reviewed publication. CRD42016048640. © 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.

  7. 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.

  8. Experience-based teaching of therapeutics and clinical pharmacology of antiepileptic drugs. Sudden unexplained death in epilepsy: do antiepileptic drugs have a role?

    Science.gov (United States)

    Lathers, C M; Schraeder, P L

    1995-06-01

    The contents of this paper have been written to be used in a teaching program specifically designed for medical postgraduate education of resident physicians and fellows in training interested in the clinical pharmacology of antiepileptic drugs and their role in the treatment of epilepsy and/or in the prevention of sudden unexpected death associated with this disease. With some modifications, such as a specific lecture to provide an overview of the numerous concepts presented in the text, the article could be used when teaching fourth-year medical students. The format of the paper is a combination of didactic review and eight case reports in a self-learning format. A quiz for self-assessment is included at the end of the article (see Appendix). This material was covered in part in the 1992 Board Review Course for Clinical Pharmacology sponsored by the American College of Clinical Pharmacology. The format or setting of instruction for this material could include small learning groups composed of 10 to 15 students. When used in combination with other topics prepared in similar formats, this could become a take home course for those preparing to take the Boards in Clinical Pharmacology. Each instructor could select specific publications from the reference list for assigned readings depending upon the material emphasized by the instructor. The questions included at the end of the text could be used as either a closed or an open book quiz to assess student learning.

  9. Newer Antiepileptic Drugs for Status Epilepticus in Adults: What's the Evidence?

    Science.gov (United States)

    Beuchat, Isabelle; Novy, Jan; Rossetti, Andrea O

    2018-03-01

    Status epilepticus (SE) is one of the most frequent neurological emergencies. Despite this, understanding of its pathophysiology and evidence regarding its management is limited. Rapid, effective, and well-tolerated treatment to achieve seizure cessation is advocated to prevent brain damage or potentially lethal outcomes. The last two decades have witnessed an exponential increase in the number of available antiepileptic drugs (AEDs). These compounds, especially lacosamide and levetiracetam, in view of their intravenous formulation, have been increasingly prescribed in SE. These and other newer AEDs present a promising profile in terms of tolerability, with few centrally depressive effects, favorable pharmacokinetic properties, and fewer drug interactions than classical AEDs; conversely, they are more expensive. There is still no clear evidence to suggest a specific beneficial impact of newer AEDs on SE outcome, preventing any strong recommendation regarding their prescription in SE. Further comparative studies are urgently required to clarify their place and optimal use in the armamentarium of SE treatment.

  10. An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

    Science.gov (United States)

    Fong, J Ky; Chan, E Ly; Leung, H; Chan, I; Chang, R Sk; Fong, G Cy; Fung, E Lw; Lui, C Ht; Fung, B Bh; Poon, T L; Siu, D; Wong, H T; Yeung, E; Yung, A Wy; Zhu, C Xl

    2017-02-01

    New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine

  11. 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

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

    Science.gov (United States)

    Shehata, Ghaydaa A; Bateh, Abd El-aziz M; Hamed, Sherifa A; Rageh, Tarek A; Elsorogy, Yaser B

    2009-01-01

    To evaluate the effect of antiepileptic drugs (AEDs) on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. 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. 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). This study provides support for the notion that AEDs can impair performance in cognition, mood and behavior. Duration of drug intake and the number of the utilized AEDs are the main confounding variables. This study did not provide clues on how to exclude the effect of epilepsy itself and psychosocial variables as additional important confounding variables.

  13. 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...

  14. 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

  15. 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...

  16. 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.

  17. 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...

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

    International Nuclear Information System (INIS)

    Hakyemez, B.; Erdogan, C.; Yildirim, N.; Gokalp, G.; Parlak, M.

    2005-01-01

    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

  19. 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.

  20. 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.

  1. 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 pWHS seizures. This study design is susceptible to possible bias, as the data are largely drawn from caregiver report and investigators had limited access to medical records. Despite this, our data suggest that the genetic etiology of seizures, together with an accurate electroclinical delineation, are important components of drug selection, even in contiguous gene syndromes which may have complex seizure etiologies

  2. 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

  3. The Need for Antiepileptic Drug Chronotherapy to Treat Selected Childhood Epilepsy Syndromes and Avert the Harmful Consequences of Drug Resistance

    Directory of Open Access Journals (Sweden)

    Sheryl Manganaro

    2017-02-01

    Full Text Available Antiepileptic drug (AED chronotherapy involves the delivery of a greater AED dose at the time of greatest seizure susceptibility usually associated with predictable seizure peaks. Although research has proven AED chronotherapy, commonly known as differential dosing, to be safe, well tolerated, and highly effective in managing cyclic seizure patterns in selected childhood epilepsies, conventional, equally divided AED dosing remains the standard of care. Differential dosing is more often applied in the emergency management of acute seizure clustering resulting from drug resistance—a harmful epilepsy-related consequence that affects 30% of children. Moreover, drug resistance is a major risk factor in status epilepticus and sudden, unexpected death in epilepsy. Although these facts should promote the wider use of differential dosing in selected cases, a credible hypothesis is needed that defines the differential dosing strategy and application in cyclic epilepsy and for the greater purpose of preventing harmful outcomes.

  4. Patients' perspectives on management and barriers of regular antiepileptic drug intake.

    Science.gov (United States)

    May, Theodor W; Berkenfeld, Ralf; Dennig, Dieter; Scheid, Brigitte; Hausfeld, Heiko; Walther, Sonja; Specht, Ulrich

    2018-02-01

    The aim of our study was to assess the management of drug intake and potential barriers to adherence reported by two different patient groups. The study was performed in cooperation with the Regional Chamber of Pharmacists of Rhineland-Palatinate and three neurologists in private practice specialized in epileptology. In total, 108 patients surveyed in 43 pharmacies (Group P) and 118 patients treated by the specialized neurologists (Group N) completed anonymously a questionnaire on intake of antiepileptic drugs (AEDs). The statistical evaluation was performed using nonparametric tests and logistic regression analyses. Group N more often used adherence aids, compared with Group P (68.6% vs. 46.3%, pproblems with the regular intake of their medication did not differ significantly between groups (Group N vs. P: 47.0% vs. 40.0%). If patients noticed that they missed a dose, 45.3% completely skipped the missed dose (Group N vs. P: 43.0% vs. 48.1%, n.s.). In a multivariate analysis, significant risk factors of problems with regular drug intake were ageproblems with adherence than patients surveyed in pharmacies. Since barriers for a regular intake are diverse, the use of a short questionnaire on management of drug intake may lead to an individually tailored counseling of patients to improve adherence. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Solid Dispersion Approach Improving Dissolution Rate of Stiripentol: a Novel Antiepileptic Drug.

    Science.gov (United States)

    Afifi, Samar

    2015-01-01

    Some drugs have low bioavailability due to their poor aqueous solubility and/or slow dissolution rate in biological fluids. Stiripentol (STP) is a novel anticonvulsant drug that is structurally unrelated to the currently available antiepileptics. It has poor aqueous solubility and its solubility has to be enhanced accordingly. Polyethyleneglycol 6000 (PEG-6000) is commonly utilized as a hydrophilic carrier for poorly water soluble drugs in order to improve their bioavailability. STP and PEG-6000 binary system was obtained by physical mixture, solvent evaporation, co-evaporation and melting methods using different weight ratios. The properties of the prepared binary systems were evaluated using dissolution rate, phase solubility, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) studies. The FTIR spectroscopic studies showed the stability of STP and absence of STP-PEG-6000 interaction. The DSC and SEM studies indicated the amorphous state of STP in its binary systems with PEG-6000. Dissolution profile of STP was significantly improved via complexation with PEG-6000 as compared with the pure drug. The binary system which was prepared using melting method showed the highest dissolution rate. The promising results of the prepared binary systems open the avenue for further oral formulation of STP.

  6. Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence

    Directory of Open Access Journals (Sweden)

    Mula M

    2011-06-01

    Full Text Available Marco Mula1, Dale C Hesdorffer21Department of Clinical and Experimental Medicine, Amedeo Avogadro University and Division of Neurology, University Hospital Maggiore della Carità, Novara, Italy; 2Gertrude H Sergievsky Center and Department of Epidemiology, Columbia University, New York, NY, USAAbstract: Two years after the warning issued by the Food and Drug Administration on an increased risk of suicide for people taking antiepileptic drugs (AEDs, a number of pharmacoepidemiologic studies have been published but the scientific community is far from definitive answers. The present paper is aimed at reviewing available evidence on the association between AEDs and suicidal behavior, discussing major variables involved such as the relationship between epilepsy, depression, and suicide and the psychotropic potential of AEDs. All studies published so far show a lack of concordance and are constrained by various methodological limitations. What seems to be established is that mood disorders represent a frequent comorbidity in epilepsy and suicide is a serious complication more frequently encountered in epilepsy rather than in the general population. Moreover, a subgroup of patients appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. The prior history of suicide attempt, especially preceding the onset of the epilepsy, may represent a key element explaining why what is observed is independent of the specific mechanism of the drug. In general terms, risks associated with stopping, or not even starting, AEDs in epilepsy might well be in excess of the risk of suicide in epilepsy, as deaths due to accident and epilepsy itself may predominate. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters (eg, age, gender, working needs, medical comorbidities, history of

  7. Interlaboratory variability in the quantification of new generation antiepileptic drugs based on external quality assessment data.

    Science.gov (United States)

    Williams, John; Bialer, Meir; Johannessen, Svein I; Krämer, Günther; Levy, René; Mattson, Richard H; Perucca, Emilio; Patsalos, Philip N; Wilson, John F

    2003-01-01

    To assess interlaboratory variability in the determination of serum levels of new antiepileptic drugs (AEDs). Lyophilised serum samples containing clinically relevant concentrations of felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), the monohydroxy derivative of oxcarbazepine (OCBZ; MHD), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were distributed monthly among 70 laboratories participating in the international Heathcontrol External Quality Assessment Scheme (EQAS). Assay results returned over a 15-month period were evaluated for precision and accuracy. The most frequently measured compound was LTG (65), followed by MHD (39), GBP (19), TPM (18), VGB (15), FBM (16), and TGB (8). High-performance liquid chromatography was the most commonly used assay technique for all drugs except for TPM, for which two thirds of laboratories used a commercial immunoassay. For all assay methods combined, precision was MHD, FBM, TPM, and LTG, close to 15% for GBP and VGB, and as high as 54% for TGB (p methods, except for TPM, for which gas chromatography showed poorer accuracy compared with immunoassay and gas chromatography-mass spectrometry. With the notable exception of TGB, interlaboratory variability in the determination of new AEDs was comparable to that reported with older-generation agents. Poor assay performance is related more to individual operators than to the intrinsic characteristics of the method applied. Participation in an EQAS scheme is recommended to ensure adequate control of assay variability in therapeutic drug monitoring.

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

    OpenAIRE

    Halvorsen, Kjell H.; Landmark, Cecilie Johannessen; Granås, Anne Gerd

    2016-01-01

    Published version, source at: http://dx.doi.org/10.1155/2016/5153093 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...

  9. 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

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

    Science.gov (United States)

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

    2017-02-01

    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. 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. A total of 42 patients were included and assigned into AED and non-AED treatment groups in a 1:2 matched case-control study. Results show that the seizure outcome after 1 year of AED treatment is not significantly different from that of the control. In the subgroup analysis of patients with subcortical calcifications, the seizure outcome is still not significantly different from that of the control. Thus, AED treatment cannot improve the seizure outcomes in children with parathyroid disorder, even in such cases as suspected structural seizure caused by subcortical calcifications. Clinicians must take adequate considerations on the use of AEDs in these patients. Epileptic seizures, as the first symptom of hypoparathyroidism in children, do not require epilepsy drugs.

  11. 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.

  12. [Gabaergic hypothesis of epilepsy and clinical experience: controversial actions of the new generation gabamimetic antiepileptic drugs].

    Science.gov (United States)

    Chmielewska, B

    2000-01-01

    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well-tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring

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

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    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.

  14. 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.

  15. 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.

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

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    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.

  17. A pilot randomized controlled clinical trial to improve antiepileptic drug adherence in young children with epilepsy.

    Science.gov (United States)

    Modi, Avani C; Guilfoyle, Shanna M; Mann, Krista A; Rausch, Joseph R

    2016-03-01

    The primary aim was to examine the preliminary efficacy of a family tailored problem-solving intervention to improve antiepileptic drug (AED) adherence in families of children with new-onset epilepsy. Secondary aims were to assess changes in targeted mechanisms and treatment feasibility and acceptability. Fifty families (M(age) = 7.6 ± 3.0; 80% Caucasian; 42% idiopathic localization related) completed baseline questionnaires and were given an electronic monitor to observe daily AED adherence. If adherence was ≤ 95% in the first 7 months of the study, families were randomized (Supporting Treatment Adherence Regimens (STAR): n = 11; Treatment as Usual (TAU): n = 12). Twenty-one families were not randomized due to adherence being ≥95%. The STAR intervention included four face-to-face and two telephone problem-solving sessions over 8 weeks. Significant group differences in adherence were found during active intervention (weeks 4-6; TAU = -12.0 vs. STAR = 18.1, p < 0.01; and weeks session 6-8: TAU = -9.7 vs. STAR = 15.3, p < 0.05). Children who received the STAR intervention exhibited improved adherence compared to children in the TAU group during active treatment. Significant changes in epilepsy knowledge and management were noted for the STAR group. Families expressed benefitting from the STAR intervention. Future studies should include a larger sample size and booster intervention sessions to maintain treatment effects over time. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  18. Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs.

    Science.gov (United States)

    Sarangi, Sudhir Chandra; Tripathi, Manjari; Kakkar, Ashish Kumar; Gupta, Yogendra Kumar

    2016-03-01

    Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs. The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed. Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, pcomposition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (pcomposition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701).

  19. Does in utero exposure of antiepileptic drugs lead to failure to reach full cognitive potential?

    Science.gov (United States)

    McCorry, D; Bromley, R

    2015-05-01

    A clinical scenario of a young female on 800 mg of sodium valproate (VPA) who has recently failed lamotrigine (LTG) and levetiracetam (LEV) and who is currently planning a pregnancy is presented. Currently available data pertaining to the longer-term development of children exposed to antiepileptic drugs (AEDs) are reviewed along with considerations around the methodology and interpretation of such research. There is an accumulation of data highlighting significant risks associated with prenatal exposed to VPA, with the level of risk being mediated by dose. The majority of published evidence does not find a significant risk associated with carbamazepine (CBZ) exposure in utero for global cognitive abilities however the evidence for more specific cognitive skills are unclear. Limited data indicate that LTG may be a preferred treatment to VPA in terms of foetal outcome but further evidence is required. Too little data pertaining to LEV exposure is available and a lack of evidence regarding risk of this and other new AEDs should not be interpreted as evidence of safety. Copyright © 2015. Published by Elsevier Ltd.

  20. Studies on the effects of acetylcholine and antiepileptic drugs on /sup 32/P incorporation into phospholipids of rat brain synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Aly, M.I.; Abdel-Latif, A.A.

    1982-02-01

    Studies were conducted on the effects of antiepileptic drugs on the acetylcholine-stimulated /sup 32/P labeling of phospholipids in rat brain synaptosomes. Of the four antiepileptic drugs investigated in the present study, namely phenytoin, carbamazepine, phenobarbital, and valproate, only phenytoin blocked the acetylcholine-stimulated /sup 32/P labeling of phosphatidylinositol and phosphatidic acid, and the acetylcholine-stimulated breakdown of polyphosphoinositides. Phenytoin alone, like atropine alone, had no effect on the /sup 32/P labeling of phospholipids nor on the specific radioactivity of (/sup 32/P)ATP. Omission of Na/sup +/ drastically reduced both the /sup 32/P labeling of synaptosomal phospholipids and the specific radioactivity of (/sup 32/P)ATP and furthermore it significantly decreased the phosphoinositide effect. It was concluded that certain antiepileptic drugs, such as phenytoin, could exert their pharmacological actions through their antimuscarinic effects. In addition the finding that phenytoin, which acts to regulate NA/sup +/ and Ca/sup 2 +/ permeability of neuronal membranes, also inhibited the phosphoinositide effects in synaptosomes, support the conclusions that Ca2+ and Na+ are probably involved in the molecular mechanism underlying this phenomenon in excitable tissues.

  1. 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)....

  2. Effects of antiepileptic drugs on associative LTP-like plasticity in human motor cortex.

    Science.gov (United States)

    Heidegger, Tonio; Krakow, Karsten; Ziemann, Ulf

    2010-10-01

    Antiepileptic drugs (AEDs) are used extensively in clinical practice but relatively little is known on their specific effects at the systems level of human cortex. Here we tested, using a double-blind randomized placebo-controlled crossover design in healthy subjects, the effects of a single therapeutic oral dose of seven AEDs with different modes of action (tiagabine, diazepam, gabapentin, lamotrigine, topiramate, levetiracetam and piracetam) on long-term potentiation (LTP)-like motor cortical plasticity induced by paired associative transcranial magnetic stimulation (PAS). PAS-induced LTP-like plasticity was assessed from the increase in motor evoked potential amplitude in a hand muscle contralateral to the stimulated motor cortex. Levetiracetam significantly reduced LTP-like plasticity when compared to the placebo condition. Tiagabine, diazepam, lamotrigine and piracetam resulted in nonsignificant trends towards reduction of LTP-like plasticity while gabapentin and topiramate had no effect. The particularly depressant effect of levetiracetam is probably explained by its unique mode of action through binding at the vesicle membrane protein SV2A. Enhancement of gamma-amino butyric acid-dependent cortical inhibition by tiagabine, diazepam and possibly levetiracetam, and blockage of voltage-gated sodium channels by lamotrigine, may also depress PAS-induced LTP-like plasticity but these mechanisms appear to be less relevant. Findings may inform about AED-related adverse effects on important LTP-dependent central nervous systems processes such as learning or memory formation. The particular depressant effect of levetiracetam on LTP-like plasticity may also relate to the unique properties of this drug to inhibit epileptogenesis, a potentially LTP-associated process. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  3. 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.

  4. 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.

  5. 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

  6. Induction of nuclear receptors and drug resistance in the brain microvascular endothelial cells treated with antiepileptic drugs.

    Science.gov (United States)

    Lombardo, Laura; Pellitteri, Rosalia; Balazy, Michael; Cardile, Venera

    2008-05-01

    Our work contributes to the understanding of the mechanisms of drug resistance in epilepsis. This study aimed to investigate i) the levels of expression of P-glycoprotein (P-gp), and multidrug resistance-associated proteins (MRP)1 and 2, ii) the activation of the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), and iii) the relationship between increased P-gp and MRPs expression and PXR and CAR activation, in immortalized rat brain microvascular endothelial cell lines, GPNT and RBE4, following treatment with the antiepileptic drugs (AEDs), topiramate, phenobarbital, carbamazepine, tiagabine, levetiracetam, and phenytoin, using Western blotting and immunocytochemistry methods. Carbamazepine, phenobarbital and phenytoin induced the highest levels of P-gp and MPRs expression that was associated with increased activation of PXR and CAR receptors as compared to levetiracetam, tiagabine and topiramate. We conclude that P-gp and MRPs are differently overexpressed in GPNT and RBE4 by various AEDs and both PXR and CAR are involved in the drug-resistant epilepsy induced by carbamazepine, phenobarbital and phenytoin.

  7. 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

  8. 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.

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

    Science.gov (United States)

    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 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.

  10. The importance of assessing behaviour and cognition in antiepileptic drug trials in children and adolescents.

    Science.gov (United States)

    Lagae, Lieven

    2017-06-01

    It has long been recognised that uncontrolled childhood epilepsy is detrimental to cognition and behaviour, impacting on a patient's ability to succeed academically. Patients who experience more frequent and serious seizures are at greater risk for cognitive decline, emphasising the need for more effective epilepsy treatments to bring seizures under control. That said, although more effective antiepileptic drugs (AEDs) have the potential to limit the impact of uncontrolled seizures on cognitive and behavioural function, recently it has been acknowledged that deficits in these functions may be caused by AEDs themselves. The cognitive and behavioural effects of older-generation AEDs have been determined largely from AE reporting rather than from specific assessment. Recently, clinical trials of newer-generation AEDs, such as topiramate, levetiracetam and perampanel, have included standardised neuropsychological tests as outcome measures to assess their impact on cognition and behaviour in children and adolescents. However, to understand how we may limit the cognitive and behavioural side effects of AEDs, it is necessary for us to gain a fuller, more accurate, characterisation of their true impact. Such insight will depend on sophisticated and standardised approaches to the design of AED clinical trials. This review provides a general overview of our current understanding of the impact of both epilepsy and AEDs on cognition and behaviour, before focusing on the AEDs for which more detailed assessment, using standardised cognitive and behavioural measures, has been undertaken. We will then go on to discuss the key elements in the design of future AED clinical trials to address current unmet needs.

  11. Antiepileptic drug-induced bone loss in young male patients who have seizures.

    Science.gov (United States)

    Andress, Dennis L; Ozuna, Judy; Tirschwell, David; Grande, Lucinda; Johnson, Meshell; Jacobson, Arnold F; Spain, William

    2002-05-01

    Long-term antiepileptic drug (AED) therapy is a known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures. To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs. We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time. Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment. Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs.

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

    Science.gov (United States)

    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. Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.

    Science.gov (United States)

    Simó, Marta; Velasco, Roser; Graus, Francesc; Verger, Eugenia; Gil, Miguel; Pineda, Estela; Blasco, Jaume; Bruna, Jordi

    2012-07-01

    Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.

  14. Meta-analyses of newer antiepileptic drugs as adjunct for treatment of focal epilepsy in children.

    Science.gov (United States)

    Mohd-Tahir, Nurul-Ain; Li, Shu-Chuen

    2018-01-01

    This study conducted a systematic review evaluating the effectiveness of newer antiepileptic drugs (AEDs) (namely, lamotrigine, levetiracetam, topiramate, vigabatrin, zonisamide, oxcarbazepine, perampanel, gabapentin, and stiripentol) as add-on for treatment of focal epilepsy in children. Articles were retrieved from EMBASE, Medline and Cochrane Library from inception to January 2016. Treatment outcomes were analysed based on responder, seizure-free, withdrawal and adverse event rates. Quality of each study was also assessed. Twelve articles fulfilled the inclusion criteria. Heterogeneity and quality of the included studies were considered acceptable. Overall, newer AEDs as adjunct therapy in children with inadequate control of focal seizure showed a trend of better seizure outcomes. The pooled ORs for responder, seizure-free and withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69 (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively higher than placebo (OR:1.64, 95%CI:1.13, 2.39). In our updated review, newer AEDs as adjunct therapy for focal epilepsy in children have trends of better effectiveness compared to placebo. Newer AEDs are associated with statistically more children with >50% seizure reduction, and a trend of better seizure freedom. Their tolerability would also be considered acceptable with the observed low withdrawal rate. However, the relative lack of well-conducted RCTs evaluating their effectiveness against other active AED treatment in children would not facilitate evidence-based practice. This highlights the knowledge gap and the need for more well-conducted RCTs against active treatments to ascertain the long term effectiveness and the role of newer AEDs in managing epilepsy in children. Copyright © 2017. Published by Elsevier B.V.

  15. 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.

  16. 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.

  17. 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.

  18. Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

    Directory of Open Access Journals (Sweden)

    Petersen I

    2017-02-01

    Full Text Available Irene Petersen,1,2 Shuk-Li Collings,1,3 Rachel L McCrea,1 Irwin Nazareth,1 David P Osborn,4 Phil J Cowen,5 Cormac J Sammon1 1Department of Primary Care and Population Health, University College London, London, UK; 2Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark; 3OXON Epidemiology, London, UK; 4Division of Psychiatry, University College London, London, UK; 5University Department of Psychiatry, Warneford Hospital, Oxford, UK Objective: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED treatment in pregnancy.Patients and methods: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment.Results: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6% women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to

  19. 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

  20. 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

  1. Cognitive Effects Of Anti-Epileptic Drugs In Nigerians With Epilepsy ...

    African Journals Online (AJOL)

    ... the Neurology Clinic of the University Teaching Hospital, Benin City, Nigeria. Anti-epileptic treatment with either carbamazepine (19 patients), phenytoin (18 patients), or phenobarbitone (18 patients) which was randomly assigned constituted the interventional measure. Cognitive testing, using the Iron Psychology (FePsy) ...

  2. Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a functional multineuron calcium imaging study.

    Science.gov (United States)

    Hongo, Yoshie; Takasu, Keiko; Ikegaya, Yuji; Hasegawa, Minoru; Sakaguchi, Gaku; Ogawa, Koichi

    2015-07-01

    Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg(2+) -free conditions. Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca(2+) influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline-induced synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca(2+) influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca(2+) influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca(2+) influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. 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

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

    Science.gov (United States)

    Joshi, Neelam Hasmukhbhai; Deshpande, Anshula Neeraj; Deshpande, Neeraj Chandrahas; Rathore, Ashutosh Singh

    2017-01-01

    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. 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. 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 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.

  5. 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.

  6. Compelled commercial speech: the Food and Drug Administration's effort to smoke out the tobacco industry through graphic warning labels.

    Science.gov (United States)

    Haynes, Bryan M; Andrews, Anne Hampton; Jacob, C Reade

    2013-01-01

    FDA's proposed graphic warning labels for cigarette packages have been scrutinized for potentially violating the First Amendment's free speech clause. This article addresses the distinction between the commercial speech and compelled speech doctrines and their applicability in analyzing the constitutionality of the labels. The government's position is that the labels evoke an emotional response and educate consumers, while tobacco companies argue that the labels forcibly promote the government's message. Two federal appellate courts, applying different legal standards, have arrived at different conclusions. This article advocates that the Supreme Court, if faced with review of the labels, should apply strict scrutiny and declare the labels unconstitutional.

  7. 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.

  8. USE OF THE NEW ANTIEPILEPTIC DRUG PERAMPANEL (FYCOMPA IN THE TREATMENT OF EPILEPSY: A REVIEW OF FOREIGN LITERATURE

    Directory of Open Access Journals (Sweden)

    O. A. Pylaeva

    2014-01-01

    Full Text Available Despite a considerable advance made in epileptology, resistant epilepsies are about 30% among all epilepsy types particularly in patients with focal seizures. In these cases, there is hope for the success of neurosurgical treatment and the synthesis of new antiepileptic drugs (AEDs. The authors provide a review of the literature dealing the new AED perampanel (Fycompa and consider its mechanism of action, pharmacokinetics, clinical and postmarketing trials of its efficacy, tolerability, and safety. Based on the data available in the literature, it may be concluded that parampanel is a promising highly effective and well tolerated AED to treat partial and secondary generalized seizures.

  9. 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.

  10. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy.

    NARCIS (Netherlands)

    E.B. Samren (Bettina); C.M. van Duijn (Cornelia); S. Koch; V.K. Hiilesma; H. Klepel; A.H. Bardy; B. Mannegetta; A.W. Deichl; E. Gaily; M.L. Granstrom; H. Meinardi; D.E. Grobbee (Diederick); D. Lindhout (Dick); A. Hofman (Albert)

    1997-01-01

    textabstractPURPOSE: To quantify the risks of intrauterine antiepileptic drug (AED) exposure in monotherapy and polytherapy. METHODS: Data from five prospective European studies totaling 1,379 children were pooled and reanalyzed. Data were available for 1,221 children exposed to AED during pregnancy

  11. Intestinal absorption of the antiepileptic drug substance vigabatrin in Göttingen mini-pigs is unaffected by co-administration of amino acids

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Holm, René; Thale, Zia Irene

    2014-01-01

    The anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro evidence suggests that vigabatrin is transported via the proton coupled amino acid transporter (PAT1). The aim of the present study was to investigate whether the intestinal absorption of vigabatrin in vivo...

  12. 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.

  13. Evaluation of Brain Pharmacokinetic and Neuropharmacodynamic Attributes of an Antiepileptic Drug, Lacosamide, in Hepatic and Renal Impairment: Preclinical Evidence.

    Science.gov (United States)

    Kumar, Baldeep; Modi, Manish; Saikia, Biman; Medhi, Bikash

    2017-07-19

    The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered a single dose of lacosamide. At different time points, maximal electroshock (MES) seizure recordings were made followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements. Our results showed a significant increase in the area under the curve of lacosamide in hepatic and renal impairment groups. Reduced clearance of lacosamide was observed in animals with renal impairment. Along with pharmacokinetic alterations, the changes in pharmacodynamic effects of lacosamide were also observed in all the groups. Lacosamide showed a significant protection against MES-induced seizures, oxidative stress, and neuroinflammatory cytokines. These findings revealed that experimentally induced hepatic or renal impairment could alter the pharmacokinetic as well as pharmacodynamic properties of lacosamide. Hence, these conditions may affect the safety and efficacy of lacosamide.

  14. THE PROBLEMS ASSOCIATED WITH SWITCHING BRAND-NAME ANTIEPILEPTIC DRUGS TO GENERICS: A FOCUS ON TOPAMAX: A REVIEW OF LITERATURE AND A CASE REPORT

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2016-01-01

    Full Text Available Despite the rather high efficiency of treatment for epilepsy (overall, 65–70 % of patients can achieve remission or show a considerable decrease in the frequency of seizures, there remains a challenge due to the need to use antiepileptic drugs long and regularly: therapy adherence, compliance, treatment tolerability, and impact of therapy on quality of patent’s life. One of the aspects of this problem is a very common tendency to switch brand-name antiepileptic drugs to their generics that are 1ess expensive, but also less predictably effective and tolerable. The authors review the literature on the interchangeability of brand-name and generic drugs and describe their case. 

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

    Science.gov (United States)

    Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

    2016-05-01

    Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

  17. Antiepileptic drug-related adverse reactions and factors influencing these reactions.

    Science.gov (United States)

    Karimzadeh, Parvaneh; Bakrani, Vahid

    2013-01-01

    According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. In this descriptive study, children less than 14 years old with AED side effects referred to the Children's Medical Center and Mofid Childeren's Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions.

  18. Multiple anti-epileptic drug use in children with epilepsy in Mulago hospital, Uganda: a cross sectional study.

    Science.gov (United States)

    Atugonza, Rita; Kakooza-Mwesige, Angelina; Lhatoo, Samden; Kaddumukasa, Mark; Mugenyi, Levicatus; Sajatovic, Martha; Katabira, Elly; Idro, Richard

    2016-03-09

    Seizures in up to one third of children with epilepsy may not be controlled by the first anti-epileptic drug (AED). In this study, we describe multiple AED usage in children attending a referral clinic in Uganda, the factors associated with multiple AED use and seizure control in affected patients. One hundred thirty nine patients attending Mulago hospital paediatric neurology clinic with epilepsy and who had been on AEDs for ≥6 months were consecutively enrolled from July to December 2013 to reach the calculated sample size. With consent, the history and physical examination were repeated and the neurophysiologic and imaging features obtained from records. Venous blood was also drawn to determine AED drug levels. We determined the proportion of children on multiple AEDs and performed regression analyses to determine factors independently associated with multiple AED use. Forty five out of 139 (32.4 %) children; 46.7 % female, median age 6 (IQR = 3-9) years were on multiple AEDs. The most common combination was sodium valproate and carbamazepine. We found that 59.7 % of children had sub-therapeutic drug levels including 42.2 % of those on multi-therapy. Sub-optimal seizure control (adjusted odds ratio [OR(a)] 3.93, 95 % CI 1.66-9.31, p = 0.002) and presence of focal neurological deficits (OR(a) 3.86, 95 % CI 1.31-11.48, p = 0.014) were independently associated with multiple AED use but not age of seizure onset, duration of epilepsy symptoms, seizure type or history of status epilepticus. One third of children with epilepsy in Mulago receive multiple AEDs. Multiple AED use is most frequent in symptomatic focal epilepsies but doses are frequently sub-optimal. There is urgent need to improve clinical monitoring in our patients.

  19. 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.

  20. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study.

    Science.gov (United States)

    Chen, Y J; Kang, W M; So, W C

    1996-01-01

    Using a randomized parallel group study design, we compared the cognit ive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P 300) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P 300 amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.

  1. Adverse effects of prenatal and early postnatal exposure to antiepileptic drugs: Validation from clinical and basic researches.

    Science.gov (United States)

    Fujimura, Kimino; Mitsuhashi, Takayuki; Takahashi, Takao

    2017-09-01

    Epilepsy requires the long-term administration of antiepileptic drugs (AEDs), and thus, we must consider the effects of prenatal AED exposure on fetus when treating female patients of child bearing age. Large prospective clinical researches in humans have demonstrated the following: (1) prenatal exposure to valproic acid (VPA), carbamazepine, and phenobarbital increases the risk of congenital malformations in a dose-dependent manner and (2) prenatal exposure to VPA increases the risk of higher brain function impairments including intellectual disabilities and autistic spectrum disorders in the offspring. Furthermore, basic researches in animals have shown that prenatal exposure to specific AEDs causes microscopic structural abnormalities in the fetal brain. Specifically, prenatal exposure to VPA has been reported to inhibit the differentiation of neural progenitor cells during the early to middle phases of neuronogenesis, leading to increased number of projection neurons in the superficial layers of postnatal neocortices in mice. It is indispensable to prescribe AEDs that are associated with lower risk of congenital malformations and impairment of higher brain functions as well as to administer them at requisite minimum doses. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy.

    Science.gov (United States)

    Xiaotian, Xu; Hengzhong, Zhang; Yao, Xu; Zhipan, Zhao; Daoliang, Xu; Yumei, Wu

    2013-11-01

    The effects of the antiepileptic drugs sodium valproate (VPA) and levetiracetam (LEV) on reproductive endocrine function, sexual function, and spermatozoa were explored, together with their possible etiological mechanisms, in Chinese Han men with epilepsy. Following VPA treatment (n=32), luteinizing hormone and follicle-stimulating hormone levels were significantly lower than in controls (n=30). The bioactive testosterone/luteinizing hormone ratio and the prolactin level were significantly elevated in the VPA treatment group. There were no significant differences in these hormones between the LEV treatment (n=20) and control groups. The rates of sperm morphologic abnormality (head, body, and tail) were significantly higher in the VPA treatment group than the control group but did not differ significantly between the LEV treatment and control groups. The sperm motility rate was significantly lower in the VPA treatment group (grade A sperm motility rate sperm motility rate sperm motility rate Function Scale than controls, but no significant difference on questions 4 or 5. The total International Index of Erectile Function Scale scores were significantly lower in the VPA and LEV treatment groups. We conclude that treatment with VPA adversely affects reproductive endocrine function, sperm parameters and sexual function to varying degrees in Chinese men with epilepsy. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  3. Antiepileptic drugs: A consideration of clinical and biochemical outcome in patients with epilepsy

    Directory of Open Access Journals (Sweden)

    Zahra Tolou-Ghamari

    2013-01-01

    Conclusions: In Iranian epileptic population, effectiveness of treatment should be attributed by the close supervising of AEDs in relation to clinical circumstance, laboratory data, and therapeutic drug monitoring. Any significant change in patients′ biochemical and hematological data may require close verifying for the rapid detection of severe anemia, leukopenia, lymphocytosis, osteomalacia, or liver failure.

  4. 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...... a potential role for retigabine in the treatment of mania and possibly in the management of bipolar disorder....

  5. Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2014-01-01

    Full Text Available Background: Oxidative stress has been implicated in various disorders including epilepsy. We studied the antioxidant status in patients with epilepsy and aimed at determining whether there was any difference in the antioxidant levels between patients and controls, patients who are not on antiepileptic drugs (AEDs, and on treatment, between individual AEDs and patients on monotherapy and polytherapy. Materials and Methods: Antioxidant levels like catalase, glutathione peroxidase (GPx, vitamin E, glutathione (GSH, thiol group (SH, uric acid, and total antioxidant capacity (TAC were compared between 100 patients with epilepsy and equal number of controls. Twenty-five patients who were not on AEDs were compared with patients on AEDs and the control group. Patients were divided into monotherapy and polytherapy group and antioxidant status was compared between the two groups and between individual drugs. Results: Catalase, SH, vitamin E, and TAC were significantly low in patients with epilepsy than those in the control group (P < 0.001. GSH and uric acid did not show any difference; GPx in patients was significantly higher than those in the control group There were no differences in the antioxidant levels between the treated and the untreated groups; however, it was lower in untreated patients than controls (P < 0.001, suggesting that AEDs do not modify the oxidative stress. Patients on Valproate (VPA showed higher catalase and GPx levels. Catalase was higher in the monotherapy than polytherapy group (P < 0.04. Conclusion: Our study found significantly low levels of antioxidant in patients as compared to controls. AED did not influence the antioxidant status suggesting that seizures induce oxidative stress.

  6. 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.

  7. 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.

  8. Antiepileptic drug use among women from the Taiwanese Registry of Epilepsy and Pregnancy: Obstetric complications and fetal malformation outcomes.

    Directory of Open Access Journals (Sweden)

    Chang Ching Yeh

    Full Text Available To investigate antiepileptic drugs (AEDs prescription and pregnancy outcomes in pregnancies with epilepsy in Taiwan between 2004 and 2015. We retrospectively reviewed data from the Taiwanese Registry of Epilepsy and Pregnancy (TREP. The TREP registry is a voluntary prospective cohort registry, which tracks pregnant women with epilepsy and AED prescription throughout pregnancy, delivery, and early childhood development. All TREP pregnancies (n = 318 that had completed questionnaires up until delivery or had had an unsuccessful pregnancy were analyzed. Over 94.7% of women had been prescribed AEDs during pregnancy, with 69.0% and 25.7% having received monotherapy, or polytherapy, respectively. Among live births, 12 (3.9% reported malformation. Cesarean section rate was reported higher than usual (54.5%. In 2004, 73.3% of AEDs prescribed were 1st generation, with 1st generation prescription rates falling to only 8.3% of total prescribed in 2015. AED polytherapy also fell during the study period (40.0% to 20.0%. Cesarean sections were found to be higher for women over 35 years, who had generalized epilepsy, or had experienced an obstetric complication during pregnancy term. Binary logistic regression revealed that Cesarean section was associated with maternal complications (OR = 5.11, CI 95% = 1.11-23.51, p = 0.036, while malformations were associated with obstetric complication (OR = 20.46, CI 95% = 4.80-87.21, p<0.001. Both AED risk types were not associated with complications or malformations. Our sample provides a unique insight into the women with epilepsy with AED use during pregnancy. Cesarean section rate was observed to be higher than usual, but malformation rates remained low. Results indicate a decrease in both 1st generation AEDs and proportion of patients receiving polytherapy over the study period. Obstetric complications were associated with Cesarean section. Fetal malformations were significantly associated with obstetric

  9. Antiepileptic drug use among women from the Taiwanese Registry of Epilepsy and Pregnancy: Obstetric complications and fetal malformation outcomes.

    Science.gov (United States)

    Yeh, Chang Ching; Lussier, Eric C; Sun, Yi-Ting; Lan, Tzuo-Yun; Yu, Hsiang-Yu; Chang, Tung-Yao

    2017-01-01

    To investigate antiepileptic drugs (AEDs) prescription and pregnancy outcomes in pregnancies with epilepsy in Taiwan between 2004 and 2015. We retrospectively reviewed data from the Taiwanese Registry of Epilepsy and Pregnancy (TREP). The TREP registry is a voluntary prospective cohort registry, which tracks pregnant women with epilepsy and AED prescription throughout pregnancy, delivery, and early childhood development. All TREP pregnancies (n = 318) that had completed questionnaires up until delivery or had had an unsuccessful pregnancy were analyzed. Over 94.7% of women had been prescribed AEDs during pregnancy, with 69.0% and 25.7% having received monotherapy, or polytherapy, respectively. Among live births, 12 (3.9%) reported malformation. Cesarean section rate was reported higher than usual (54.5%). In 2004, 73.3% of AEDs prescribed were 1st generation, with 1st generation prescription rates falling to only 8.3% of total prescribed in 2015. AED polytherapy also fell during the study period (40.0% to 20.0%). Cesarean sections were found to be higher for women over 35 years, who had generalized epilepsy, or had experienced an obstetric complication during pregnancy term. Binary logistic regression revealed that Cesarean section was associated with maternal complications (OR = 5.11, CI 95% = 1.11-23.51, p = 0.036), while malformations were associated with obstetric complication (OR = 20.46, CI 95% = 4.80-87.21, pObstetric complications were associated with Cesarean section. Fetal malformations were significantly associated with obstetric complications. AED risk factors were not significantly associated with either complications or malformations.

  10. The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs.

    Science.gov (United States)

    Frey, Noel; Bodmer, Michael; Bircher, Andreas; Rüegg, Stephan; Jick, Susan S; Meier, Christoph R; Spoendlin, Julia

    2017-12-01

    Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score. We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89-∞), phenytoin (OR 49.96, 95% CI 10.13-∞), and lamotrigine (OR 26.90, 95% CI 4.88-∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307). The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy.

    Directory of Open Access Journals (Sweden)

    Rowena M A Packer

    Full Text Available The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs' owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures, not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy.

  12. 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...

  13. 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

  14. Profilaxis con drogas antiepilépticas en enfermedades neurológicas Prophylactic treatment with antiepileptic drugs in neurological conditions

    Directory of Open Access Journals (Sweden)

    Luciano A. Sposato

    2011-02-01

    Full Text Available El uso profiláctico de drogas antiepilépticas en enfermedades neurológicas como el accidente cerebrovascular isquémico y hemorrágico, la hemorragia subaracnoidea, el traumatismo de cráneo y los tumores cerebrales ha sido motivo de controversia durante muchos años. Estas drogas son indicadas con el fin de disminuir el daño neurológico secundario a las crisis epilépticas. Sin embargo, la escasa evidencia científica disponible para avalar esta hipótesis, las potenciales interacciones farmacológicas, los efectos adversos y algunos informes sobre neurotoxicidad generan dudas en cuanto a esta conducta terapéutica. En esta revisión, analizamos la evidencia acerca del uso profiláctico de drogas epilépticas en las enfermedades neurológicas arriba mencionadas.Prophylactic use of antiepileptic drugs in neurological conditions such as ischemic and hemorrhagic stroke, subarachnoid hemorrhage, head injury, and brain tumors has been matter of debate for many years. These drugs are used for reducing secondary neurological damage caused by epileptic seizures. However, the evidence supporting this indication is scarce. Potential drug interactions, side effects, and even neurotoxicity related to these drugs have raised concern about this therapeutic approach. In this review, we examine the evidence on the prophylactic use of antiepileptic drugs in the neurological disorders above mentioned.

  15. 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

  16. 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.

  17. 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

  18. Compelling Research Opportunities using Isotopes

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-04-23

    Isotopes are vital to the science and technology base of the US economy. Isotopes, both stable and radioactive, are essential tools in the growing science, technology, engineering, and health enterprises of the 21st century. The scientific discoveries and associated advances made as a result of the availability of isotopes today span widely from medicine to biology, physics, chemistry, and a broad range of applications in environmental and material sciences. Isotope issues have become crucial aspects of homeland security. Isotopes are utilized in new resource development, in energy from bio-fuels, petrochemical and nuclear fuels, in drug discovery, health care therapies and diagnostics, in nutrition, in agriculture, and in many other areas. The development and production of isotope products unavailable or difficult to get commercially have been most recently the responsibility of the Department of Energy's Nuclear Energy program. The President's FY09 Budget request proposed the transfer of the Isotope Production program to the Department of Energy's Office of Science in Nuclear Physics and to rename it the National Isotope Production and Application program (NIPA). The transfer has now taken place with the signing of the 2009 appropriations bill. In preparation for this, the Nuclear Science Advisory Committee (NSAC) was requested to establish a standing subcommittee, the NSAC Isotope Subcommittee (NSACI), to advise the DOE Office of Nuclear Physics. The request came in the form of two charges: one, on setting research priorities in the short term for the most compelling opportunities from the vast array of disciplines that develop and use isotopes and two, on making a long term strategic plan for the NIPA program. This is the final report to address charge 1. NSACI membership is comprised of experts from the diverse research communities, industry, production, and homeland security. NSACI discussed research opportunities divided into three areas: (1

  19. Antiepileptic drugs toxicity: A case of toxic epidermal necrolysis in patient with phenytoin prophylaxis post-cranial radiation for brain metastases.

    Science.gov (United States)

    AlQuliti, Khalid; Ratrout, Basem; AlZaki, Alaa

    2014-09-01

    Treatment of epilepsy with antiepileptic drugs (AED) is effective and remains the principal mode of management. A group of adverse effects and drug toxicity can develop immediately or later in the course of treatment. AEDs also have the potential of precipitating idiosyncratic adverse effects including serious cutaneous, hematological and hepatic events. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions are related to or caused by a variety of medications including AEDs, they carry a high mortality and morbidity rate, accurate diagnosis and rapid treatment may improve the prognosis. To characterize the clinical features and methods of differentiating Stevens-Johnson syndrome from toxic epidermal necrolysis using a case study and to identify other factors that may contribute to this critical illness. Clinical knowledge of potential sever adverse reaction of AEDs is essential and may overcome treatment failure with major impact on health-related quality of life in people with epilepsy.

  20. 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, J. B.; Abildstrom, S. Z.; Erdal, Jesper

    2011-01-01

    Purpose 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). Methods A cohort consisting of the Danish...... population was followed from January 1997 to December 2006. The risk of MI, stroke, cardiovascular death, and all-cause death associated with epilepsy was estimated by multivariable Cox proportional hazard models stratified for occurrence of previous stroke. AED use was determined at baseline, and risks...... associated with exposure to individual AEDs were examined in patients with epilepsy. Results In patients without previous stroke, AED-treated epilepsy was associated with an increased risk of MI (hazard ratio [HR], 1.09; 95%CI, 1.00-1.19), stroke (HR, 2.22; 95%CI, 2.09-2.36), cardiovascular death (HR, 1...

  1. A systematic review of placebo-controlled trials of topiramate: How useful is a multiple-indications review for evaluating the adverse events of an antiepileptic drug?

    Science.gov (United States)

    Donegan, Sarah; Dixon, Peter; Hemming, Karla; Tudur-Smith, Catrin; Marson, Anthony

    2015-12-01

    Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by data from trials in other indications. Combining data across trials and indications is a novel method for evaluating AEs. We conducted a multiple-indications review by systematically reviewing randomized placebo-controlled trials of TPM, to compare the nervous system AEs of TPM in epilepsy with those in other indications. Randomized placebo-controlled trials of TPM including patients with any indication were included. We searched Cochrane Central Register of Controlled Trials (Issue 2, 2012) and MEDLINE (1966-February 2012). Two authors assessed eligibility and risk of bias, and extracted data. For each reported nervous system AE, we extracted event rates, applied random-effects inverse-variance meta-analysis (pooling within-indications then across-indications), and assessed within- and across-indication heterogeneity. Ninety trials, including 16 epilepsy trials, were included. A difference was detected between TPM and placebo for three events (i.e., drooling, dysgeusia, and hypoesthesia) that were not reported in epilepsy trials but were reported by other trials. A difference between TPM and placebo was detected for speech disorder using epilepsy trials but not when combining all trials. For two events (i.e., cognitive disorder and "language problems"), no difference was detected between TPM and placebo when using epilepsy trials alone, but a difference was identified using all trials. A difference was detected between TPM and placebo for six events (i.e., ataxia, disturbance in attention, dizziness, memory impairment, paraesthesia, and somnolence) when using epilepsy trials alone, and using all trials. Including trials of any indication enabled detection of differences that would have been missed using epilepsy trials alone. Multiple-indications reviews can improve the synthesis of AEs for

  2. [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.

  3. 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.

  4. Abortion and compelled physician speech.

    Science.gov (United States)

    Orentlicher, David

    2015-01-01

    Informed consent mandates for abortion providers may infringe the First Amendment's freedom of speech. On the other hand, they may reinforce the physician's duty to obtain informed consent. Courts can promote both doctrines by ensuring that compelled physician speech pertains to medical facts about abortion rather than abortion ideology and that compelled speech is truthful and not misleading. © 2015 American Society of Law, Medicine & Ethics, Inc.

  5. In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2

    Directory of Open Access Journals (Sweden)

    Gurpreet Kaur Grewal

    2017-09-01

    Full Text Available ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, we investigated the effect of six antiepileptic drugs (AEDs viz. phenytoin, carbamazepine, valproate, lamotrigine, topiramate and levetiracetam, on the expression and function of ABCB1, ABCC1, ABCC2 and ABCG2 in Caco2 and HepG2 cell lines through real time PCR, western blot and functional activity assays. Further, the interaction of AEDs with maximally induced ABCC2 was studied. Carbamazepine caused a significant induction in expression of ABCB1 and ABCC2 in HepG2 and Caco2 cells, both at the transcript and protein level, together with increased functional activity. Valproate caused a significant increase in the expression and functional activity of ABCB1 in HepG2 only. No significant effect of phenytoin, lamotrigine, topiramate and levetiracetam on the transporters under study was observed in either of the cell lines. We demonstrated the interaction of carbamazepine and valproate with ABCC2 with ATPase and 5,6-carboxyfluorescein inhibition assays. Thus, altered functionality of ABCB1 and ABCC2 can affect the disposition and bioavailability of administered drugs, interfering with AED therapy.

  6. Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy.

    Science.gov (United States)

    Packer, Rowena M A; De Risio, Luisa; Volk, Holger A

    2017-04-07

    Behavioural changes associated with idiopathic epilepsy (IE) have been identified in dogs, with fear and anxiety-related problems seen in both drug-naïve dogs and dogs treated with anti-epileptic drugs (AEDs). Treating anxiety-related behaviour in dogs with IE may be challenging, as seizures are a contraindication for many conventional anxiolytic drugs. In addition, many dogs with IE are already treated with AEDs to reduce their seizure frequency, which may have negative effects if used in polytherapy. Imepitoin is low-affinity partial agonist at the benzodiazepine (BDZ) site of the GABA A receptor, and has been demonstrated to have both anticonvulsant and anxiolytic effects in laboratory rodents. Imepitoin has been developed for the treatment of IE in dogs, with demonstrated anticonvulsant effects and high tolerability and safety. To date, imepitoin's potential to reduce anxiety in dogs with IE has not been investigated. An online survey was conducted to investigate the effect of imepitoin on fear and anxiety-related behaviours in dogs with IE. Eighty-five valid responses were received from owners of dogs with IE currently treated with imepitoin. Anxiety-related behaviour was quantified before and during imepitoin treatment using a validated questionnaire tool (C-BARQ). No differences were observed in the five fear/anxiety-related measures between the two time periods (before vs. during treatment) for dog directed fear, stranger directed fear, non-social fear, pain sensitivity and separation related behaviour. A median 45% reduction in seizure frequency/month was observed following imepitoin treatment; however, imepitoin did not appear effective in reducing seizure frequency in a minority of cases. Polyphagia was the most common chronic side effect, and more side effects were reported in polytherapy cases. Imepitoin does not appear to improve anxiety-related behaviour in dogs with IE treated with this medication for its anti-epileptic effects. Investigating the

  7. Teratogenicity and fetotoxicity of the antiepileptics

    Directory of Open Access Journals (Sweden)

    Nikolić Predrag

    2011-01-01

    Full Text Available Pregnant women with epilepsy have more problems in maintenance of pregnancy and are under higher risk of spontaneous abort ion or occurrence of congenital fetal malformations. Use of antiepileptic drugs during pregnancy is also related to higher risk of congenital fetal malformations. The aim of our study was to determine teratogenicity and fetotoxicity of antiepileptics by performing systematic review of relevant papers. Systematic review was performed using PUBMED and Cochrane Database of Systematic Reviews. Original and review papers that relate to teratogenic effects of antiepileptic drugs were included in the analysis. Fourteen studies were found, out of which there were 7 original papers and 7 review papers. The lowest number of participants in a study was 54 and the highest 3607. Studies followed participants from 5 to 9 years. Antiepileptic drugs were used as monotherapy in 2 studies, while other studies examined both mono- and polytherapy. Doses administered varied from 600 mg (carbamazepine, 100-200 mg (lamotrigine and 600-1000 mg (valproate, depending on kind of administration (mono or polytherapy. Among all examined antiepileptic drugs, valproate has shown the highest relation to occurrence of any degree of mental retardation or congenital malformation. Risk of congenital malformations was correlated with administration of higher drug doses and the use of polytherapy. Carbamazepine was shown to be the safest drug to use during pregnancy. Literature data do not confirm teratogenic effects of antiepileptic drugs with certainty. There are not enough studies that compare drug effects in different stages of pregnancy. Limit of presented studies is also lack of information about the degree of epilepsy and eventual comorbidity.

  8. The effects of ABCC2 G1249A polymorphism on the risk of resistance to antiepileptic drugs: a meta-analysis of the literature.

    Science.gov (United States)

    Chen, Pin; Yan, Qing; Xu, Haitao; Lu, Ailin; Zhao, Peng

    2014-02-01

    The G1249A variant of the multidrug resistance-associated protein 2 (ABCC2) gene may be associated with the development of antiepileptic drug (AED) resistance. Although numerous studies have investigated the association between the G1249A variant and the risk of drug resistance in epilepsy, the results of these studies have been inconclusive. To assess the role of G1249A polymorphism in drug resistance in epilepsy, a meta-analysis was performed. We systematically reviewed relevant studies retrieved by the PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the date extracted from the studies to evaluate the strength of association. We also analyzed the heterogeneity and sensitivity of each report and the publication bias of the studies. A total of 6 published studies, involving 2213 patients (1100 patients with drug-resistant epilepsy and 1113 controls with drug-responsive epilepsy) were reviewed in the present meta-analysis. The overall results indicated that the variant genotypes were associated with a significantly decreased risk of AED resistance (AA vs. GG: OR=0.372, 95% CI=0.182-0.762; recessive model: OR=0.399, 95% CI=0.200-0.795) (fixed-effects model). A stratified analysis by ethnicity showed similar findings for Caucasians in an additive model (A vs. G: OR=0.700, 95% CI=0.494-0.992). The meta-analysis suggests that the ABCC2 G1249A polymorphism is significantly associated with a decreased risk of AED resistance. However, further functional investigations are warranted to validate the association.

  9. Modafinil and its metabolites enhance the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

    Science.gov (United States)

    Zolkowska, Dorota; Andres-Mach, Marta; Prisinzano, Thomas E; Baumann, Michael H; Luszczki, Jarogniew J

    2015-07-01

    Seizures occur when the excitability of brain circuits is not sufficiently restrained by inhibitory mechanisms. Although modafinil is reported to reduce GABA-activated currents and extracellular GABA levels in the brain, the drug exerts anticonvulsant effects in animal studies. The aim of this study was to determine the effects of modafinil and its metabolites (sulfone and carboxylic acid) on the anticonvulsant action of four classical antiepileptic drugs (AEDs)-carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA). Anticonvulsant activity was assessed with the maximal electroshock seizure threshold (MEST) test and MES test in mice. Brain concentrations of AEDs were measured to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Intraperitoneal injection of 75 mg kg(-1) of modafinil or its metabolites significantly elevated the threshold for electroconvulsions in mice, whereas 50 mg kg(-1) of each compound enhanced the anticonvulsant activity of CBZ, PHT, and VPA, but not that of PB. A 25-mg kg(-1) dose of modafinil or its sulfone metabolite enhanced anticonvulsant activity of VPA. Modafinil and its metabolites (50 mg kg(-1)) did not alter total brain concentrations of PB and VPA but did elevate CBZ and PHT. Enhancement of anticonvulsant actions of VPA by modafinil in the mouse MES model is a pharmacodynamic effect. Collectively, our data suggest that modafinil may be a safe and beneficial adjunct to the therapeutic effects of AEDs in human patients.

  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. 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

  12. Several new diverse anticonvulsant agents discovered in a virtual screening campaign aimed at novel antiepileptic drugs to treat refractory epilepsy.

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    Di Ianni, Mauricio E; Enrique, Andrea V; Palestro, Pablo H; Gavernet, Luciana; Talevi, Alan; Bruno-Blanch, Luis E

    2012-12-21

    A virtual screening campaign was conducted in order to discover new anticonvulsant drug candidates for the treatment of refractory epilepsy. To this purpose, a topological discriminant function to identify antiMES drugs and a sequential filtering methodology to discriminate P-glycoprotein substrates and nonsubstrates were jointly applied to ZINC 5 and DrugBank databases. The virtual filters combine an ensemble of 2D classifiers and docking simulations. In the light of the results, 10 structurally diverse compounds were acquired and tested in animal models of seizure and the rotorod test. All 10 candidates showed some level of protection against MES test.

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

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    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.

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

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    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.

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

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    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.

  16. Effects of antiepileptic drugs on mRNA levels of BDNF and NT-3 and cell neogenesis in the developing rat brain.

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    Shi, Xiu-Yu; Wang, Ji-Wen; Cui, Hong; Li, Bao-Min; Lei, Ge-Fei; Sun, Ruo-Peng

    2010-03-01

    Epilepsy is a common neurological disorder that occurs more frequently in childhood than in adulthood. Antiepileptic drugs (AEDs) which are used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment or other uncertain injury. However, the exact mechanisms responsible for adverse effects of AEDs in the developing brain are still not clear. In the present study, we investigate the effects of AEDs on mRNA levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), cell neogenesis and mossy fiber sprouting (MFS) in the developing rat brain. Long-term treatment with Phenobarbital (40mg/kg), valproate (100mg/kg) and topiramate (40mg/kg) reduces BDNF and NT-3 mRNA expression in the developing brain, while lamotrigine reduces mRNA expression only at high dose level (80mg/kg). Cell neogenesis only increases in the rats treated with valproate and lamotrigine. And no differences are observed between the control group and the AEDs-treated groups in the Timm scores of the CA3 region and supragranular region. Our findings present some possible mechanisms to explain why different AEDs cause different cognitive impairment.

  17. 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.

  18. The lack of antiepileptic drugs and worsening of seizures among physically handicapped patients with epilepsy during the Great East Japan Earthquake.

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    Kobayashi, Satoru; Endo, Wakaba; Inui, Takehiko; Wakusawa, Keisuke; Tanaka, Soichiro; Onuma, Akira; Haginoya, Kazuhiro

    2016-08-01

    Takuto Rehabilitation Center for Children is located in Sendai, the capital of the Miyagi prefecture, and faces the Pacific Ocean. The tsunami caused by the Great East Japan Earthquake resulted in tremendous damage to this region. Many physically handicapped patients with epilepsy who are treated at our hospital could not obtain medicine. We surveyed patients with epilepsy, using a questionnaire to identify the problems during the acute phase of the Great East Japan Earthquake. After the earthquake, we mailed questionnaires to physically handicapped patients with epilepsy who are treated and prescribed medications at our hospital, or to their parents. A total of 161 respondents completed the questionnaire. Overall, 68.4% of patients had seven days or less of stockpiled medication when the earthquake initially struck, and 28.6% of patients had no medication or almost no medication during the acute phase after the earthquake. Six patients were forced to stop taking their medication and nine patients experienced a worsening of seizures. Most (93.6%) patients stated they require a stockpile of medication for more than seven days: 20months after the earthquake, 76.9% patients a supply of drugs for more than seven days. We suggest that physically handicapped patients with epilepsy are recommended to prepare for natural disasters by stockpiling additional medication. Even if the stock of antiepileptic drugs is sufficient, stress could cause worsening of seizures. Specialized support is required after a disaster among physically handicapped patients with epilepsy. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. 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

  20. 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.

  1. Decreased bone density induced by antiepileptic drugs can cause accelerated orthodontic tooth movement in male Wistar rats.

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    Akhoundi, Mohammad Sadegh Ahmad; Sheikhzadeh, Sedigheh; Mirhashemi, Amirhossein; Ansari, Elahe; Kheirandish, Yasaman; Allaedini, Mozhgan; Dehpour, Ahmadreza

    2018-02-16

    The aim of the present study was to evaluate the effect of the carbamazepine and valproic acid on orthodontic tooth movement in male Wistar rats. Evaluation of tooth movement after 21 days of drugs infusion was carried out by feeler gauge. Bone densitometry on lateral cephalograms was conducted on days 1 and 21. After dissection of the maxillae, histologic parameters were evaluated. Orthodontic tooth movement was accelerated in experimental groups rather than controls. Optical density was significantly increased in these groups. In histologic sections, mesioapical portion of the PDL (Periodontal Ligament) was wider in experimental groups. Also, distoapical portion of the PDL was wider only in valproic acid group. Valproic acid and carbamazepine can decrease the bone density which may induce the accelerated orthodontic tooth movement in rats. Copyright © 2018. Published by Elsevier Masson SAS.

  2. Modelling the risk of visual field loss arising from long-term exposure to the antiepileptic drug vigabatrin: a cross-sectional approach.

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    Wild, John M; Fone, David L; Aljarudi, Saleh; Lawthom, Charlotte; Smith, Philip E M; Newcombe, Robert G; Lewis, Gareth D

    2013-10-01

    The antiepileptic drug vigabatrin has been used widely since 1989, but has only been approved for use in the US since 2009. The risk:benefit of vigabatrin is generally predicated upon an assumed frequency of associated visual field loss (VAVFL) of approximately 31 %. This estimate is based upon relatively short-term usage (up to 4-5 years) and it is essential to determine whether the frequency of VAVFL increases with longer-term usage. The aim of this study was to model, from cross-sectional evidence, over greater ranges of treatment duration and cumulative dose than previously evaluated, the risk (frequency) of VAVFL with increasing exposure to vigabatrin. This was a retrospective cohort study undertaken in a regional hospital epilepsy clinic. The cohort comprised 147 consecutive patients treated with vigabatrin for refractory complex partial (focal) seizures, who had all undergone ophthalmological examination and who had undertaken perimetry, reliably, according to a standard and robust protocol. The visual field plots were evaluated masked to treatment duration and dose. The risk (frequency) of VAVFL with increasing exposure to vigabatrin was modelled, from the cross-sectional evidence, by standard and plateau logistic regression. The cohort comprised 80 females and 67 males (mean age 40.3 years, standard deviation 13.7). The median duration of vigabatrin exposure was 7.9 years (interquartile range 3.6-11.0, range 0.2-16.1 years); 46 patients (31 %) had received vigabatrin for over 10 years. Eighty-seven patients (59 %) exhibited VAVFL; the proportion with VAVFL was higher in males (66 %) than females (54 %). The plateau model for duration and for cumulative dose exhibited a better fit than the standard model (both p risk:benefit for VAVFL with increasing long-term exposure to vigabatrin and the ensuing increased cost:benefit resulting from the necessary additional visual assessments.

  3. 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.

  4. 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.

  5. 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

  6. Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding

    Directory of Open Access Journals (Sweden)

    Luisa Rocha

    2008-06-01

    Full Text Available Luisa RochaPharmacobiology Department, Center for Research and Advanced Studies, Calz, Tenorios, MéxicoAbstract: Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po on pentylenetetrazol (PTZ-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the first clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce significant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both.Keywords: diazepam, gabapentin, vigabatrin, pentylenetetrazol, benzodiazepine receptors

  7. Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma

    Science.gov (United States)

    Killick-Cole, Clare L.; Singleton, William G. B.; Bienemann, Alison S.; Asby, Daniel J.; Wyatt, Marcella J.; Boulter, Lisa J.; Barua, Neil U.

    2017-01-01

    Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting. Subsequently, immunofluorescent staining of neuronal and glial markers was used to determine toxicity in normal rat hippocampal cells. Pre-treatment of cells with sodium valproate enhanced the cytotoxic effects of carboplatin, in three DIPG cell lines tested. These results demonstrate that sodium valproate causes increased histone H3 acetylation indicative of HDAC inhibition, which is inversely correlated with a reduction in cell viability. Cell viability is reduced through an induction of apoptosis in DIPG cells. Sodium valproate potentiates carboplatin cytotoxicity and prompts further work to define the mechanism responsible for the synergy between these two drugs and determine in vivo efficacy. These findings support the use of sodium valproate as an adjuvant treatment for DIPG. PMID:28542253

  8. 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.

  9. Flavonoid compounds as reversing agents of the P-glycoprotein-mediated multidrug resistance: An in vitro evaluation with focus on antiepileptic drugs.

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    Ferreira, Ana; Rodrigues, Márcio; Fortuna, Ana; Falcão, Amílcar; Alves, Gilberto

    2018-01-01

    The pharmacoresistance to antiepileptic drugs (AEDs) remains a major unsolved therapeutic need. The overexpression of multidrug transporters, as the P-glycoprotein (P-gp), at the level of the blood-brain barrier of epileptic patients has been suggested as a key mechanism underlying the refractory epilepsy. Thus, efforts have been made to search for therapeutically useful P-gp inhibitors. Herein, the strategy of flavonoid/AED combined therapy was exploited as a possible approach to overcome the P-gp-mediated pharmacoresistance. For this purpose, several in vitro studies were performed using Madin-Darby canine kidney II (MDCK II) cells and those transfected with the human multidrug resistance-1 (MDR1) gene, overexpressing the P-gp (MDCK-MDR1). Overall, the results showed that baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin, at 200μM, produced a marked increase on the intracellular accumulation of rhodamine 123 in MDCK-MDR1 cells, potentially through inhibiting the P-gp activity. In addition, with the exception of lamotrigine, all other AEDs tested (phenytoin, carbamazepine and oxcarbazepine) and their active metabolites (carbamazepine-10,11-epoxide and licarbazepine) demonstrated to be P-gp substrates. Furthermore, the most promising flavonoids as P-gp inhibitors promoted a significant increase on the intracellular accumulation of the AEDs (excluding lamotrigine) and their active metabolites in MDCK-MDR1 cells, evidencing to be important drug candidates to reverse the AED-resistance. Thus, the co-administration of AEDs with baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin should continue to be explored as adjuvant therapy for refractory epilepsy. List of chemical compounds studied in this article: Baicalein (PubChem CID: 5,281,605); Carbamazepine (PubChem CID: 2554); Carbamazepine 10,11-epoxide (PubChem CID: 2555); (-)-Epigallocatechin gallate (PubChem CID: 65064); Kaempferol (PubChem CID: 5280863

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

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    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

  11. 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.

  12. Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring.

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    Kumar, Shambhu; Ramanujam, Bhargavi; Chandra, P S; Dash, Deepa; Mehta, Santosh; Anubha, Sharma; Appukutan, Renjith; Rana, Manit Kumar; Tripathi, Manjari

    2018-02-01

    Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study. In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207). One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46). Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  13. Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: A phase III post-hoc analysis.

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    Glauser, Tracy; Laurenza, Antonio; Yang, Haichen; Williams, Betsy; Ma, Tony; Fain, Randi

    2016-01-01

    Perampanel is a selective, noncompetitive AMPA receptor antagonist with demonstrated efficacy and tolerability in partial seizures in patients aged ≥ 12 years in Phase III studies. Post-hoc analysis of these studies was conducted to determine the efficacy and tolerability of perampanel based on the number of concomitant antiepileptic drugs (AEDs) at baseline, as well as to examine which baseline characteristics, if any, were predictors of efficacy. Efficacy parameters were based on the number of baseline AEDs, and logistic regression analyses were used to evaluate the association of demographic and baseline clinical factors with probability of ≥ 50% reduction in seizure frequency. Patients on 1 AED at baseline were significantly more likely to have reduced seizure frequency (P<0.02) and improved 50% responder rate (P<0.02) than patients on 3 AEDs at baseline. Secondarily generalized seizures at baseline, unknown etiology, and use of concomitant non-inducer AEDs were also established as positive predictors of efficacy (50% responder rate; P<0.01). Patients with more AEDs at baseline were associated with greater use of inducers (P<0.01), which may result in decreased exposure of perampanel in these patients and lower efficacy. Patients with 1 AED at baseline had a significantly shorter time since diagnosis compared with patients in the 3 (P<0.01) AEDs group, as well as a lower median seizure frequency at baseline compared to patients on 3 AEDs (P<0.05), suggesting that the reduced efficacy of perampanel with 3 AEDs may also be associated with the greater severity of seizures in the patient groups. The incidence of adverse events in perampanel-treated patients was similar regardless of the number of AEDs at baseline. Greater efficacy is predicted for patients receiving fewer concomitant AEDs when starting perampanel, as well as for those receiving concomitant treatment with AEDs that are not CYP3A4 enzyme-inducers, compared to patients treated with multiple

  14. Modification in body weight associated with antiepileptic drugs Alteração de peso corpóreo associado às drogas antiepilépticas

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    Camilla N. De Gaspari

    2010-04-01

    Full Text Available Antiepileptic drugs (AED may cause body weight changes. OBJECTIVE: To evaluate the dietary habits and body weight associated with AED in epileptic patients. METHOD: Sixty-six patients were subjected to two interviews, and had their weight and body mass index calculated and compared at both times, interval between six to eight months. RESULTS: It was observed that 59.1% showed weight gain. The patients who had no weight gain had a greater proportion of individuals who engaged in some form of physical activity. However, of the 45 patients who maintained their initial dietary and medication pattern, 75.6% recorded a weight gain. Weight gain was seen in 66.7% of patients on carbamazepine (n=18, 60% on valproate (n=5, 50% on carbamazepine+clobazam treatment (n=14, and 58.3% of patients on other(s polytherapy (n=12. CONCLUSION: The patient should be alerted to possible weight gain, and should be advised about dieting and participating in regular physical activity.Drogas antiepilépticas (DAE podem causar alteração do peso corpóreo. OBJETIVO: Avaliar o hábito alimentar e do peso corpóreo associado às DAE em pacientes epilépticos. MÉTODO: Sessenta e seis pacientes foram submetidos a duas entrevistas, e tiveram peso e índice de massa corpórea (IMC calculados e comparados nos dois momentos, com intervalo de 6 a 8 meses. RESULTADOS: Apresentaram aumento de peso 59,1% dos pacientes. Porém, os pacientes que não tiveram ganho de peso apresentaram maior proporção de indivíduos desenvolvendo alguma atividade física. Enquanto que dentre os 45 que mantiveram o padrão alimentar e medicação inicial 75,6% registraram ganho de peso. Observou-se ganho de peso em 66,7% dos pacientes com carbamazepina (n=18; 60% com valproato (n=5; 50% com carbamazepina e clobazam (n=14; 58,3% dos pacientes com politerapia (n=12. CONCLUSÃO: Deve-se alertar o paciente sobre o ganho de peso, orientar quanto à dieta alimentar e, principalmente, incentivar atividade f

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

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    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

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

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    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

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

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    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

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

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    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.

  19. Contributing Chemistry and Compelling Physics

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    Editorial

    2013-04-01

    Full Text Available Chemistry as an integral part of biology has been studied and utilised to yield numerous solutions in healthcare. Both the in vivo and in vitro applications of chemically synthesized compounds as drugs and the culture media used for cell culture respectively have been an indispensable tool in therapeutic and research arena in healthcare. The evolving specialty of regenerative medicine has been exploring the physical characteristics of the cell culture environment to see its effect on the behaviour of cells in vitro. For instance, mere change of matrix stiffness gives rise to a cascade of chemical events leading to different biological outputs as reported (1 in which softer matrices induced the mesenchymal stem cells to give rise to neuronal cells and increasing the matrix stiffness made the same stem cells to differentiate into chondrogenic and osteogenic lineages. The regulated movement of ions across membranes have been found to influence cell morphogenesis and stem cell regeneration (2. The influence of variety of media, reagents, growth factors, scaffolds etc. on the different types of cells and the varying needs of each type of cell are being continuously studied with an aim of advancing regenerative medicine based solutions. In this issue, the article by Kazemnejad et al is reporting the role of wnt signalling on menstrual blood derived stem cells (MenSCs by studying the influence of Lithium chloride on the proliferation of these cells. They have come out results that prove that the MenSCs have unique immunophenotyping properties and that Wnt signaling pathway regulates MenSCs proliferation via the trans-localization of activated-ß-catenin protein. Another article by Sharma et al has focussed on the gene expression pathways and on the specific modification or modulation of a key molecular player of homing and engraftment of the hematopoietic progenitor cells which will help in enhancing the efficacy of hematopoietic stem cell

  20. 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

  1. Infantile Spasms and Cytomegalovirus Infection: Antiviral and Antiepileptic Treatment

    Science.gov (United States)

    Dunin-Wasowicz, Dorota; Kasprzyk-Obara, Jolanta; Jurkiewicz, Elzbieta; Kapusta, Monika; Milewska-Bobula, Bogumila

    2007-01-01

    From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before…

  2. New antiepileptic therapies.

    Science.gov (United States)

    Ozuna, J

    1997-04-01

    This is an exciting time for AED development. Four new AEDs have been approved for use in the last 3 years and several more are being evaluated. New formulations of traditional therapies, such as Tegretol XR, and IV and IM fosphenytoin offer alternatives for the management of acute and chronic seizure disorders (see "Clip & Save" and "What's News"). With these new treatments options, providers will be challenged to choose the most appropriate drug or drug combination for their patients based on seizure type, AED mechanisms of action, pharmacokinetic properties, adverse effects, and drug interactions.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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.

  8. Pharmacokinetic and pharmacodynamic interactions between antiepileptics and antidepressants.

    Science.gov (United States)

    Italiano, Domenico; Spina, Edoardo; de Leon, Jose

    2014-11-01

    Antiepileptic-antidepressant combinations are frequently used by clinicians; their pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions (DIs) have not been well studied but are frequently likely to be clinically relevant. This article provides a comprehensive review of PK DIs between antiepileptics and antidepressants. In the absence of PD DI studies, PD information on pharmacological mechanisms and studies on efficacy and safety of individual drugs are reviewed. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone and the inhibitory properties of valproic acid and some antidepressants are well understood; correction factors are provided if appropriate DI studies have been completed. More PK studies are needed for: i) antiepileptics with potent inductive effects for all recently approved antidepressants; ii) high doses of mild CYP3A4 inducers, such as clobazam, eslicarbazepine, oxcarbazepine, rufinamide and topiramate for reboxetine and vilazodone; iii) valproate as a possible inhibitor, mild inducer or both a mild inducer and competitive inhibitor of some antidepressants; and iv) inhibitory effects of long-term fluoxetine use on clobazam, lacosamide, phenobarbital, primidone, carbamazepine, felbamate, tiagabine and zonisamide. Possible synergistic or additive beneficial PD DIs in generalized anxiety disorder, chronic pain, migraine prophylaxis, weight control and menopausal symptoms need study.

  9. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

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    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.

  10. Hypnotic and antiepileptic effects of cannabidiol.

    Science.gov (United States)

    Carlini, E A; Cunha, J M

    1981-01-01

    Clinical trials with cannabidiol (CBD) in healthy volunteers, isomniacs, and epileptic patients conducted in the authors' laboratory from 1972 up to the present are reviewed. Acute doses of cannabidiol ranging from 10 to 600 mg and chronic administration of 10 mg for 20 days or 3 mg/kg/day for 30 days did not induce psychologic or physical symptoms suggestive of psychotropic or toxic effects; however, several volunteers complained of somnolence. Complementary laboratory tests (EKG, blood pressure, and blood and urine analysis) revealed no sign of toxicity. Doses of 40, 80, and 160 mg cannabidiol were compared to placebo and 5 mg nitrazepam in 15 insomniac volunteers. Subjects receiving 160 mg cannabidiol reported having slept significantly more than those receiving placebo; the volunteers also reported significantly less dream recall; with the three doses of cannabidiol than with placebo. Fifteen patients suffering from secondary generalized epilepsy refractory to known antiepileptic drugs received either 200 to 300 mg cannabidiol daily or placebo for as long as 4.5 months. Seven out of the eight epileptics receiving cannabidiol had improvement of their disease state, whereas only one placebo patient improved.

  11. 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

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    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

  12. 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,…

  13. Compulsive gambling possibly associated with antiepileptic medication

    OpenAIRE

    Storrier, Susanne; Beran, Roy G.

    2014-01-01

    Compulsive gambling is recognized with Parkinson's disease treatment with dopamine agonists but has not been reported with antiepileptic medications (AEMs) in epilepsy. This is the first report regarding possible compulsive gambling, provoked by AEMs in a patient with idiopathic generalized epilepsy, who presented with nonconvulsive status epilepticus, having previously not achieved seizure control with carbamazepine, valproate, (VPA), topiramate, gabapentin (GPT), lamotrigine (LTG), and clob...

  14. Compelling Comprehensible Input, Academic Language and School Libraries

    Directory of Open Access Journals (Sweden)

    Stephen Krashen

    2014-11-01

    Full Text Available There is abundant research confirming that we pass through three stages on the path to full development of literacy, which includes the acquisition of academic language. The stages are: hearing stories, doing a great deal of self-selected reading, followed by reading for our own interest in our chosen specialization. At stages two and three, the reading is highly interesting or compelling to the reader. It is also specialized; there is no attempt to cover a wide variety. The research confirms that the library, in particular school library, makes a powerful contribution at all three stages: for many living in poverty it is the only place to find books for recreational reading or specialized interest reading, with the librarian serving as the guide on how to locate information as well as supplier of compelling reading. The expertise of certified librarians is pivotal for compelling reading in a foreign language, such as EFL worldwide and ELLs in the US, as well as compelling reading in children’s heritage languages.

  15. Requirements for generic antiepileptic medicines: a clinical perspective.

    Science.gov (United States)

    Trinka, Eugen; Krämer, Günter; Graf, Martin

    2011-12-01

    Many antiepileptic drugs (AEDs) are now available as a generic product. This can potentially save the healthcare providers massive costs. Hence, governmental authorities have introduced rules and incentives for clinicians to switch from the original branded AED to a generic product. Clinicians and patients with epilepsy are reluctant to switch. The licensing of generic AEDs is based on the equation that bioavailability means therapeutic equivalence. However, from a clinical standpoint one has to consider several other relevant issues: (1) Do generic AEDs have the same efficacy, safety and quality? (2) Can generic AEDs be used as substitutions for brand AEDs? (3) Can generic products of AEDs be used interchangeably? (4) Does the generic AED manufacturer guarantee the long-term consistency of availability on the market? (4) Do generic AEDs reduce the costs, and--if so--are these costs worth any additional risk to patient's safety? This article reviews the clinical issues related to current bioequivalence, prescribability, and switchability of AEDs.

  16. Quantitative EEG findings and response to treatment with antiepileptic medications in children with epilepsy.

    Science.gov (United States)

    Ouyang, Chen-Sen; Chiang, Ching-Tai; Yang, Rei-Cheng; Wu, Rong-Ching; Wu, Hui-Chuan; Lin, Lung-Chang

    2018-01-01

    Epilepsy is a common chronic disorder in pediatric neurology. Nowadays, a variety of antiepileptic drugs (AEDs) are available. A scientific method designed to evaluate the effectiveness of AEDs in the early stage of treatment has not been reported. In this study, we try to use quantitative EEG (QEEG) analysis as a biomarker to evaluate therapeutic effectiveness. 20 epileptic children were enrolled in this study. Participants were classified as effective if they achieved a reduction in seizure frequency over 50%. Ineffective was defined as a reduction in seizure frequency less than 50%. Eleven participants were placed in the effective group, the remaining 9 participants were placed in the ineffective group. EEG segments before and after 1-3months of antiepileptic drugs start/change were analyzed and compared by QEEG analysis. The follow-up EEG segments after the 2nd examinations were used to test the accuracy of the analytic results. Six crucial EEG feature descriptors were selected for classifying the effective and ineffective groups. Significantly increased RelPowAlpha_avg_AVG, RelPowAlpha_snr_AVG, HjorthM_avg_AVG, and DecorrTime_snr_AVG values were found in the effective group as compared to the ineffective group. On the contrary, there were significantly decreases in DecorrTime_std_AVG, and Wavelet_db4_EnergyBand_5_avg_AVG values in the effective group as compared to the ineffective group. The analyses yielded a precision rate of 100%. When the follow-up EEG segments were used to test the analytic results, the accuracy was 83.3%. The developed method is a useful tool in analyzing the effectiveness of antiepileptic drugs. This method may assist pediatric neurologists in evaluating the efficacy of AEDs and making antiepileptic drug adjustments when managing epileptic patients in the early stage. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Decreased efficacy of an etonogestrel implant in a woman on antiepileptic medications: a case report

    OpenAIRE

    Lange, Jill; Teal, Stephanie; Tocce, Kristina

    2014-01-01

    Introduction Many antiepileptic drugs decrease the efficacy of combined hormonal contraceptives due to their inducing effect on cytochrome P450 liver metabolism. Less is known about the pharmacokinetics and outcomes of concomitant use of the etonogestrel implant and hepatic enzyme-inducing medications. Case presentation A 22-year-old Hispanic woman with a long-standing seizure disorder treated with carbamazepine for 9 years became pregnant after 25 months of etonogestrel implant use. Conclusi...

  18. 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.

  19. Compulsive gambling possibly associated with antiepileptic medication

    Directory of Open Access Journals (Sweden)

    Susanne Storrier

    2014-01-01

    Full Text Available Compulsive gambling is recognized with Parkinson's disease treatment with dopamine agonists but has not been reported with antiepileptic medications (AEMs in epilepsy. This is the first report regarding possible compulsive gambling, provoked by AEMs in a patient with idiopathic generalized epilepsy, who presented with nonconvulsive status epilepticus, having previously not achieved seizure control with carbamazepine, valproate, (VPA, topiramate, gabapentin (GPT, lamotrigine (LTG, and clobazam. Levetiracetam (LEV was added to VPA and GPT, which the patient was already taking and LTG subsequently retrialed. Following the reintroduction of LTG, she lost $4000–5000, which she concealed. With better seizure control, VPA and GPT were withdrawn, leaving her on LEV and LTG. With increased LTG dosage, she lost $50,000, prompting discovery of her gambling.

  20. Compulsive gambling possibly associated with antiepileptic medication.

    Science.gov (United States)

    Storrier, Susanne; Beran, Roy G

    2014-01-01

    Compulsive gambling is recognized with Parkinson's disease treatment with dopamine agonists but has not been reported with antiepileptic medications (AEMs) in epilepsy. This is the first report regarding possible compulsive gambling, provoked by AEMs in a patient with idiopathic generalized epilepsy, who presented with nonconvulsive status epilepticus, having previously not achieved seizure control with carbamazepine, valproate, (VPA), topiramate, gabapentin (GPT), lamotrigine (LTG), and clobazam. Levetiracetam (LEV) was added to VPA and GPT, which the patient was already taking and LTG subsequently retrialed. Following the reintroduction of LTG, she lost $4000-5000, which she concealed. With better seizure control, VPA and GPT were withdrawn, leaving her on LEV and LTG. With increased LTG dosage, she lost $50,000, prompting discovery of her gambling.

  1. Decreased efficacy of an etonogestrel implant in a woman on antiepileptic medications: a case report.

    Science.gov (United States)

    Lange, Jill; Teal, Stephanie; Tocce, Kristina

    2014-02-11

    Many antiepileptic drugs decrease the efficacy of combined hormonal contraceptives due to their inducing effect on cytochrome P450 liver metabolism. Less is known about the pharmacokinetics and outcomes of concomitant use of the etonogestrel implant and hepatic enzyme-inducing medications. A 22-year-old Hispanic woman with a long-standing seizure disorder treated with carbamazepine for 9 years became pregnant after 25 months of etonogestrel implant use. Hepatic enzyme-inducing drugs may reduce the efficacy of contraceptive implants. Contraceptive counseling for patients with medical co-morbidities requiring hepatic enzyme-inducing medications should include this information.

  2. Antiepileptic Effects of Lacosamide Loaded Polymers Implanted Subdurally in GAERS

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    Sebastien H. Bauquier

    2016-01-01

    Full Text Available The current experiment investigated the ability of coaxial electrospun poly(D,L-lactide-co-glycolide (PLGA biodegradable polymer implants loaded with the antiepileptic drugs (AED lacosamide to reduce seizures following implantation above the motor cortex in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS. In this prospective, randomized, masked experiments, GAERS underwent surgery for implantation of skull electrodes (n=6, skull electrodes and blank polymers (n=6, or skull electrodes and lacosamide loaded polymers (n=6. Thirty-minute electroencephalogram (EEG recordings were started at day 7 after surgery and continued for eight weeks. The number of SWDs and mean duration of one SWD were compared week-by-week between the three groups. There was no difference in the number of SWDs between any of the groups. However, the mean duration of one SWD was significantly lower in the lacosamide polymer group for up to 7 weeks when compared to the control group (0.004

  3. Clear and compelling evidence: the Polish tribunal on abortion rights.

    Science.gov (United States)

    Girard, Françoise; Nowicka, Wanda

    2002-05-01

    On 25 July 2001 the Polish Federation for Women and Family Planning organised a Tribunal on Abortion Rights in Warsaw, to publicize the negative consequences of the criminalization of abortion in Poland. A panel of Polish and foreign experts heard the testimonials of seven Polish women's experiences under the 1993 "Anti-Abortion Act". Only two of the seven women were able to tell their stories in person. One died in 2001, at the age of 21, of an unsafe abortion. One is legally blind after having carried her last pregnancy to term. One is in prison for infanticide, which in all likelihood was committed by her boyfriend. National and foreign journalists were in attendance, as well as observers from all walks of life--writers, students, mothers, activists, feminists, husbands. The evidence was clear and compelling. Restrictive abortion laws make abortion unsafe by pushing it underground, endanger women's health, create a climate where even those services that are allowed by law-become unavailable, and contravene standards set by international human rights law. The restrictive abortion law in Poland has not increased the number of births; it has only caused women and their families suffering. The Tribunal brought the issue of abortion into the media prior to an election campaign and galvanised Polish and other Eastern European women's groups to become more active in defence of abortion rights.

  4. An industrial approach to design compelling VR and AR experience

    Science.gov (United States)

    Richir, Simon; Fuchs, Philippe; Lourdeaux, Domitile; Buche, Cédric; Querrec, Ronan

    2013-03-01

    The convergence of technologies currently observed in the field of VR, AR, robotics and consumer electronic reinforces the trend of new applications appearing every day. But when transferring knowledge acquired from research to businesses, research laboratories are often at a loss because of a lack of knowledge of the design and integration processes in creating an industrial scale product. In fact, the innovation approaches that take a good idea from the laboratory to a successful industrial product are often little known to researchers. The objective of this paper is to present the results of the work of several research teams that have finalized a working method for researchers and manufacturers that allow them to design virtual or augmented reality systems and enable their users to enjoy "a compelling VR experience". That approach, called "the I2I method", present 11 phases from "Establishing technological and competitive intelligence and industrial property" to "Improvements" through the "Definition of the Behavioral Interface, Virtual Environment and Behavioral Software Assistance". As a result of the experience gained by various research teams, this design approach benefits from contributions from current VR and AR research. Our objective is to validate and continuously move such multidisciplinary design team methods forward.

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Antiepileptic drugs and risk of suicide: a nationwide study

    DEFF Research Database (Denmark)

    Olesen, J.B.; 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...

  10. Smoking cessation: How compelling is the evidence? A review

    DEFF Research Database (Denmark)

    Tønnesen, Philip

    2009-01-01

    with scientific well-documented efficacy when used for 2-3 months and mostly mild side effects. Alternative therapies such as hypnosis and acupuncture have no scientifically proven effects. CONCLUSIONS: With the most optimal drugs and counseling today a 1-year abstinence rate of approximately 25% can be expected...

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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.

    2013-01-01

    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

  14. Drug and poison information - the Tygerberg experience

    African Journals Online (AJOL)

    100. TABLE VI. Pharmacotherapy consultations. Drug categories. Antimicrobial. Cardiovascular. Anti-epileptic. Neuroleptic and anti-histamine. Antidepressant. Benzodiazepines, barbiturates and other sedative hypnotics. Respiratory. Miscellaneous. Total. 1986 - 1988. 1990 - 1991. No. %. No. %. Average (%). 312. 29,1.

  15. Antiepileptic teratogen valproic acid (VPA) modulates organisation and dynamics of the actin cytoskeleton

    DEFF Research Database (Denmark)

    Walmod, P S; Skladchikova, G; Kawa, A

    1999-01-01

    for the VPA mediated inhibition of motility. In addition it is shown that the actomyosin cytoskeleton of VPA-treated cells was capable of contraction upon exposure to ATP, indicating that the reduced motility of VPA-treated cells was not caused by an inhibition of actomyosin contraction. On the other hand...... state. These findings indicate that VPA affects cell morphology and motility through interference with the dynamics of the actin cytoskeleton.......The antiepileptic drug valproic acid (VPA) and teratogenic VPA analogues have been demonstrated to inhibit cell motility and affect cell morphology. We here show that disruption of microtubules or of microfilaments by exposure to nocodazole or cytochalasin D had different effects on morphology...

  16. 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.

  17. Ezogabine: a novel antiepileptic for adjunctive treatment of partial-onset seizures.

    Science.gov (United States)

    Amabile, Celene M; Vasudevan, Arvind

    2013-02-01

    Epilepsy is defined as a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults. It is a disruption of the electrical conductivity or activity in the brain, resulting in a seizure. In the United States, approximately 120 of every 100,000 people seek medical attention due to new seizure activity. Ezogabine, known as retigabine in Europe, is an ethyl N-(2-amino-4-[{fluorophenyl}methlamino]phenylcarbamate). The drug has been approved by the United States Food and Drug Administration (FDA) and European Medicines Agency for adjunctive treatment of partial-onset seizures in adults. Ezogabine exerts its therapeutic effect by enhancing transmembrane potassium channels (KCNQ ion channels), which is a novel mechanism in comparison with other antiepileptics. There are no specific documented contraindications to ezogabine. Warnings target patients that have benign prostatic hyperplasia or are receiving concomitant anticholinergic drugs due to a risk of urinary retention (2%). The FDA has required that ezogabine be part of a risk evaluation and mitigation strategy program in order to inform health care professionals of the risk of urinary retention. Prescribers should inform patients that ezogabine can cause urinary retention, including urinary hesitation, and instruct them to seek immediate medical attention if these symptoms occur. A medication guide has been developed for distribution to patients. © 2013 Pharmacotherapy Publications, Inc.

  18. Compelling Memory: 9/11 and the Work of Mourning in Mike Binder's Reign over Me

    NARCIS (Netherlands)

    Peeren, E.

    2016-01-01

    This article contends that the American commemoration of 9/11 has been dominantly conducted in a compelling, spectacularized manner. The obligation to remember is accompanied by an expectation that this memory will be put on display in the form of emotional expression and/or memory objects.

  19. K-12 School Diversity and Social Cohesion: Evidence in Support of a Compelling State Interest

    Science.gov (United States)

    Mikulyuk, Ashley B.; Braddock, Jomills H.

    2018-01-01

    Despite existing research that demonstrates the benefits of racial diversity in education, the Court has become increasingly disinclined to allow the use of race or ethnicity in education policy targeted to increase race/ethnic diversity, absent a compelling state interest. The debate over the merits of educational diversity has almost exclusively…

  20. Compelling teaching with the four Cs: caring, comedy, creativity, and challenging.

    Science.gov (United States)

    Story, Lachel; Butts, Janie B

    2010-05-01

    The traditional classroom, particularly in nursing, often is stifling to students and teachers. A dynamic co-learning experience creates a potential to move students from merely obtaining knowledge to practice. This article presents an exemplar of the transformative learning process within the nursing education setting. The concepts forming this compelling teaching approach are caring, comedy, creativity, and challenging (the four Cs). Through this innovative teaching method, opportunities are created for authentic co-learning to occur.

  1. Epilepsy as a pyridoxine-dependent condition: quantified urinary biomarkers for status evaluation and monitoring antiepileptic treatment.

    Science.gov (United States)

    Dolina, Svetlana; Margalit, Dov; Malitsky, Sergey; Pressman, Eugeny; Rabinkov, Aharon

    2012-08-01

    The study testifies an assumption on epilepsy as an inborn error of pyridoxine metabolism and suggests non-invasive quantitative biomarkers for clarified evaluation of clinical status and monitoring an individual treatment by antiepileptic drugs. Urinary parameters of pyridoxal-phosphate (PLP)-dependent tryptophan degradation and the level of 4-pyridoxic acid, the end product of pyridoxine metabolism, were measured by HPLC method with simultaneous ultraviolet and fluorimetric detection in children with different forms of epilepsy and matched healthy controls. The concentrations of compounds formed or metabolized in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) along with correlations between them turned out to be quantitative biomarkers useful for both clarifying patient's clinical state and monitoring antiepileptic treatment. In particular, the value of the ratio of 4-pyridoxic acid to kynurenine appears to be an index of an experienced seizure attack, while the ratio of 3-hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase, the enzyme of critical sensitivity to PLP supply. Growing progressively worse, epilepsy is accompanied by aggravation of PLP-dependent disturbances of tryptophan metabolism and expanding inhibition of kynureninase. The affected pyridoxine metabolism is discussed as an inborn genetic trait in epilepsy in general, rather than a specific sign of pyridoxine-dependent epilepsy solely. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.

    Science.gov (United States)

    Rauchenzauner, Markus; Griesmacher, Andrea; Tatarczyk, Tobias; Haberlandt, Edda; Strasak, Alexander; Zimmerhackl, Lothar-Bernd; Falkensammer, Gerda; Luef, Gerhard; Högler, Wolfgang

    2010-03-01

    The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition. Eighty-five children (38 males, 47 females; mean age 12 y 5 mo, SD 3 y 4 mo) were treated with valproate and 40 children (28 males, 12 females; mean age 11 y 10 mo, SD 3 y) were treated with other AEDs (lamotrigine, sulthiame, or oxcarbazepine), comprising the non-valproate group. Forty-one healthy children (29 males 12 females; mean age 12 y 1 mo, SD 3 y 5 mo) served as a comparison group. Height, weight, body impedance analysis, 25-hydroxyvitamin D, calcium, phosphate, two bone resorption markers (receptor activator of nuclear factor kappaB ligand [RANKL] and tartrate-resistant acid phosphatase 5b [TRAP5b]), osteoprotegerin, and leptin were measured. No child was vitamin D deficient as defined by a 25-hydroxyvitamin D (25OHD) level of less than 25 nmol/l (children than in the non-valproate group, as were calcium (p=0.027) and RANKL (p=0.007) concentrations. Similarly, leptin was significantly higher in the valproate group than in control participants (pchildren with epilepsy. Valproate therapy is associated with increases in weight, body fat, and leptin concentration, as well as with a bone metabolic profile that resembles slightly increased parathyroid hormone action.

  3. Prophylactic Antiepileptics and Seizure Incidence Following Subarachnoid Hemorrhage: A Propensity Score-Matched Analysis

    Science.gov (United States)

    Panczykowski, David; Pease, Matthew; Zhao, Yin; Weiner, Gregory; Ares, William; Crago, Elizabeth; Jankowitz, Brian; Ducruet, Andrew F.

    2016-01-01

    Background and Purpose The utility of prophylactic antiepileptic drug (AED) administration following spontaneous subarachnoid hemorrhage (SAH) remains controversial. AEDs have not clearly been associated with a reduction in seizure incidence and have been associated with both neurologic worsening and delayed functional recovery in this setting. Methods We retrospectively analyzed a prospectively collected database of SAH patients admitted to our institution between 2005 and 2010. Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007 no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score-matched analysis was then performed to compare the development of clinical and/or electrographic seizures in these two populations. Results 353 patients with spontaneous SAH were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patients suffered clinical and/or electrographic seizures, most frequently occurring within 24-hrs of ictus (47%). The incidence of seizures did not vary significantly based on the use of prophylactic AEDs (11 vs. 8%, p=0.33). Propensity score-matched analyses suggest that patients receiving prophylactic AEDs had a similar likelihood of suffering seizures as those who did not (p=0.49). Conclusions Propensity score-matched analysis suggests that prophylactic AEDs do not significantly reduce the risk of seizure occurrence in patients with spontaneous SAH. PMID:27301932

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

    OpenAIRE

    Rajput Muhammad Ali; Khan Rafeeq A.; Feroz Zeeshan

    2013-01-01

    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 signif...

  5. Which Design Components of Nutrition Infographics Make Them Memorable and Compelling?

    Science.gov (United States)

    Wansink, Brian; Robbins, Rebecca

    2016-11-01

    Which design features of nutrition infographics make them memorable and compelling? First, we conducted 3 focus groups with a total of 28 participants to understand preferred infographic characteristics of adults who were mostly in their early 20s. Second, using between subject design, a slide show of single-image infographics was displayed to an independent sample of college students and young career university employees (N = 50). We assigned participants randomly to either active or passive processing conditions. We conducted correlation and regression analyses to examine differences in recall and intention by infographic characteristics and processing conditions. Regardless of whether a person was actively or passively viewing the infographics, the most robust predictor of recall was an action-oriented title (p = .003). Surprisingly, infographics in color (vs black-and-white), humorous, or simply worded were no more memorable or effective than if they simply had actionable titles. Action-oriented titles make infographics memorable and compelling. Regardless of how involved a person is in processing an infographic, cartoon, or illustration, time spent on perfecting an action-oriented title will be time better spent than on making the infographic colorful, humorous, or detailed. Whereas content and detail of the infographic are important, effectiveness might be improved by the command given in its title or subtitle.

  6. Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula Assa Foetida Gum on Pentylentetrazole induced Kindling in Male Mice

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2013-11-01

    Full Text Available Introduction: Considering the prevalence of epilepsy and the failure of available treatments for many epileptic patients, finding more effective drugs in the treatment of epilepsy seems necessary. Oxidative stress has a special role in the pathogenesis of epileptic syndrome. Therefore, in the present study, we have examined the anti-epileptic and anti-oxidant properties of the Ferula Assa Foetida gum extract, using the pentylentetrazole (PTZ kindling method. group which received valproate (100 mg/kg as anti-convulsant drug, 4-5 & 6- the groups of kindled mice that pretreated with 25, 50 and 100 mg/kg doses of Ferula Assa Foetida gum extract. Methods: Kindling has been induced in all groups, except for the control group via 11 PTZ injections (35 mg /kg ip every other day for 22 days. In the 24th day, the PTZ challenge dose was injected (75 mg / kg to all groups except the control group. The intensity of seizures were observed and noted until 30 minutes after PTZ injection. At list, the mice were decapitated and the brains of all the mice were removed.. and their biochemical factors levels including malondialdehyde (MDA, superoxide dismutase (SOD and nitric oxide (NO were determined. Results: Results of this study show that Ferula Assa Foetida gum extract is able to reduce seizure duration and its intensity. In addition, this extract has reduced MDA and NO levels and increased the level of SOD in the brain tissue compared to the PTZ- kindled mice. Discussion: It can be concluded that Ferula Assa Foetida gum extract, in specific doses, is able to show an anti-epileptic effect because of its antioxidant properties, probably acting through an enzyme activity mechanism. In this experimental study, sixty male Albino mice weighing 25-30 g were selected and were randomly divided into 6 groups. 1- the control group, 2- PTZ-kindled mice, 3- positive control

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

    OpenAIRE

    Freitas-Lima, Priscila de; Baldoni, Andre de Oliveira; Alexandre, Veriano; Pereira, Leonardo Regis Leira; Sakamoto, Americo Ceiki

    2013-01-01

    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% ...

  8. A Spoonful of (Added) Sugar Helps the Constitution Go Down: Curing the Compelled Speech Commercial Speech Doctrine with FDA’s Added Sugars Rule.

    Science.gov (United States)

    Smith, Colleen

    On May 27, 2016, the Food and Drug Administration (FDA) announced that it was adopting a new rule that requires food manufacturers to list—on the already mandated Nutrition Facts label—how many grams of sugar have been added to a food product. Many opponents have criticized this “added sugars” rule on First Amendment grounds, arguing that the rule violates the commercial speech rights of food manufacturers. Whether the rule would survive constitutional scrutiny or not is an open question because the compelled commercial speech doctrine is anything but clear. Courts are split over whether Zauderer’s rational basis test, Central Hudson’s intermediate scrutiny, or some combination of the two should apply to a mandated disclosure like FDA’s added sugars rule. This Paper explains that the added sugars rule is unique in the history of mandated nutrition labeling in that the rule is motivated largely by public health concerns and backed by reports that assert that consumers should limit their intake of added sugars. In contrast, correcting and preventing consumer deception has been a major driving force behind the remainder of FDA’s mandated nutrition labeling. Because of this distinct rationale, the added sugars rule does not fit neatly into any currently existing compelled commercial speech test. This Paper uses the added sugars rule to highlight the deficiencies in the existing tests. Finally, this Paper proposes a new compelled commercial speech test that would adequately balance the interest of all of the effected parties: the government, the public, and food manufacturers.

  9. 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 to cloza......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....

  10. Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

    Science.gov (United States)

    Khan, Archie A; Shekh-Ahmad, Tawfeeq; Khalil, Ayatakin; Walker, Matthew C; Ali, Afia B

    2018-03-25

    A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry. Electrophysiological intracellular whole-cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy (in vivo kainic acid-induced) and in vitro (Mg 2+ -free-induced) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg kg -1 ) at zero time and 90 minutes post status epilepticus (SE) induced with kainic acid. Bath-application of CBD (10 μM), dampened excitability at unitary synapses between pyramidal cells, but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK, and pyramidal cells in a cell type-specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction of atrophy and death of PV- and CCK-expressing interneurons after CBD treatment. In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function. This article is protected by copyright. All rights reserved.

  11. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    Science.gov (United States)

    Giordano, Carmela; Marchiò, Maddalena; Timofeeva, Elena; Biagini, Giuseppe

    2014-01-01

    mechanisms involved in the beneficial effects of KDs. In this review, we summarize the current evidence for altered regulation of the synthesis of neuropeptides and peripheral hormones in response to KDs, and we try to define a possible role for specific neuroactive peptides in mediating the antiepileptic properties of diet-induced ketogenesis. PMID:24808888

  12. 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.

  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. 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.

  15. EVALUATING SKILLS AND CHALLENGES AS ANTECEDENTS OF COMPELLING ONLINE INFORMATION-SEEKING EXPERIENCES

    Directory of Open Access Journals (Sweden)

    Alina LAZOC

    2013-06-01

    Full Text Available In contemporary information societies, consumers are increasingly expected to be proficient users of online information to support and guide their buying decisions. Due to the world wide web and its availability on a wide range of connectable devices, information from infinite commercial and non-commercial sources can be instantly accessed and used. However, consumers’ level of self-efficacy in dealing with technology and the wide range of information content as well as the extent to which they feel cognitively challenged by the technological and content issues may significantly influence the intensity of their involvement with companies’ marketing information. Based on the online flow theory, describing total involvement experiences, as well as on recent developments of the information literacy construct, in the present paper we propose a research instrument for assessing two essential preconditions of optimal, highly engaging consumer online information-seeking experiences. We posit that consumers have compelling online search experiences when the level of both their technical and their cognitive skills match the informational challenges perceived in the online medium. Nevertheless, the following study represents only the first step in a complex scale development process and in building and testing the structural model describing causal relationships between flow constructs.

  16. Jezero Crater, Mars, as a Compelling Site for Future In Situ Exploration

    Science.gov (United States)

    Goudge, T. A.; Ehlmann, B. L.; Fassett, C. I.; Head, J. W.; Mustard, J. F.; Mangold, N.; Gupta, S.; Milliken, R. E.; Brown, A. J.

    2017-01-01

    Jezero is a approximately 45 km diameter impact crater located in the Nili Fossae region of Mars. Jezero is an outstanding site to address key questions of ancient Mars climate, habitability, and volcanic history because: (a) It hosted an open-basin lake during the era of valley network formation [1,2], which ceased at approximately the Noachian-Hesperian boundary [3]. (b) It contains two delta deposits [1,4] with Fe/Mg-smectite and Mg-carbonate sediment [4-7] (the only exposure of lacus-trine shoreline carbonates seen so far on Mars). (c) The depositional environment and mineral assemblage of the delta are promising for the concentration and preservation of organic matter [5,8]. (d) The diverse geologic units in Jezero are in clear stratigraphic context [7]. The Jezero paleolake system has been thoroughly investigated at a variety of scales, including work on: the mineralogy of the delta deposits [4-6] and watershed [7], as well as the morphology and sedimentology of the basin [9] and delta deposits [1,4]. The geologic context of Jezero is also well-studied given the broad suite of alteration minerals exposed in the ancient stratigraphies of the Nili Fossae region [e.g., 6,10-13]. Here we present an overview of the units accessible for exploration in the Jezero basin, including questions and hypotheses that can be tested through analysis in situ and of returned samples. This is particularly timely given the upcoming Mars 2020 mission, for which Jezero is one of the final eight landing sites [14]. Primary science objectives for Mars 2020 are to: (1) characterize the geologic history of a site with "evidence of an astrobiologically-relevant ancient environment and geologic diversity"; (2) assess the habitability and "potential evidence of past life" in units with "high biosignature preservation potential"; and (3) cache scientifically compelling samples for potential return to Earth [15].

  17. Compelled Body-Weight Shift Approach in Rehabilitation of Individuals with Chronic Stroke

    Science.gov (United States)

    Aruin, Alexander S.; Rao, Noel; Sharma, Asha; Chaudhuri, Gouri

    2013-01-01

    Purpose To evaluate the effectiveness of the Compelled Body Weight Shift (CBWS) therapy approach in the rehabilitation of individuals with chronic stroke. CBWS involves a forced shift of body weight towards a person’s affected side by means of a shoe insert that establishes a lift of the non-affected lower extremity. Method Eighteen individuals with chronic, unilateral stroke (mean age 57.7 ± 11.9 years, with a range of 35–75 years, mean time since stroke 6.7±3.9 years with a range of 1.1–14.1 years) who showed asymmetrical stance were randomly divided into two groups: the experimental group received a six-week physical therapy combined with CBWS therapy and the control group received only physical therapy. Both groups underwent a battery of identical tests (Fugl-Meyer assessment, Berg Balance Scale, weight bearing, and gait velocity) before the start of the rehabilitation intervention, following its completion, and three months after the end of therapy. Results After the intervention, weight bearing on the affected side (measured with the Balance Master®) increased in the experimental group to a larger degree compared to the control group (9.7% vs. 6.4%). Similarly, gait velocity increased 10.5% in the experimental group compared to the control group. Improvements in weight bearing and gait velocity were maintained in the experimental group after the three month retention period. Conclusion The study outcome revealed that a six-week intervention involving CBWS therapy could result in a long-lasting improvement of the symmetry of weight bearing and velocity of gait in individuals with chronic stroke. PMID:23192720

  18. Compelled by the Diagram: Thinking through C. H. Waddington’s Epigenetic Landscape

    Directory of Open Access Journals (Sweden)

    Matthew Allen

    2015-08-01

    Full Text Available Normal 0 false false false EN-US JA X-NONE /* 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:Verdana;} Between 1940 and about 1960, Conrad Hal Waddington produced several illustrations to explain a concept central to his theories of developmental biology. The concept Waddington explained, the epigenetic landscape, was not based on settled science, and its implications were not easy to grasp. Unlike proponents of the most successful contemporary biological theory, Waddington was committed to including all biological phenomena–no matter how complex or unusual–in a single theoretical system. His intellectual style and use of images matched his ambition. Waddington used compelling images to get his readers to engage with and work through his theories. His images used a shifting, even contradictory, set of metaphors and analogical models, from train yards to crafted topological surfaces. Through an analysis of Waddington’s images and theories, I show that taking a close look at what scientific images show and how they show it is important for the historiography of science. Images can be effective at drawing viewers in, confounding them, and prodding them to ask questions; this is one reason images are necessary for science.

  19. Toward Effective and Compelling Instruction for High School eCommerce Students: Results from a Small Field Study

    Science.gov (United States)

    Luterbach, Kenneth J.; Rodriguez, Diane; Love, Lakecia

    2012-01-01

    This paper describes an instructional development effort to create effective and compelling instruction for eCommerce students. Results from a small field study inform the development project. Four high school students in an eCommerce course completed the standalone tutorial developed to teach them how to create a web page in the HyperText Markup…

  20. 18 CFR 385.410 - Objections to discovery, motions to quash or to compel, and protective orders (Rule 410).

    Science.gov (United States)

    2010-04-01

    ... clearly state the grounds on which the participant bases its objection. (4) Objections to compile or... compel discovery, if: (1) A participant to whom a data request is made or upon whom an interrogatory is served under Rule 406 fails or refuses to make a full, complete, and accurate response; (2) A person...

  1. Topiramate as concomitant antiepileptic treatment; an isolated perioperative hypofibrinogenaemia.

    Science.gov (United States)

    Iglesias Morales, C; Duca Rezzulini, F; Latre Saso, C; Gonzalez Paniagua, C; Iturri Clavero, F; Martinez Ruiz, A

    2016-04-01

    A description of a case is presented of an isolated hypofibrinogenaemia acquired in relation to taking topiramate used as concomitant treatment of a drug resistant epilepsy. The hypofibrinogenaemia developed in the course of a month after the introduction of the drug, and was diagnosed in the perioperative period. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. The role of antiepileptic drugs in free radicals generation and antioxidant levels in epileptic patients.

    Science.gov (United States)

    Eldin, Essam Eldin Mohamed Nour; Elshebiny, Hosam Abdel-Fattah; Mohamed, Tarek Mostafa; Abdel-Aziz, Mohamed Abdel-Azim; El-Readi, Mahmoud Zaki

    2016-01-01

    Many risk factors are encountered during the pathogenesis of epilepsy. In this study, the effect of seizure frequency on free radical generation and antioxidants levels in epileptic patients was evaluated. This study was carried out on 15 healthy controls (GI) and 60 epileptic patients treated with mono- or poly-therapy of carbamazepine, valproic acid, or phenytoin. The treated epileptic patients were divided into 2 main groups according to the seizure frequency: controlled seizure patients GII (n = 30) and uncontrolled seizure patients GIII (n = 30). GII included the GIIA subgroup (n = 15) which had been seizure free for more than 12 months and the GIIB subgroup (n = 15) which had been seizure free for a period from 6 to12 months. GIII included GIIIA (n = 15) and GIIIB (n = 15) for patients which had a seizure frequency of less than and more than four times/month, respectively. In comparison to the control group (GI), the levels of nitric oxide (NO) and malondialdehyde/creatinine ratio were significantly increased in GIIB, GIIIA, and GIIIB, while vitamins A and E levels were significantly decreased in GIIIB. Serum NO levels had significant negative correlations with serum vitamin E in the GIIA and GIIB groups, and with vitamin A in the GIIIA and GIIIB groups. However, serum NO had positive correlation with urinary MDA/Cr ratio. The imbalance between free radical generation and antioxidant system in epileptic patients may be a factor in seizure frequency.

  4. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    Directory of Open Access Journals (Sweden)

    Diego Lobos-Urbina

    2017-03-01

    Full Text Available Resumen Los pacientes con tumores cerebrales, primarios o metastásicos, presentan riego de desarrollar convulsiones durante la evolución de su enfermedad, por lo que se ha propuesto el uso profiláctico de anticonvulsivantes. Sin embargo, el efecto de esta intervención no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 12 revisiones sistemáticas que en conjunto incluyen ochenta estudios primarios. Doce corresponden a estudios aleatorizados, pero sólo dos responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que la prevención primaria con anticonvulsivantes podría no disminuir el riesgo de convulsiones en tumores o metástasis cerebrales, y se asocia a efectos adversos frecuentes.

  5. A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Singh Priyanka

    2009-01-01

    Full Text Available Abstract Background Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a Drosophila systems model of PTZ induced locomotor plasticity that is responsive to AEDs. Results We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of Drosophila adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase, two days (latent phase and seven days (behaviorally expressive phase showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set. Conclusion Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.

  6. Relationship of Child IQ to Parental IQ and Education in Children with Fetal Antiepileptic Drug Exposure

    OpenAIRE

    Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Clayton-Smith, Jill; Cohen, Morris J.; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

    2011-01-01

    Clinical trial designs need to control for genetic and environmental influences when examining cognitive outcomes in children for whom clinical considerations preclude randomization. However, the contributions of maternal and paternal IQ and education to pediatric cognitive outcomes are uncertain in disease populations. The NEAD Study is an ongoing prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy to determine if differential long-term ...

  7. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth

    DEFF Research Database (Denmark)

    Bech, Bodil Hammer; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard

    2014-01-01

    Dette studie undersøger, om brugen af antiepileptika under graviditeten kan øge risikoen for spontan abort eller dødfødsel. Resultaterne viser, at 16 ud af 100 gravide kvinder, som brugte antiepileptika, mistede fostret ved en spontan abort, mens det kun var 13 ud af 100 gravide kvinder, som ikke...... brugte antileptika. Der var dog forskel på, om de kvinder, der valgte at bruge antiepileptika under graviditeten, var diagnosticeret med epilepsi eller ej. I analyser alene af kvinder med epilepsi var der ingen forskel i risikoen for spontan abort, når kvinder, der indtog medicin i graviditeten, blev...... sammenlignet med kvinder, der ikke indtog medicin. Hos kvinder uden epilepsi havde de, der indtog medicin, en 30 % øget risiko for spontan abort sammenlignet med dem, der ikke indtog medicin. Forskellen kan måske forklares ved manglende kontrol for andre risikofaktorer (confounding). Analyserne tager højde...

  8. 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–P23 potentials amplitude, which reflects the decline in the activity of brain somatosensory system, represented by thalamo-cortical structures.Conclusion. Surface EMG and SSEP methods can be used for evaluation of treatment efficacy in cases of tic hyperkinesis and TS.

  9. Lacosamide and sodium channel-blocking antiepileptic drug cross-titration against levetiracetam background therapy.

    Science.gov (United States)

    Baulac, M; Byrnes, W; Williams, P; Borghs, S; Webster, E; De Backer, M; Dedeken, P

    2017-04-01

    To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB. In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period). The primary outcome was retention rate on LCM. Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued their SCB after cross-titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%). In patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB down-titration and stable background LEV-could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth

    DEFF Research Database (Denmark)

    Bech, Bodil Hammer; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard

    2014-01-01

    brugte antileptika. Der var dog forskel på, om de kvinder, der valgte at bruge antiepileptika under graviditeten, var diagnosticeret med epilepsi eller ej. I analyser alene af kvinder med epilepsi var der ingen forskel i risikoen for spontan abort, når kvinder, der indtog medicin i graviditeten, blev...... sammenlignet med kvinder, der ikke indtog medicin. Hos kvinder uden epilepsi havde de, der indtog medicin, en 30 % øget risiko for spontan abort sammenlignet med dem, der ikke indtog medicin. Forskellen kan måske forklares ved manglende kontrol for andre risikofaktorer (confounding). Analyserne tager højde...... for alder, samlivsforhold, indkomst, uddannelsesniveau, tidligere mental sygdom og tidligere stofmisbrug. Samlet indikerer undersøgelsen, at der generelt ikke er en øget risiko for at få en spontan abort ved brug af antiepileptika − i det mindste ikke for kvinder med epilepsi. Der blev ikke fundet nogen...

  11. Cognitive and behavioral outcomes among seizure-controlled children with partial epilepsy on antiepileptic drug monotherapy.

    Science.gov (United States)

    Burns, Thomas G; Ludwig, Natasha N; Tajiri, Tiffany N; DeFilippis, Nick

    2018-01-01

    The objective of this study was to assess cognitive performance and behavioral symptoms in a sample of children diagnosed with partial epilepsy who were seizure controlled on AED monotherapy for one year. Ninety-eight seizure-controlled children on AED monotherapy were included in this study. Specific AEDs examined included topiramate, divalproex sodium, lamotrigine, levetiracetam, and oxcarbazepine. Groups did not differ on age, region of focal epilepsy, or Full-Scale IQ. Direct measures included the WISC-IV and selected tests from the DKEFS (Verbal Fluency and Trail Making Test). Parent report measures included the BRIEF and the BASC-PRS. A series of ANOVAs revealed significant differences across the AED cohorts within many domains of cognitive functioning and behavioral presentation. Children prescribed divalproex sodium or topiramate demonstrated weaker working memory and verbal fluency, when compared with children prescribed other AEDs. Additionally, parents of children prescribed topiramate reported greater executive functioning and adaptive skills deficits. The pattern of findings suggests that children prescribed divalproex sodium or topiramate generally demonstrated a higher risk of cognitive and behavioral impairments compared to the other AEDs. Future prospective studies are required in order to better understand the relationship between AED type and these outcomes to inform clinical practice.

  12. 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

    AEDs (lamotrigine, topiramate, levetiracetam, gabapentin, oxcarbazepine, eslicarbazepine, felbamate, lacosamide, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin, and zonisamide) and specific congenital anomalies. METHODS: We searched PubMed and EMBASE to find observational...

  13. Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients.

    Science.gov (United States)

    Intravooth, Tassanai; Staack, Anke M; Juerges, Katharina; Stockinger, Jakob; Steinhoff, Bernhard J

    2018-03-30

    Recent evidence suggests that eslicarbazepine acetate (ESL) might be an appropriate alternative to carbamazepine (CBZ) and oxcarbazepine (OXC) due to its better safety profile. Hyponatremia may be one of the limiting safety problems in CBZ and OXC whereas it has been indicated that ESL is less sensitive for the adverse event. Since our clinical experience is different we investigated the incidence of hyponatremia in 560 consecutive adult inpatients treated at our center in 2015 by reviewing their medical records. Only CBZ, OXC and ESL were associated with hyponatremia. The incidence of hyponatremia induced by ESL was not statistically different from that induced by OXC (43% of patients with OXC and 33% with ESL, p > 0.05). Both were associated with hyponatremia more often than CBZ (16%). OXC-induced hyponatremia was dose-related, ESL-induced hyponatremia was not. Furthermore, both OXC- and ESL-induced hyponatremia occurred particularly often in elderly epilepsy patients. Thus, for elderly patients, both OXC and ESL should be considered with caution. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Identification of the antiepileptic racetam binding site in the synaptic vesicle protein 2A by molecular dynamics and docking simulations

    Science.gov (United States)

    Correa-Basurto, José; Cuevas-Hernández, Roberto I.; Phillips-Farfán, Bryan V.; Martínez-Archundia, Marlet; Romo-Mancillas, Antonio; Ramírez-Salinas, Gema L.; Pérez-González, Óscar A.; Trujillo-Ferrara, José; Mendoza-Torreblanca, Julieta G.

    2015-01-01

    Synaptic vesicle protein 2A (SV2A) is an integral membrane protein necessary for the proper function of the central nervous system and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam and its racetam analogs. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D) model was built. The model was refined by performing a molecular dynamics simulation (MDS) and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns) with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression. PMID:25914622

  15. Identification of the antiepileptic racetam binding site in the vesicle synaptic protein 2A by molecular dynamics and docking simulations

    Directory of Open Access Journals (Sweden)

    José eCorrea-Basurto

    2015-04-01

    Full Text Available Synaptic vesicle protein 2A (SV2A is an integral membrane protein necessary for the proper function of the central nervous system (CNS and is associated to the physiopathology of epilepsy. SV2A is the molecular target of the anti-epileptic drug levetiracetam (LEV and its racetam analogues. The racetam binding site in SV2A and the non-covalent interactions between racetams and SV2A are currently unknown; therefore, an in silico study was performed to explore these issues. Since SV2A has not been structurally characterized with X-ray crystallography or nuclear magnetic resonance, a three-dimensional (3D model was built. The model was refined by performing a molecular dynamics simulation (MDS and the interactions of SV2A with the racetams were determined by docking studies. A reliable 3D model of SV2A was obtained; it reached structural equilibrium during the last 15 ns of the MDS (50 ns with remaining structural motions in the N-terminus and long cytoplasmic loop. The docking studies revealed that hydrophobic interactions and hydrogen bonds participate importantly in ligand recognition within the binding site. Residues T456, S665, W666, D670 and L689 were important for racetam binding within the trans-membrane hydrophilic core of SV2A. Identifying the racetam binding site within SV2A should facilitate the synthesis of suitable radio-ligands to study treatment response and possibly epilepsy progression.

  16. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs

    NARCIS (Netherlands)

    de Vries, Max; Seppala, Lotta J.; Daams, Joost G.; van de Glind, Esther M. M.; Masud, Tahir; van der Velde, Nathalie

    2018-01-01

    Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is

  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. Can we predict drug response by volumes of the corpus callosum in newly diagnosed focal epilepsy?

    Science.gov (United States)

    Kim, Hyung Chan; Kim, Sung Eun; Lee, Byung In; Park, Kang Min

    2017-08-01

    The aim of this study was to investigate whether volumes of the corpus callosum could predict a response to antiepileptic drugs in patients with newly diagnosed focal epilepsy. Fifty-three patients with newly diagnosed focal epilepsy of unknown etiology and healthy subjects were enrolled in this study. First, we analyzed the differences in the volumes of the corpus callosum between patients with epilepsy and healthy subjects. Second, we divided patients with epilepsy into antiepileptic drug responders and drug nonresponders groups, according to their seizure controls, and evaluated the differences in the volumes of the corpus callosum between the groups. Third, we conducted correlation analyses between the volumes of the corpus callosum and mean diffusion measures in healthy subjects. The volumes of the corpus callosum in patients with epilepsy were significantly lower than those in normal controls ( p  =   .0001). Among epilepsy patients, the volumes of the corpus callosum were significantly lower in antiepileptic drug responders compared with nonresponders ( p  =   .0481), which was the only independent variable for predicting antiepileptic drug response (OR = 10.07, p  =   .0434). In addition, we found that the volumes of the corpus callosum were significantly correlated with the mean diffusion measures (fractional anisotropy, r  = .408, p  =   .0027; mean diffusivity, r  = -0.403, p  =   .0028) in normal controls. We demonstrated that the volumes of the corpus callosum were different according to antiepileptic drug responses in patients with newly diagnosed focal epilepsy, which might suggest that the volumes of the corpus callosum could be a new biomarker for predicting responses to antiepileptic drugs.

  19. 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.

  20. Antiepileptic and central nervous system depressant activity of Sechium edule fruit extract

    Directory of Open Access Journals (Sweden)

    Sayeed Mohammed Firdous Mumtaz

    2012-08-01

    Full Text Available The effect of ethanol extract of fruits of Sechium edule on antiepileptic and central nervous system (CNS depressant model was studied in rats. The extract (200 mg/kg body weight, orally significantly reduced the duration of various phases of convulsions in both MES-induce seizures and in PTZ-induced convulsion. In CNS depressant model, the locomotor activity was also decreased in a dose dependent manner as compared to control group the extract and the rota rod test revealed a significant loss of muscular coordination.

  1. 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.

  2. Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can Disrupt Brain Development

    Directory of Open Access Journals (Sweden)

    John W. Olney

    2013-07-01

    Full Text Available Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD, which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances. There is compelling evidence that exposure to alcohol during early embryogenesis (4th week of gestation can cause excessive death of cell populations that are essential for normal development of the face and brain. While this can explain craniofacial malformations and certain structural brain anomalies that sometimes accompany FASD, in many cases these features are absent, and the FASD syndrome manifests primarily as neurobehavioral disorders. It is not clear from the literature how alcohol causes these latter manifestations. In this review we will describe a growing body of evidence documenting that alcohol triggers widespread apoptotic death of neurons and oligodendroglia (OLs in the developing brain when administered to animals, including non-human primates, during a period equivalent to the human third trimester of gestation. This cell death reaction is associated with brain changes, including overall or regional reductions in brain mass, and long-term neurobehavioral disturbances. We will also review evidence that many drugs used in pediatric and obstetric medicine, including general anesthetics (GAs and anti-epileptics (AEDs, mimic alcohol in triggering widespread apoptotic death of neurons and OLs in the third trimester-equivalent animal brain, and that human children exposed to GAs during early infancy, or to AEDs during the third trimester of gestation, have a significantly increased incidence of FASD-like neurobehavioral disturbances. These findings provide evidence that exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. We propose that the mechanism by which

  3. 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.

  4. 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

  5. How sudden is a compelling desire to void? An observational cystometric study on the suddenness of this sensation.

    Science.gov (United States)

    De Wachter, Stefan; Wyndaele, Jean-Jacques

    2008-04-01

    To evaluate whether a compelling desire to void (CDV) is always perceived suddenly, or whether it can result from the gradual build-up of bladder-filling sensations. The pattern of filling sensations was evaluated during standard cystometric bladder filling in 75 patients who complained of urgency and showed detrusor overactivity during cystometry. Cystometric filling ended when a CDV was reported. The 'warning volume' is defined as the difference in volume between the first perception of filling and the volume at CDV. Different patterns of bladder-filling sensations were reported. A CDV occurred suddenly, without a preceding sensation in 13% of the patients, whereas 66% reported at least two normal preceding filling sensations before a CDV. The bladder volume at the CDV was significantly smaller in patients that reported no or just one preceding sensation compared with those that reported the normal pattern of two or three sensations (P perception was reported was not different regardless of whether it was described as a first sensation of filling, a first desire or a CDV (P = 0.42). The warning volumes were not different between patients with one or no standardized filling sensations (P = 0.7), but they were significantly smaller than in patients with two or three filling sensations (P = 0.85). A CDV can occur suddenly if normal filling sensation is disturbed, but also gradually if normal filling sensation is preserved. In cases of disturbed filling sensation, the volume at CDV and the warning volume are significantly lower.

  6. Enhancing shareholder value: Making a more compelling energy efficiency case to industry by quantifying non-energy benefits

    International Nuclear Information System (INIS)

    Pye, M.; McKane, A.

    1999-01-01

    This paper describes a more compelling case for industry to promote the non-energy benefits of energy efficiency investments. They do this in two ways to actively appeal to chief executive officers' (CEOs') and chief financial officers' (CFOs') primary responsibility: to enhance shareholder value. First, they describe the use of a project-by-project corporate financial analysis approach to quantify a broader range of productivity benefits that stem from investments in energy-efficient technologies, including waste reduction and pollution prevention. Second, and perhaps just as important, they present such information in corporate financial terms. These standard, widely accepted analysis procedures are more credible to industry than the economic modeling done in the past because they are structured in the same way corporate financial analysts perform discounted cashflow investment analyses on individual projects. Case studies including such financial analyses, which quantify both energy and non-energy benefits from investments in energy-efficient technologies, are presented. Experience shows that energy efficiency projects' non-energy benefits often exceed the value of energy savings, so energy savings should be viewed more correctly as part of the total benefits, rather than the focus of the results. Quantifying the total benefits of energy efficiency projects helps companies understand the financial opportunities of investments in energy-efficient technologies. Making a case for investing in energy-efficient technologies based on energy savings alone has not always proven successful. Evidence suggests, however, that industrial decision makers will understand energy efficiency investments as part of a broader set of parameters that affect company productivity and profitability

  7. Diagnostic investigation of porcine periweaning failure-to-thrive syndrome: lack of compelling evidence linking to common porcine pathogens.

    Science.gov (United States)

    Huang, Yanyun; Gauvreau, Henry; Harding, John

    2012-01-01

    Porcine periweaning failure-to-thrive syndrome (PFTS), an increasingly recognized syndrome in the swine industry of North America, is characterized by the anorexia of nursery pigs noticeable within 1 week of weaning, and progressive loss of body condition and lethargy during the next 1-2 weeks. Morbidity caused by PFTS is moderate, but case fatality is high. The etiology of PFTS is presently unknown and may include infectious agent(s), noninfectious factors, or both. PFTS was identified in a high health status farm with good management in early 2007. A diagnostic investigation was undertaken to identify the pathological lesions of, and infectious agents associated with, pigs demonstrating typical clinical signs. Affected (PFTS-SICK) and unaffected (PFTS-HLTHY) pigs from an affected farm, and unaffected pigs from 2 unaffected farms, were examined. The most prevalent lesions in PFTS-SICK pigs were superficial lymphocytic fundic gastritis, atrophic enteritis, superficial colitis, lymphocytic and neutrophilic rhinitis, mild nonsuppurative meningoencephalitis, and thymic atrophy. Rotavirus A and Betacoronavirus 1 (Porcine hemagglutinating encephalomyelitis virus) were identified only in PFTS-SICK pigs, but the significance of the viruses is uncertain because PFTS is not consistent with the typical presentation following infection by these pathogens. Porcine reproductive and respiratory syndrome virus, Porcine circovirus-2, Influenza A virus, Alphacoronavirus 1 (Transmissible gastroenteritis virus), Torque teno virus 1, Brachyspira hyodysenteriae, and Brachyspira pilosicoli were not identified in PFTS-SICK pigs. Suid herpesvirus 2 (Porcine cytomegalovirus), Porcine enteric calicivirus, Torque teno virus 2, pathogenic Escherichia coli, and coccidia were detected in both PFTS-SICK and PFTS-HLTHY pigs. It was concluded that there is a lack of compelling evidence that PFTS is caused by any of these pathogens.

  8. 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.

  9. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    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.

  10. Drug Treatment of Seizures and Epilepsy in Newborns and Children.

    Science.gov (United States)

    Dang, Louis T; Silverstein, Faye S

    2017-12-01

    The mainstay of treatment of childhood epilepsy is to administer antiepileptic drugs (AEDs). This article provides an overview of the clinical approach to drug treatment of childhood epilepsy, focusing on general principles of therapy and properties of recently introduced medications. Initiation and cessation of therapy, adverse medication effects, drug interactions, indications for the various AEDs, and off-label use of AEDs are reviewed. The distinct challenges in treatment of epileptic spasms and neonatal seizures are addressed. Finally, ideas for the future of drug treatment of childhood epilepsy are presented, with particular attention to precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 39 CFR 230.17 - If an attempt is made to compel production of reports and records during the employee's testimony...

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false If an attempt is made to compel production of reports and records during the employee's testimony, what is an Office of Inspector General employee... Information Act and shall be handled pursuant to 39 CFR 230.5. ...

  12. 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.

  13. Antiepileptic effects of electroacupuncture vs vagus nerve stimulation on cortical epileptiform activities.

    Science.gov (United States)

    Zhang, Jian-Liang; Zhang, Shi-Ping; Zhang, Hong-Qi

    2008-07-15

    Introduced about two decades ago, vagus nerve stimulation (VNS) therapy has been increasingly used for the treatment of refractory epilepsy recently. This study was set out to compare the effects between VNS and electroacupuncture (EA) on pentylenetetrazole (PTZ) induced epileptiform activities in the rat cerebral cortex. Under general anesthesia, the parietal cortex of the rat (n=20) was exposed to record the cortical epileptiform activities. The left vagus nerve was stimulated at 30 Hz, 1 mA or 3 mA for 5 min. For EA, "Dazhui" acupoint (GV14) was stimulated with a pair of acupuncture needles with the same parameters. The results show that both VNS and EA at either 1 mA or 3 mA could inhibit the PTZ-induced cortical epileptiform activities, and higher stimulation (3 mA) was not associated with a greater inhibition. In the cases that showed inhibitory responses, there were no statistically significant differences between the two modalities, implying that EA could be comparable to VNS in the treatment of epilepsy. Thus, under current experimental settings, the antiepileptic effect induced by electrical stimulation appeared not vagal specific, and EA could be a good alternative to VNS in the management of epilepsy.

  14. Pharmacogenetic studies of epilepsy drugs: are we there yet?

    Science.gov (United States)

    Spurr, Nigel K

    2006-05-01

    One of the mantras of scientists working in the field of pharmacogenetics is 'the right dose for the right patient'. A recent article has gone someway towards demonstrating that this goal can be achieved using genetic approaches. It is one of the first reports to show that a specific polymorphism can predict the maximum tolerated dose of two anti-epileptic drugs. However, further studies are necessary to validate these observations.

  15. 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.

  16. Cutaneous adverse drug reactions in Indian population: A systematic review

    Science.gov (United States)

    Patel, Tejas K; Thakkar, Sejal H; Sharma, DC

    2014-01-01

    Background: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. Aims: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. Materials and Methods: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing “definite” and “probable” categories of causality analysis were labeled as “definite and probable causality (DPC) studies”. The other included studies were labeled as “non-DPC studies”. Results: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), β-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS

  17. 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

    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...

  18. The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models

    DEFF Research Database (Denmark)

    Plum, Jakob Munk; Nøhr, Martha Kampp; Hansen, Steen H

    2014-01-01

    , such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of amino...... acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34±3 and 53±2%, respectively, at a concentration of 30mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27mM (log......Km is 1.43±0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting...

  19. The absorptive flux of the anti-epileptic drug substance vigabatrin is carrier-mediated across Caco-2 cell monolayers

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Hansen, Steen Honoré; Brodin, Birger

    2014-01-01

    of vigabatrin in Caco-2 cells, a cell culture model of the small intestinal epithelium. The uptake and transepithelial flux of vigabatrin was measured using an LC-MS method for quantification. Transepithelial transport of vigabatrin was shown to be proton-dependent and polarized in the apical-to-basolateral (A...... of the human proton-coupled amino acid transporter (hPAT1) to the apical solution. The present study indicates that the transepithelial A-B flux of vigabatrin is mainly mediated by hPAT1 in Caco-2 cells at dose-relevant concentrations....

  20. Uptake of three antibiotics and an anti-epileptic drug by wheat plants spray irrigated with wastewater treatment plant effluent

    Science.gov (United States)

    With rising demands on water supplies necessitating water reuse, wastewater treatment plant (WWTP) effluent is often used to irrigate agricultural lands. Emerging contaminants, like pharmaceuticals and personal care products (PPCPs), are frequently found in effluent due to limited removal during WWT...

  1. Investigation of PON1 activity and MDA levels in patients with epilepsy not receiving antiepileptic treatment

    Directory of Open Access Journals (Sweden)

    Dönmezdil N

    2016-04-01

    Full Text Available Nilüfer Dönmezdil, Mehmet Uğur Çevik, Hasan Hüseyin Özdemir, Muhterem Taşin Department of Neurology, Dicle University, Diyarbakır, Turkey Purpose: There are many studies dedicated to researching the etiopathogenesis of epilepsy. In such research, oxidative and antioxidant indicators of etiopathogenesis have also been examined under the scope. Drawing on a group of patients with epilepsy who were receiving no treatment, we have tried to evaluate whether or not an increase in oxidative indicators is linked directly with the disorder, independent of epileptic medicaments.Methods: Thirty people in good health and 30 newly diagnosed with epilepsy and who received ambulatory treatment in the polyclinic of the Neurology Department took part in the study. The tests relating to serum malondialdehyde (MDA levels and paraoxonase 1 (PON1 activity were carried out in the biochemistry laboratory.Results: Even though the levels of MDA in the patient group (14.34±3.59 nmol/mL were found to be high compared to those of the control group, which consisted of people in good health (13.53±3.56 nmol/mL, there was no statistically significant difference. PON1 activity in the serum taken from people in the patient group (0.65±0.17 was lower in comparison to that observed in the serum of the control group (0.71±0.17 U/L. Nonetheless, it was not so low as to have significance from a statistical point of view.Conclusion: We conclude that such a high level of oxidative parameters should have been related to the disease and that statistically significant findings that emerged in some other studies could have been related to an antiepileptic treatment. Keywords: epilepsy, paraoxonase 1, malondialdehyde, oxidative stress, epilepsy, biochemical marker

  2. Comparative analysis of cost and efficacy for mono and dual therapy of antiepileptics among children

    Directory of Open Access Journals (Sweden)

    Easwaran Vigneshwaran

    2017-01-01

    Full Text Available Introduction: Developing countries contribute to major number of patients living with epilepsy, around five million people are living with epilepsy in India alone. Most of the epileptic children may require multiple antiepileptic therapy due to the failure of monotherapy. Basic research evidence suggest that sodium valproate and carbamazepine (CBZ may have synergistic anticonvulsant effects when they are used together. In addition to that, chronic disorders make the patients economically weak and produce more burden. Aim and Objective: Therefore, this study was designed to compare the efficacy of valproate monotherapy with valproate and CBZ dual therapy. Methodology: It is a prospective, comparative study conducted at a secondary care referral hospital and private clinic. A nonprobabilistic convenient sampling was done to recruit the study subjects. A total of fifty subjects were recruited into the present study, and they were divided into two groups, i.e., monotherapy group (CBZ and dual therapy group (CBZ and valproate. After providing appropriate counseling, subjects were interviewed to estimate the quality of life (QOL using child version of TNO-AZL Children's Quality of Life questionnaire. Hospital patient records, prescription data from the pharmacy were also used to obtain the direct and indirect cost of treatment. Results: Our study results showed that monotherapy has a potential to produce a higher level of QOL than dual therapy. It also involved with decreased seizure frequency. Although there was no statistically significant difference in terms of cost for both the treatment groups, still dual therapy is associated with higher cost burden. The average costs per QOL and changes in the frequency of seizure are also identified to produce higher economic burden to the patients.Conclusion: Thus, the present study has concluded that monotherapy may be considered as better cost-effective treatment in partial seizures than dual therapy

  3. Is there any benefit from short-term perioperative antiepileptic prophylaxis in patients with chronic subdural haematoma? A retrospective controlled study.

    Science.gov (United States)

    Battaglia, Fabrice; Plas, Benjamin; Melot, Anthony; Noudel, Rémy; Sol, Jean-Christophe; Roche, Pierre-Hugues; Lubrano, Vincent

    2015-10-01

    Chronic subdural haematoma is a common pathology, which can be complicated by seizures. Seizures may worsen the outcome of patients presenting with a chronic subdural haematoma. However, since the overall and postoperative incidence of seizures and their impact on patients' outcome has been diversely appreciated in the literature, the interest of routine antiepileptic prophylaxis remains a controversial question. We retrospectively investigated 99 patients who were surgically treated for a chronic subdural haematoma in two French academic hospitals: 48 patients received antiepileptic prophylaxis (group A) and were compared with a group of 51 patients who did not receive any antiepileptic prophylaxis (group B). Incidence of perioperative seizures was determined, and potential risk factors for epilepsy were analysed. Overall postoperative seizure incidence was 5.1%. There was a slight trend towards a lower incidence of seizures in patients who had received antiepileptic prophylaxis, but no significant difference was found between the two groups (4.2% in group A versus 5.9% in group B, P=0.697). Seizures were not correlated with increased death. No risk factor for seizures was identified. Our retrospective data showed there is no benefit of perioperative antiepileptic prophylaxis in patients surgically treated for chronic subdural haematoma. Since other authors have shown conflicting results, sufficiently powered prospective randomized study should be conducted in order to confirm these results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Computer-Aided Recognition of ABC Transporters Substrates and Its Application to the Development of New Drugs for Refractory Epilepsy.

    Science.gov (United States)

    Couyoupetrou, Manuel; Gantner, Melisa E; Di Ianni, Mauricio E; Palestro, Pablo H; Enrique, Andrea V; Gavernet, Luciana; Ruiz, Maria E; Pesce, Guido; Bruno-Blanch, Luis E; Talevi, Alan

    2017-01-01

    Despite the introduction of more than 15 third generation antiepileptic drugs to the market from 1990 to the moment, about one third of the epileptic patients still suffer from refractory to intractable epilepsy. Several hypotheses seek to explain the failure of drug treatments to control epilepsy symptoms in such patients. The most studied one proposes that drug resistance might be related with regional overactivity of efflux transporters from the ATP-Binding Cassette (ABC) superfamily at the blood-brain barrier and/or the epileptic foci in the brain. Different strategies have been conceived to address the transporter hypothesis, among them inhibiting or down-regulating the efflux transporters or bypassing them through a diversity of artifices. Here, we review scientific evidence supporting the transporter hypothesis along with its limitations, as well as computer-assisted early recognition of ABC transporter substrates as an interesting strategy to develop novel antiepileptic drugs capable of treating refractory epilepsy linked to ABC transporters overactivity.

  5. The impact of non-urologic drugs on sexual function in men

    Directory of Open Access Journals (Sweden)

    Ferdinando Fusco

    2014-03-01

    Full Text Available Sexual dysfunctions have commonly been reported as the resulting side effects of many drugs. To understand the impact of a single drug, the mechanism of action of the most commonly prescribed drugs and the physiological mechanisms of sexual function have to be taken into dual consideration. Psychotropic drugs (Antidepressants, Antipsychotics and Antiepileptic in particular result in both short and long-term effects on sexual function. Antihypertensive drugs have also produced evidence certifying their role in determining sexual dysfunction. Patients affected with sexual dysfunction are often aged and assume several drugs and, while Iatrogenic sexual dysfunction is prevalent in men, urological drugs are not the only drugs to be held accountable. Many different drugs acting on different sites and with several mechanisms of action can induce sexual dysfunction. The drug classes involved are widely diffused and frequently assumed in combination therapies.

  6. Drug Facts

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    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  7. ANTIEPILEPTIC MEDICATION IN PREGNANCY - LATE EFFECTS ON THE CHILDRENS CENTRAL-NERVOUS-SYSTEM DEVELOPMENT

    NARCIS (Netherlands)

    VANDERPOL, MC; HADDERSALGRA, M; HUISJES, HJ; TOUWEN, BCL

    In a follow-up study long-term effects of antenatal exposure to two anticonvulsant drugs, phenobarbital and carbamazepine on central nervous system development were evaluated. Children aged 6 to 13 years of epileptic mothers who used phenobarbital (n = 13), carbamazepine (n = 12), phenobarbital plus

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Drug Facts

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  12. Cell motility is inhibited by the antiepileptic compound, valproic acid and its teratogenic analogues

    DEFF Research Database (Denmark)

    Walmod, P S; Foley, A; Berezin, A

    1998-01-01

    Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. In this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer assisted image analy......-actin and of a series of focal adhesion proteins, indicating that the effect of VPA on cell motility may be causally related to increased cell-substratum interactions or to alterations in the organisation or dynamics of the actin cytoskeleton.......Valproic acid (VPA) is an established human teratogen that causes neural tube defects in 1-2% of human foetuses exposed to the drug during early pregnancy. In this study, individual cell motility was evaluated using short- and long-term time-lapse video-recording and computer assisted image...... analysis, and it was found that VPA and selected VPA-analogues inhibited individual cell motility of L-cells in a dose-dependent manner. The compounds caused a decrease in the root-mean-square speed, S, and in the rate of diffusion, R, but an increase in the time of persistence in direction, P. Using short...

  13. Drug poisoning and associated factors in western Saudi Arabia: A five-year retrospective chart review (2011-2016).

    Science.gov (United States)

    Alzahrani, Sami H; Alqahtani, Ali H; Farahat, Fayssal Mostafa; Elnour, Mohammed Abdel Galil; Bashawri, Jamil

    2017-01-01

    Drug poisoning is a globally common cause of emergency-room admissions. This study explores drug-poisoning prevalence patterns, associated risk factors (gender, age and exposure circumstances), and outcomes in western Saudi Arabia. Retrospective analysis of Clinical drug poisoning cases (2011-2016). The data were retrieved from the Saudi Ministry of Health's record and Patients' medical charts were analyzed. The Ministry of Health received 1,474 reports of drug poisoning during 2011-2016. More than half involved females (n=885, 60%) or young children (0-4 years old) (n=764, 51.8%) and occurred accidentally (n=786, 53.3%); almost all had an oral route of poisoning (n=1,466, 99.5%). The cases most frequently involved analgesic and non-steroidal anti-inflammatory drugs (n=373, 25.2%); antiepileptic, antipsychotic, psychoactive, and anxiolytic drugs (n=229, 16.3%); antihistamine, asthma, flu, and cough drugs (n=157, 12.0%); and antibiotic, anti-fungal; and antiprotozoal drugs (n=74, 5.0%). Antidotes were administered in only 2.2% of cases, and no deaths were reported. The drug poisoning cases involved females and young children (younger than 5 years old) and the most cases were accidental, and the most commonly used drugs were analgesics (Panadol), followed by antipsychotics, antihistamines, and antiepileptics (Tegretol).

  14. Drug Addiction

    Science.gov (United States)

    ... attempt to stop taking the drug Recognizing unhealthy drug use in family members Sometimes it's difficult to ... sold to support drug use Recognizing signs of drug use or intoxication Signs and symptoms of drug ...

  15. Drug Allergy

    Science.gov (United States)

    ... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...

  16. Adverse drug reactions and organ damage: The skin.

    Science.gov (United States)

    Marzano, Angelo V; Borghi, Alessandro; Cugno, Massimo

    2016-03-01

    Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens-Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  17. Drug Facts

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    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  18. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  19. Investigational new drugs for focal epilepsy.

    Science.gov (United States)

    Mula, Marco

    2016-01-01

    For more than 30 years, antiepileptic drug development has been based on specific assumptions regarding the neurobiology of epilepsy but all marketed drugs have not changed the proportion of drug refractory patients. It is, therefore, evident that new molecular targets need to be identified. Advances in neurobiology and molecular pharmacology are bringing into the epilepsy field new neurochemical functions such as those modulated by cannabinoid, serotonin, melatonin and galanin receptors. Among all the different compounds, the melatonin type 3 receptor agonist beprodone and cannabidiol are those at the more advanced stage of development. Interestingly, despite the structural analogies with tetrahydrocannabinol, the anticonvulsant activity of cannabidiol is not mediated by an interaction with cannabinoid receptors. Neurosteroids represent another remarkable class of drugs, and among them, ganaxolone is at the most advanced stage of development. Furthermore, for the first time, potential disease-modifying agents and techniques are entering the epilepsy market. Rapalogues such as everolimus and the antibiotic minocycline are currently under development for specific epileptic syndromes like tuberous sclerosis or Angelman syndrome. Finally, optogenetics, though still at an early stage of development, represents a futuristic therapeutic strategy for drug-refractory epilepsy.

  20. Drug Facts

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    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  1. Drug Facts

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    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  2. Drug Facts

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    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  3. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  4. Drug Facts

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    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  5. Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice

    Science.gov (United States)

    Viswanatha, Gollapalle L.; Venkataranganna, Marikunte V.; Prasad, Nunna Bheema Lingeswara; Ashok, Godavarthi

    2016-01-01

    Objectives: This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. Materials and Methods: Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. Results: In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels (P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. Conclusion: These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain. PMID:27757273

  6. Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice.

    Science.gov (United States)

    Viswanatha, Gollapalle L; Venkataranganna, Marikunte V; Prasad, Nunna Bheema Lingeswara; Ashok, Godavarthi

    2016-01-01

    This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES ( P < 0.01) and PTZ-induced ( P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels ( P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain.

  7. KILOPARSEC-SCALE SPATIAL OFFSETS IN DOUBLE-PEAKED NARROW-LINE ACTIVE GALACTIC NUCLEI. I. MARKERS FOR SELECTION OF COMPELLING DUAL ACTIVE GALACTIC NUCLEUS CANDIDATES

    Energy Technology Data Exchange (ETDEWEB)

    Comerford, Julia M. [Astronomy Department, University of Texas at Austin, Austin, TX 78712 (United States); Gerke, Brian F. [Kavli Institute for Particle Astrophysics and Cosmology, M/S 29, Stanford Linear Accelerator Center, 2575 Sand Hill Road, Menlo Park, CA 94725 (United States); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, MS 169-221, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Cooper, Michael C. [Center for Galaxy Evolution, Department of Physics and Astronomy, University of California, Irvine, 4129 Frederick Reines Hall, Irvine, CA 92697 (United States); Weiner, Benjamin J. [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Newman, Jeffrey A. [Department of Physics and Astronomy, Pittsburgh Particle Physics, Astrophysics, and Cosmology Center, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Madsen, Kristin [Space Radiation Laboratory, California Institute of Technology, MS 105-24, Pasadena, CA 91125 (United States); Barrows, R. Scott [Arkansas Center for Space and Planetary Sciences, University of Arkansas, Fayetteville, AR 72701 (United States)

    2012-07-01

    criteria for selecting the most promising dual AGN candidates from the full sample of double-peaked narrow-line AGNs. Using these criteria, we determine the 17 most compelling dual AGN candidates in our sample.

  8. Utilization of the Arkansas Prescription Monitoring Program to combat prescription drug abuse

    Directory of Open Access Journals (Sweden)

    Rebecca Rittenhouse

    2015-01-01

    Conclusion: Compelling more users of the AR PMP to be prompted to access the program by the involvement of a CS prescription or by requirements per office/facility policy may increase frequency of use of the program and thereby changes in health care practices to combat prescription drug abuse.

  9. 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.

  10. Drug Facts

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    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What ... Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the principal biomedical and behavioral research agency ...

  11. Drug Facts

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    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  12. Hazardous Drugs

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    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  13. Drug Facts

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    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment ...

  14. Drug Reactions

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    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  15. Drug Facts

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    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  16. Club Drugs

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    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... regarding prevention and treatment of MDMA. ( September 2017 ) View all related publications Related NIDA Notes Articles Narrative ...

  17. Drug Facts

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    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  18. Drug Facts

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    Full Text Available ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ...

  19. Drug Facts

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    Full Text Available ... Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her ...

  20. From drug delivery systems to drug release, dissolution, IVIVC, BCS, BDDCS, bioequivalence and biowaivers.

    Science.gov (United States)

    Karalis, Vangelis; Magklara, Eleni; Shah, Vinod P; Macheras, Panos

    2010-09-01

    This is a summary report of the conference on drug absorption and bioequivalence issues held in Titania Hotel in Athens (Greece) from the 28(th) to the 30(th) of May 2009. The conference included presentations which were mainly divided into three sections. The first section focused on modern drug delivery systems such as polymer nanotechnology, cell immobilization techniques to deliver drugs into the brain, nanosized liposomes used in drug eluting stents, encapsulation of drug implants in biocompatible polymers, and application of differential scanning calorimetry as a tool to study liposomal stability. The importance of drug release and dissolution were also discussed by placing special emphasis on camptothecins and oral prolonged release formulations. The complexity of the luminal environment and the value of dissolution in lyophilized products were also highlighted. The second session of the conference included presentations on the Biopharmaceutics Classification Scheme (BCS), the Biopharmaceutics Drug Disposition Classification System (BDDCS), and the role of transporters in the classification of drugs. The current status of biowaivers and a modern view on non-linear in vitro-in vivo (IVIVC) correlations were also addressed. Finally, this section ended with a special topic on biorelevant dissolution media and methods. The third day of the conference was dedicated to bioequivalence. Emphasis was placed on high within-subject variability and its impact on study design. Two unresolved issues of bioequivalence were also discussed: the use of generic antiepileptic drugs and the role of metabolites in bioequivalence assessment. Finally, the conference closed with a presentation of the current regulatory status of WHO and EMEA.

  1. Metabolism of Drugs Used in the Therapy of Seizures: An Analytical Point of View. Part 1.

    Science.gov (United States)

    Mandrioli, Roberto; Mercolini, Laura

    2017-10-16

    Seizures are aetiologically and clinically heterogeneous neurological disorders that are currently treated using a wide array of drugs, belonging to equally heterogeneous chemical classes. Some of them are known as "antiepileptic drugs" (AEDs), due to their main field of use, while others (such as benzodiazepines) are frequently used for other conditions as well as for seizures. Due to their different chemical properties and mechanisms of activity, the metabolic characteristics of anti-seizure drugs can vary widely, also producing big differences in terms of safety, efficacy and therapeutic suitability. Scopus and PubMed databases were searched for the most significant papers centered on metabolism and analysis of the following antiepileptics: carbamazepine, oxcarbazepine, lamotrigine, phenytoin, ethosuximide, gabapentin, vigabatrin, topiramate, levetiracetam and valproic acid. The most important studies on the metabolic characteristics of several AEDs are reported and briefly discussed in this review; moreover, the analytical methods used to determine biological levels of these drugs during therapy are also described and commented upon, and their main characteristics highlighted. Other AEDs, and notes on polypharmacy, will be included in the second part of this series. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Effects of the human antiepileptic drug carbamazepine on the behavior, biomarkers, and heat shock proteins in the Asian clam Corbicula fluminea.

    Science.gov (United States)

    Chen, Huihui; Zha, Jinmiao; Liang, Xuefang; Li, Jiasu; Wang, Zijian

    2014-10-01

    Carbamazepine (CBZ), an anticonvulsant and mood-stabilizing pharmaceutical, is a widespread contaminant in aquatic environments. In this study, the effects of chronic exposure to environmentally relevant CBZ concentrations were investigated in freshwater clams Corbicula fluminea. Adult C. fluminea were exposed to 0.5, 5, and 50 μg/L of CBZ for 30 days, after which siphoning behavior (filtration rates), biomarker levels, and heat shock protein expression were measured. The filtration rates were significantly decreased (pfluminea health. Superoxide dismutase (SOD) and glutathione reductase (GR) activities were decreased, and catalase (CAT) activity and malondialdehyde (MDA) content were increased in the gills and digestive gland, suggesting that CBZ induced an oxidative effect. The levels of Hsp22, Hsp40, and Hsp70 mRNAs were also markedly induced after 5 or 50 μg/L CBZ treatment (pfluminea tissue at the molecular and protein level. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Oxidative stress is increased in women with epilepsy: Is it a potential mechanism of anti-epileptic drug-induced teratogenesis?

    Directory of Open Access Journals (Sweden)

    Damayanthi Deepa

    2012-01-01

    Full Text Available Context: Oxidative stress can be a final common pathway for AED-induced teratogenesis. Aims: To compare the oxidative stress of women with epilepsy (WWE and unfavorable pregnancy outcome (fetal malformation or spontaneous abortion - group EM with that of WWE with normal pregnancy outcome (group ENM and healthy women with normal pregnancy outcome (group C. Materials and Methods: We identified WWE under group EM (n = 43 and group ENM (n = 22 from the Kerala Registry of Epilepsy and Pregnancy (KREP. Group C was constituted of healthy volunteers (N = 20. Oxidative stress was assessed by estimating serum levels of malondialdehyde (MDA and isoprostane (ISP. The antioxidant profile was evaluated as activity of superoxide dismutase (SOD, glutathione reductase (GR, catalase (CAT, total antioxidant status (TAO, and glutathione (GSH content. Results: The MDA and ISP levels for group EM (3.46 + 0.82 and 17.77 + 3.0 were higher than that of group ENM (3.07 + 1.02 and 14.0 + 5.3, and both were significantly higher than that of group C (2.42 + 0.51 and 10.77 + 4.1. Their levels of SOD (146.82 + 42.64 vs. 175.81 + 42.61 and GSH (0.98 + 0.98 vs. 1.55 + 1.3 were significantly lower than those of controls. No significant changes were seen in TAO and GR. WWE on polytherapy showed significant increase in MDA when compared to monotherapy group. Conclusion: WWE (group EM and ENM had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with unfavorable pregnancy outcome (group EM had higher oxidative stress. Excess oxidative stress can be a final common pathway, by which AEDs exert teratogenic effects.

  4. Drug Facts

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    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath ... Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  5. Drug Facts

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    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  6. Drug Facts

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    Full Text Available ... Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Information about this page Click on the button that says "Listen" on any page and the computer will read the text to you. This website talks ...

  7. Identifying Drugs

    Science.gov (United States)

    ... and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and Recovery Federal Student Aid and Consequences of a Drug Conviction School Failure VIDEO: Taking Prescription Drugs to Get High—A Bad Idea Drugged Driving—What You Should Know How ...

  8. ASSOCIATION BETWEEN CARBAMAZEPINE INDUCED SEVERE CUTANEOUS ADVERSE DRUG REACTION AND HLA POLIMORPHISMS

    Directory of Open Access Journals (Sweden)

    Safrina Dewi Ratnaningrum

    2016-01-01

    Full Text Available Carbamazepine as an antiepileptic drug that is used widely and was known can cause severe cutaneous adverse drug reactions like SJS-TEN. These adverse drug reactions is known to be associated with some specific HLA polymorphism in European populations (HLA-A*31: 01, China (HLA-A*31: 01; HLA-B*15:02, Japan (HLA-A*31 : 01; HLA-B*15: 11, Korea HLA-A*31: 01; HLA-B*15: 02; HLA-B*15: 11, India (HLA-B*15:02, Thailand (HLA-B*15: 02, and Malaysia (HLA-B*15: 02. Information related to certain HLA polymorphism is important to prevent adverse drug reaction but there is no sufficient data on the population of Indonesia.

  9. 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

  10. Fluorescence And Alternative Methods In Urine Drug Testing

    Science.gov (United States)

    Jain, Naresh C.

    1988-04-01

    Drug abuse has become-one of the most compelling realities _ ot contemporary society. It has penetrated every segment ot our population: trom schools to sports and trom organized crime to board rooms . Drugs in tie w9rkplace allegedly cost government agencies and business millions ot dollars each year in increased absenteeism,. poor work performance, thefts,accidents andwastedtime. The President's Commission on Organized Crime and the federal government are in tavor ot urine drug testing. In fact many employers are now resorting to urine drug testing on current and prospective employees. This presep.tation discusses different laboratory methods used in urine drug.testing, including immunoassays, fluorescence polarization, thin layer chromatography, high pressure liquid chromatography, gas chromatography and gas-chromatography-mass spectrometry.

  11. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with ... problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ...

  14. Drug Abuse

    Science.gov (United States)

    ... and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  16. Drug Facts

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    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes ... Options? What Is Recovery? What Is a Relapse? How Can Friends and Family Help? Where Can Someone ...

  18. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Drug metabolism may be defined as the biochemical modifica- tion of one chemical form to another, occurring usually through ..... Endogenous. Enzyme. Drugs. Cofactor. Glucuronidation. UDP glucoronic. UDP-. Chloramphenicol, acid glucuronosyltransferase morphine, paracetamol, salicylic acid, fenoprofen, desipramine,.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and ...

  20. Drug Facts

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    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  1. Study Drugs

    Science.gov (United States)

    ... What Are Study Drugs? Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit ... stimulants are used as study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  5. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs ... adicción. English Español About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  11. Drug Resistance

    Science.gov (United States)

    ... infected with a drug-resistant strain of HIV. Drug-resistance testing results are used to decide which HIV medicines to include in a person’s first HIV regimen. After treatment is started, drug-resistance testing is repeated if ...

  12. 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.

  13. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  14. 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

  15. WAr on DrugS

    African Journals Online (AJOL)

    2009-04-12

    Apr 12, 2009 ... tion of drugs, especially hemp (Cannabis. Sativa), became entrenched. Oloruntoba. (2006) explained that the vigour and sus- tained efforts to legislate against drugs in contemporary Nigeria was because of the growing notoriety of the country as a transit point or centre for recruitment of drug couriers, and a ...

  16. [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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Jan Henje Döring

    Full Text Available 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.

  19. ILLICIT DOPAMINE TRANSIENTS: RECONCILING ACTIONS OF ABUSED DRUGS

    Science.gov (United States)

    Covey, Dan P.; Roitman, Mitchell F.; Garris, Paul A.

    2014-01-01

    Phasic increases in brain dopamine are required for cue-directed reward seeking. While compelling within the framework of appetitive behavior, the view that illicit drugs hijack reward circuits by hyper-activating these dopamine transients is inconsistent with established psychostimulant pharmacology. However, recent work reclassifying amphetamine (AMPH), cocaine, and other addictive dopamine-transporter inhibitors (DAT-Is) supports transient hyper-activation as a unifying hypothesis of abused drugs. We argue here that reclassification also identifies generating burst firing by dopamine neurons as a keystone action. Unlike natural rewards, which are processed by sensory systems, drugs act directly on the brain. Consequently, to mimic natural reward and exploit reward circuits, dopamine transients must be elicited de novo. Of available drug targets, only burst firing achieves this essential outcome. PMID:24656971

  20. [Efficacy and tolerability of carbamazepine as the initial drug used in the treatment of epilepsy].

    Science.gov (United States)

    Zubcević, Smail; Gavranović, Muhamed; Katica, V; Brajković, D; Catibusić, Feriha

    2002-01-01

    Carbamazepine is the one of the most prescribed antiepileptic drugs in treatment of partial and generalized tonic-clonic seizures. Its efficacy in treatment of seizures was discovered incidentally during the trials of neuroleptic drugs. Generally it is well tolerated with relatively rare serious side effects. Therapy is introduced gradually, with mean dose between 10-20 mg/kg, and given this way it has the least side effects. Aim of the study was to assess interaction between efficacy, tolerability and overall efficacy of the first prescribed drug, in this case carbamazepine, in the group of patients with partial seizures and generalized tonic-clonic seizures. Patients hospitalized at University Pediatric Hospital in Sarajevo with newly diagnosed epilepsy and started therapy with carbamazepine in period from 07.1999 to 07.2002 were investigated. There were 89 patients that fulfilled the criteria. In 29 patients seizures remitted after the introduction of therapy (32.58%). After the subsequent correction of therapy further 8 patients were seizure free. In total, drug was efficient as a monotherapy in 68 patients (76.40%). Other antiepileptic drugs or polytherapy with carbamazepine were tried in the patients that were not seizure free. Adverse effects were reported in 28 patients (31.46%). The most frequent was benign leucopoenia (16 patients, 17.97%) that did not require changes in therapy. Rash was found in 8 patients (8.98%), out of which in 6 therapy had to be stopped. Compliance with therapeutic regime was slightly better with controlled release formulation (89.98%) then with simplex formulation (77.52%), but generally was good. We think that carbamazepine is still the drug of the first choice in treatment of patients with partial epileptic seizures and generalized tonic-clonic seizures. It showed good overall efficacy with relatively rare serious side effects.

  1. [NEPHROTOXIC DRUGS].

    Science.gov (United States)

    Popović, B; Šutić, I; Marković, N Bašić

    2016-12-01

    Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

  2. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  3. Lack of drug preparations for use in children in Brazil.

    Science.gov (United States)

    Costa, Patrícia Quirino da; Rey, Luis C; Coelho, Helena Lutéscia L

    2009-01-01

    To identify drugs which are not suited for pediatric use in Brazil. A descriptive study involving the development of a national list of unlicensed and off-label medications for pediatric use (problem drugs in pediatrics, PDP) through a literature review, a comparison among sources of the Brazilian pharmaceutical industry, and a survey with pediatricians. Drugs coded at the Anatomic Therapeutic Chemical (ATC) Classification System were analyzed regarding licensing status in Brazil and recommendations/indications in pediatrics, based on the following reference sources: the list of licensed drugs of the Brazilian National Health Surveillance Agency (2005), the Brazilian Dictionary of Pharmaceutical Specialties (2005-2007) and the website www.bulas.med.br. Our literature search returned 126 PDP, but 24 drugs were excluded due to absence of national reference. To compose the final list, 24 other drugs referred by pediatricians were added. Of the 126 PDP, 23 drugs were not licensed in the country for use in children; and of the 103 licensed drugs, 24 presented age-related restrictions for pediatric use. The pharmaceutical list included 42 therapeutic groups and 68 subgroups. The groups containing larger numbers of PDP were: antibiotics for systemic use (15), antiepileptics (8), antiasthmatics (7), and analgesics (7). The most frequent problems were: inappropriate dosage (35), unlicensed for pediatric use (28), age-related restrictions (23). The lack of pediatric drug formulations in Brazil shows a profile similar to that observed in other countries, which involves a wide range of clinically important products. This study brings a contribution to the evaluation of the needs and priorities that support the development of suitable medicines for the pediatric patient.

  4. [Orphan drugs].

    Science.gov (United States)

    Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

    2013-01-01

    Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.

  5. AIDSinfo Drug Database

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content Drugs Home Drugs Find information on FDA-approved HIV/ ... infection drugs and investigational HIV/AIDS drugs. Search Drugs Search drug Search Icon What's this? Close Popup ...

  6. No signal of interactions between influenza vaccines and drugs used for chronic diseases: a case-by-case analysis of the vaccine adverse event reporting system and vigibase.

    Science.gov (United States)

    Carnovale, Carla; Raschi, Emanuel; Leonardi, Luca; Moretti, Ugo; De Ponti, Fabrizio; Gentili, Marta; Pozzi, Marco; Clementi, Emilio; Poluzzi, Elisabetta; Radice, Sonia

    2018-03-09

    An increasing number of reports indicates that vaccines against influenza may interact with specific drugs via drug metabolism. To date, actual impact of vaccine-drug interactions observed in the real world clinical practice has not been investigated. From VAERS and VigiBase, we collected Adverse Event Following Immunization (AEFI) reports for individuals receiving vaccines against influenza recorded as suspect and selected cases where predictable toxicity was recorded with oral anticoagulants, antiepileptics and statins (i.e. hemorrhages, overdosage and rhabdomyolysis, respectively). We applied AEFI and Drug Interaction Probability Scale (DIPS) Algorithms to assess causality of drug-vaccine interactions. 116 AEFI reports submitted to VAERS and 83 from Vigibase were included in our analysis; antiepileptics and statins were related to the highest number of indeterminate/consistent (93.7%; 65.3%) and possible/probable (50%; 57.7%) cases according to the AEFI and DIPS, respectively. The majority of cases occurred within the first week after vaccine administration (5-7 days). The relative paucity of detected interactions does not impact on the benefit of the vaccination against influenza, which remains strongly recommended; this does not exclude that closer monitoring for selected patients exposed to concomitant chronic pharmacological therapies and affected by predisposing factors may be useful.

  7. Drug Facts

    Medline Plus

    Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

  8. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  9. Drug Facts

    Medline Plus

    Full Text Available ... Say if You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button that says "Listen" on any page and the computer will read the ... Videos Information About ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often ... NIH is a component of the U.S. Department of Health and Human Services . PDF documents require the free Adobe Reader . ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

  12. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    Chemistry of Drug Metabolism. Drug metabolism is a chemical process, where enzymes play a crucial role in the conversion of one chemical species to another. The major family of enzymes associated with these metabolic reactions is the cytochrome P450 family. The structural features and functional activity of these ...

  13. Drugged Driving

    Science.gov (United States)

    ... Survey Results Synthetic Cannabinoids (K2/Spice) Unpredictable Danger Drug and Alcohol Use in College-Age Adults in 2016 Monitoring the Future 2016 Survey Results Drug and Alcohol Use in College-Age Adults in 2015 View All NIDA Home ...

  14. Capping Drugs

    Indian Academy of Sciences (India)

    In the process of treatment, drugs are also used for medical diagnosis and for ... ing cells. Since cancer cells grow at a faster rate than the normal .... ity characteristics. After intake, the N-methyl group is cleaved in the liver to release the physiologically active drug. Similarly, membrane transportation characteristics of the neu-.

  15. Antiepileptic properties of novel 2-(substituted benzylidene-7-(4-chlorophenyl-5-(furan-2-yl-2H-thiazolo[3,2-a]pyrimidin-3(7H-one derivatives

    Directory of Open Access Journals (Sweden)

    Visvanathen Karthick

    2016-09-01

    Full Text Available In the present study, a series of novel 2-(substituted benzylidene-7-(4-chlorophenyl-5-(furan-2-yl-2H-thiazolo[3,2-a]pyrimidin-3(7H-one derivatives (4a–i were designed and synthesized to meet the structural requirements essential for antiepileptic activity. Antiepileptic screening was performed by maximal electroshock (MES and subcutaneous pentylenetetrazole (scPTZ seizures tests and neurotoxicity was determined by the rotorod test. Among the synthesized compounds 4f, 4g and 4h were found active in both MES and scPTZ models. In the view of results the most active compounds carry fluoro > chloro > bromo substituent’s at the para position in the phenyl ring. The chemical structures of the synthesized compounds were confirmed by means of IR, 1H NMR, mass spectroscopy and elemental analysis.

  16. Sexual dysfunction related to psychotropic drugs: a critical review. Part III: mood stabilizers and anxiolytic drugs.

    Science.gov (United States)

    La Torre, A; Giupponi, G; Duffy, D M; Pompili, M; Grözinger, M; Kapfhammer, H P; Conca, A

    2014-01-01

    Sexual dysfunction is a potential side effect of mood stabilizers and anxiolytic drugs: this article presents a critical review of the current literature. Although many studies have been published on sexual side effects of psychopharmacological treatment, only a minority relate to mood stabilizers and anxiolytic drugs. Most of these studies are not methodologically robust, few are RCTs and most did not use a validated rating scale to evaluate sexual functioning. In addition, many of the studies on sexual dysfunction associated with mood stabilizers and anxiolytic drugs are limited by other methodological flaws. While there is evidence to suggest that mood stabilizers, with some exceptions, negatively affect sexual functioning, there is still insufficient evidence to draw any clear conclusions about the effects of anxiolytic drugs on sexual function. There is some weak evidence to indicate that switching from enzyme-inducing to non-enzyme-inducing anticonvulsant drugs, could be clinically useful. Some researchers recommend that sexual dysfunction in patients taking antiepileptic drugs should in general be treated according to standard guidelines for the management of sexual dysfunction, since reliable data on special populations is not available. However, specific approaches may be useful, but cannot yet be recommended until further validating research has been conducted. We did not find evidence supporting the use of any specific treatment strategy for sexual dysfunction associated with anxiolytic treatment. This study was conducted in 2013 using the paper and electronic resources of the library of the Azienda Provinciale per i Servizi Sanitari (APSS) in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane Library, Micromedex healthcare series, BMJ Clinical Evidence. The full list of available journals can be viewed at http

  17. Drug-induced angioedema: experience of Italian emergency departments.

    Science.gov (United States)

    Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F

    2014-06-01

    Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

  18. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  19. Telling a Compelling Tale, Scientifically Speaking

    Science.gov (United States)

    Unger, M.; Hauser, R.; Backlund, P.

    2009-12-01

    We will examine three strategies for conveying science effectively to a broad audience: making science relevant, accessible, and intriguing. Through an analysis of the dissemination strategy for three research-related stories at the National Center for Atmospheric Research, we explore methods for successful communication of societally relevant science. We will discuss both time-honored and new means of conveying authentic science in a rapidly changing media landscape. This visualization from the Hayden Planetarium's Journey to the Stars shows the generation of magnetic field in the solar convection zone and its connection to a sunspot at the visible surface of the Sun. Note that the sunspot (with a size slightly larger than Earth) is enlarged for better visibility and not in proper scale relative to the Sun. (© 2009, American Museum of Natural History) New research shows that the Arctic reversed a long-term cooling trend and began warming rapidly in recent decades. The graph shows estimates of Arctic temperatures over the last 2,000 years, based on proxy records, the long-term cooling trend, and the recent warming based on actual observations. A 2000-year transient climate simulation with NCAR's Community Climate System Model shows the same overall temperature decrease as does the proxy temperature reconstruction, which gives scientists confidence that their estimates are accurate.

  20. Accurate Assessment--Compelling Evidence for Practice

    Science.gov (United States)

    Flynn, Regina T.; Anderson, Ludmila; Martin, Nancy R.

    2010-01-01

    Childhood overweight and obesity is a public health concern not just because of its growing prevalence but also for its serious and lasting health consequences. Though height and weight measures are easy to obtain and New Hampshire Head Start sites measure height and weight of their enrollees, there are numerous challenges related to accurate…

  1. Energy plight compels ingenuity in Israel

    Energy Technology Data Exchange (ETDEWEB)

    Bardin, D.J.

    1981-09-01

    The second in a series of invited papers on energy in foreign countries describes Israel's energy program in terms of its political and military position in the Arab oil-producing world. As a holdover of British colonialism, Israel uses expensive oil imports as its primary fuel, making the country dependent on imports of 95% of primary fuels compared to the US's 20%. A review of Israeli history since independence parallels the development of the nation's energy philosophy and policy as a lesson in meeting adversity with a positive attitude. Israel is using its technological flexibility and business ingenuity to stockpile oil, encourage solar energy use and conservation, plan for coal substitution, and explore the possibilities of hydro, nuclear, oil shale, peat, and other options. (DCK)

  2. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  3. 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

  4. Current perspectives on intrathecal drug delivery

    Directory of Open Access Journals (Sweden)

    Bottros MM

    2014-11-01

    Full Text Available Michael M Bottros,1 Paul J Christo2 1Division of Pain Medicine, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, 2Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. Keywords: pain control, intrathecal analgesia, drug delivery systems

  5. Drug resistance in cortical and hippocampal slices from resected tissue of epilepsy patients: no significant impact of P-glycoprotein and Multidrug resistance associated proteins.

    Directory of Open Access Journals (Sweden)

    Nora eSandow

    2015-02-01

    Full Text Available Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp and multidrug resistance associated proteins (MRPs expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs (carbamazepine, sodium valproate, phenytoin and two unspecific inhibitors of Pgp and MRPs (verapamil and probenecid on seizure-like events induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices were studied. Although in slice preparations the blood brain barrier is not functional, we found that seizure-like events predominantly persisted in the presence of anticonvulsant drugs (90% and also in the presence of verapamil and probenecid (86%. Following subsequent co-administration of antiepileptic drugs and drug transport inhibitors, seizure-like events continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30% or as suppression (7%, particularly by perfusion with carbamazepine in probenecid containing solutions (43%, 9%. Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7 % of patients. Patients whose tissue was completely or partially sensitive (65 % presented with higher seizure frequencies than those with resistant tissue (35 %. However, corresponding subgroups of patients don’t differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue.

  6. Drug Facts

    Science.gov (United States)

    ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  7. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain ... About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... changes in her life. She finds support from family and friends who don't use marijuana. Haga ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... prescription drugs. The addiction slowly took over his life. I need different people around me. To stop ... marijuana, "Cristina" is making positive changes in her life. She finds support from family and friends who ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  18. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.

    Science.gov (United States)

    Geffrey, Alexandra L; Pollack, Sarah F; Bruno, Patricia L; Thiele, Elizabeth A

    2015-08-01

    Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article. Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored. We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [-2-91%] at 4 weeks); the mean increase in nCLB levels was 500 ± 300% (95% CI [+90-610%] at 4 weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction. Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  19. 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

  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. Harm to patients and others caused by impaired junior doctors compelled to work 30-hour shifts or longer: Can the minister of health, provincial MECs for health and public health officials be held liable?

    Directory of Open Access Journals (Sweden)

    David Jan McQuoid-Mason

    2016-11-01

    Full Text Available Junior doctors in most provinces in South Africa are compelled to work 30-hour shifts without a break. Shifts in excess of 24 hours can result in serious bodily harm to patients, third parties and the doctors themselves. These risks have been drawn to the attention of the health authorities but the 30-hour policy continues to be implemented in all provinces, except recently in the Western Cape. Public health officials may be held directly liable for the harm caused to patients, third parties or the junior doctors themselves, if it can be shown that they are at fault and are acting unlawfully in violation of the Constitution. Where officials carry out the unlawful orders of senior officials, including the minister of health and provincial members of the executive council (MECs for health, they may not raise the defence of ‘obedience to orders’ and may be held directly liable for harm caused. Superior officials issuing such orders will also be held directly liable for harm caused.

  2. It Is Not That Simple nor Compelling!; Comment on “Translating Evidence Into Healthcare Policy and Practice: Single Versus Multi-faceted Implementation Strategies – Is There a Simple Answer to a Complex Question?”

    Directory of Open Access Journals (Sweden)

    Tracey Bucknall

    2015-11-01

    Full Text Available Healthcare decisions are often made under pressure, with varying levels of information in a changing clinical context. With limited resources and a focus on improving patient outcomes, healthcare managers and health professionals strive to implement both clinical and cost-effective care. However, the gap between research evidence and health policy/clinical practice persists despite our best efforts. In an attempt to close the gap through behaviour change interventions, there has been a strong held belief that ‘more is better,’ without understanding the mechanisms and circumstances of knowledge translation (KT. We argue that even a singleintervention or strategy in translating evidence into healthcare policy or practice is rarely simple to implement. Nor is the evidence compelling on the best approach. As Harvey and Kitson argued, designing and evaluating KT interventions requires flexibility and responsiveness. If we are to move forward in translation science then we need to use rigorous designs such as randomised controlled trials to test effectiveness of interventions or strategies with embedded process evaluations to understand the reason interventions do or do not work!

  3. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  4. [Drug promiscuity].

    Science.gov (United States)

    Guo, Zong-ru

    2011-04-01

    It is essential for a successful drug to possess two basic characteristics: satisfactory pharmacological action with sufficient potency and selectivity; good druggability with eligible physicochemical, pharmacokinetic and safety profiles, as well as structural novelty. Promiscuity is defined as the property of a drug to act with multiple molecular targets and exhibit distinct pharmacological effects. Promiscuous drugs are the basis of polypharmacology and the causes for side effects and unsuitable DMPK. Drug promiscuity originates from protein promiscuity. In order to accommodate, metabolize and excrete various endo- and exogenous substances, protein acquired the capability during evolution to adapt a wide range of structural diversity, and it is unnecessary to reserve a specific protein for every single ligand. The structures of target proteins are integration of conservativity and diversity. The former is represented by the relatively conservative domains for secondary structures folding, which leads to overlapping in ligand-binding and consequent cross-reactivity of ligands. Diversity, however, embodies the subtle difference in structures. Similar structural domain may demonstrate different functions due to alteration of amino acid sequences. The phenomenon of promiscuity may facilitate the "design in" of multi-target ligands for the treatment of complicated diseases, whereas it should be appropriately handled to improve druggability. Therefore, one of the primary goals in drug design is to scrutinize and manipulate the "merits and faults" of promiscuity. This review discusses the application of promiscuity in drug design for receptors, enzymes, ion channels and cytochrome P450. It also briefly describes the methods to predict ligand promiscuity based on either target or ligand structures.

  5. [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.

  6. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  7. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  8. Expression pattern of NMDA receptors reveals antiepileptic potential of apigenin 8-C-glucoside and chlorogenic acid in pilocarpine induced epileptic mice.

    Science.gov (United States)

    Aseervatham, G Smilin Bell; Suryakala, U; Doulethunisha; Sundaram, S; Bose, P Chandra; Sivasudha, T

    2016-08-01

    The present study was aimed to evaluate the effect of apigenin 8-C-glucoside (Vitexin) and chlorogenic acid on epileptic mice induced by pilocarpine and explored its possible mechanisms. Intraperitonial administration of pilocarpine (85mg/kg) induced seizure in mice was assessed by behavior observations, which is significantly (p>0.05) reduced by apigenin 8-C-glucoside (AP8CG) (10mg/kg) and chlorogenic acid (CA) (5mg/kg), similar to diazepam. Seizure was accompanied by an imbalance in the levels of Gamma-aminobutyric acid (GABA) and glutamate in the pilocarpine administered group. Moreover, convulsion along with reduced acetylcholinesterase, increased monoamine oxidase and oxidative stress was observed in epileptic mice brain. AP8CG and CA significantly restored back to normal levels even at lower doses. Further, increased lipid peroxidation and nitrite content was also significantly attenuated by AP8CG and CA. However, CA was found to be more effective when compared to AP8CG. In addition, the mRNA expression of N-methyl-d-aspartate receptor (NMDAR), mGluR1 and mGlu5 was significantly (P≤0.05) inhibited by AP8CG and CA in a lower dose. The mRNA expression of GRIK1 did not differ significantly in any of the group and showed a similar pattern of expression. Our result shows that AP8CG and CA selectively inhibit NMDAR, mGluR1 and mGlu5 expression. Modification in the provoked NMDAR calcium response coupled with neuronal death. Hence, these findings underline that the polyphenolics, AP8CG and CA have exerted antiepileptic and neuroprotective activity by suppressing glutamate receptors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Drug Allergy

    African Journals Online (AJOL)

    EL-HAKIM

    Rasha H. El-Owaidy. Immunology Unit, Department of Pediatrics, Ain Shams University, Cairo. Introduction. Adverse reactions to pharmaceutical and diagnostic products constitute a major hazard in the practice of medicine and are responsible for substantial morbidity and cost. Adverse drug reactions can be divided into ...

  10. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure

  11. Capping Drugs

    Indian Academy of Sciences (India)

    It is well documented that till recent times drugs derived from plants were used to relieve patients from suffering. But at the turn of the last century, with the improvement in purification meth- ods using chromatographic techniques, single compounds with well-defined structure became available for testing and treat- ment.

  12. Drugs reviews

    African Journals Online (AJOL)

    Angel_D

    chlorpropamide] and biguanides [e.g. metformin]), steroids and dapsone. The effectiveness of these drugs is likely to be reduced. Side-effects are uncommon but include: ▫ Skin reactions: rash, urticaria, flushing. Fortunately many of these reactions are self-limiting and gradually clear; the patient only needs symptomatic ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  14. Misused Drug

    African Journals Online (AJOL)

    analgesic effects by antagonising a subset of glutamate receptors ... unpleasant dreams up to 24hrs after the drug has been given.7 ... are intact. The amnesic effect of ketamine, which often persists for up to one hour after recovery of consciousness, cnsuree that there is no recall of surgery or anaesthesia. Effects on the War ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  16. Drugged Driving

    Science.gov (United States)

    ... Pain Prevention Recovery Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications ... mind-altering ingredient, in the blood. But the role that marijuana plays in crashes is ... age, gender, race, and presence of alcohol. 9 More research ...

  17. Prescription Drugs

    Science.gov (United States)

    ... Future survey shows long term decline in illicit drug use, prescription opioid abuse, cigarette and alcohol use among the nation’s youth. View Online Download PDF Monitoring the Future 2013 Survey Results: College and Adults Published: April 30, 2015 In 2013, ...

  18. Drug enhancement of memory consolidation: historical perspective and neurobiological implications.

    Science.gov (United States)

    McGaugh, James L; Roozendaal, Benno

    2009-01-01

    Studies of drug enhancement of cognition began with Lashley's (Psychobiology 1:141-170, 1917) report that strychnine administered before daily training trials enhanced rats' maze learning. Many subsequent studies confirmed that finding and found that stimulant drugs also enhance the learning of a wide range of tasks. A central problem in interpreting such findings is that of distinguishing the drug effects on brain processes underlying memory formation from many other possible effects of the drugs on the behavior used to assess learning. The subsequent finding that comparable learning enhancement can be obtained by posttraining drug administration provided compelling evidence that drugs can enhance memory by acting on memory consolidation processes. Such evidence stimulated the investigation of endogenous regulation of memory consolidation by arousal-released adrenal stress hormones. Considerable evidence now indicates that such hormones regulate memory consolidation via activation of the basolateral amygdala and subsequent influences on many efferent brain regions involved in processing recent experiences. The implications of these findings for the development of cognitive enhancing drugs are discussed.

  19. Generic - equivalent drugs use in internal and general medicine patients: distrust, confusion, lack of certainties or knowledge? Part 1. Pharmacological issues

    Directory of Open Access Journals (Sweden)

    Roberto Nardi

    2014-05-01

    Full Text Available Despite compelling evidence and guidelines, in Italy, generic/equivalent drugs are still underused. The failure to adopt existing generic drugs may result into a missed opportunity to further reduce healthcare costs. Equivalent drugs are approved based on data deriving from bioequivalence studies. In the first part of the article, the concepts of generic/equivalent drugs are defined, emphasizing the differences between pharmaceutical equivalence, therapeutic equivalence, bioequivalence and bioavailability. A summary of the methods adopted to define bioequivalence (pharmacokinetic studies; pharmacodynamic studies; comparative clinical trials; in vitro studies is also included.

  20. Drug abuse first aid

    Science.gov (United States)

    ... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

  1. 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.

  2. Policing, massive street drug testing and poly-substance use chaos in Georgia - a policy case study.

    Science.gov (United States)

    Otiashvili, David; Tabatadze, Mzia; Balanchivadze, Nino; Kirtadze, Irma

    2016-01-16

    Since early 2000, intensive policing, wide scale street drug testing, and actions aimed at limiting the availability of specific drugs have been implemented in Georgia. Supporters of this approach argue that fear of drug testing and resulting punishment compels drug users to stop using and prevents youth from initiating drug use. It has been also stated that reduction in the availability of specific drugs should be seen as an indication of the overall success of counter-drug efforts. The aim of the current review is to describe the drug-related law enforcement response in Georgia and its impact on illicit drug consumption and drug-related harm. We reviewed relevant literature that included peer-reviewed scientific articles, stand-alone research reports, annual drug situation reports, technical reports and program data. This was also supplemented by the review of relevant legislation and judicial practices for the twelve year period between 2002 and 2014. Every episode of reduced availability of any "traditional" injection drug was followed by the discovery/introduction of a new injection preparation. The pattern of drug consumption was normally driven by users' attempts to substitute their drug of choice through mixing together available alternative substances. Chaotic poly-substance use and extensive utilization of home-made injection drugs, prepared from toxic precursors, became common. Massive random street drug testing had little or no effect on the prevalence of problem drug use. Intensive harassment of drug users and exclusive focus on reducing the availability of specific drugs did not result in reduction of the prevalence of injecting drug use. Repressive response of Georgian anti-drug authorities relied heavily on consumer sanctions, which led to shifts in drug users' behavior. In most cases, these shifts were associated with the introduction and use of new toxic preparations and subsequent harm to the physical and mental health of drug consumers.

  3. Cutaneous Adverse Drug Reactions to Lamotrigine and Human Leukocyte Antigen Typing in North Indian Patients: A Case Series.

    Science.gov (United States)

    Srivastava, Shivani; Ramanujam, Bhargavi; Ihtisham, Kavish; Tripathi, Manjari

    2017-01-01

    Cutaneous adverse drug reaction (cADR) has limited epidemiological data in India. The older antiepileptic drugs, i.e., carbamazepine, phenytoin, valproic acid, phenobarbitone, etc., induce severe cADRs that have a strong associated with human leukocyte antigen (HLA)-related genetic risk factors. There is also evidence of association of certain HLA alleles with lamotrigine (LTG)-induced cADRs, but this has not been reported in the Indian population. Here, we report case series of three patients with LTG-induced "Stevens-Johnson syndrome (SJS)." Their HLA-B typing was also performed which showed the presence of HLA-B*15:02 in one case with SJS.

  4. Activity Clamp Provides Insights into Paradoxical Effects of the Anti-Seizure Drug Carbamazepine.

    Science.gov (United States)

    Morris, Gareth; Leite, Marco; Kullmann, Dimitri M; Pavlov, Ivan; Schorge, Stephanie; Lignani, Gabriele

    2017-05-31

    A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it is unclear why carbamazepine (CBZ), a frontline AED with a known molecular mechanism, has been reported to increase epileptiform activity in several clinical and experimental studies. We confirmed in an in vitro mouse model (in both sexes) that the frequency of interictal bursts increased after CBZ perfusion. To address the underlying mechanisms, we developed a method, activity clamp, to distinguish the response of individual neurons from network-level actions of CBZ. We first recorded barrages of synaptic conductances from neurons during epileptiform activity and then replayed them in pharmacologically isolated neurons under control conditions and in the presence of CBZ. CBZ consistently decreased the reliability of the second action potential in each burst of activity. Conventional current-clamp recordings using excitatory ramp or square-step current injections failed to reveal this effect. Network modeling showed that a CBZ-induced decrease of neuron recruitment during epileptic bursts can lead to an increase in burst frequency at the network level by reducing the refractoriness of excitatory transmission. By combining activity clamp with computer simulations, the present study provides a potential explanation for the paradoxical effects of CBZ on epileptiform activity. SIGNIFICANCE STATEMENT The effects of anti-epileptic drugs on individual neurons are difficult to separate from their network-level actions. Although carbamazepine (CBZ) has a known anti-epileptic mechanism, paradoxically, it has also been reported to increase epileptiform activity in clinical and experimental studies. To investigate this paradox during realistic neuronal epileptiform activity, we developed a method, activity clamp, to distinguish the effects of CBZ on individual neurons from network

  5. On the slow diffusion of Point of Care systems in Therapeutic Drug Monitoring

    Directory of Open Access Journals (Sweden)

    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. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza

    2010-05-01

    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  7. Urine drug screen

    Science.gov (United States)

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  8. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  9. Other Drugs of Abuse

    Science.gov (United States)

    ... People Abuse » Other Drugs of Abuse Other Drugs of Abuse Listen There are many other drugs of abuse, ... and Rehab Resources About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | Contact ...

  10. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  11. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  12. 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.

  13. Drug interaction between erlotinib and phenytoin for brain metastases in a patient with nonsmall cell lung cancer.

    Science.gov (United States)

    Ohgami, Masahiro; Kaburagi, Takayuki; Kurosawa, Atsuhiko; Homma, Masato

    2016-11-01

    Erlotinib, a substrate drug metabolized by the CYP3A4 enzyme, is an epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall cell lung cancer (NSCLC). Concomitant use of erlotinib and the antiepileptic drug phenytoin, an inducer of CYP3A4, may result in a drug-drug interaction accompanied by changes in the blood concentrations of both drugs. We determined the blood concentration of each drug to confirm the interaction between phenytoin and erlotinib in a case of NSCLC with brain metastases. The phenytoin blood concentration (8.2-10.0μg/mL) gradually increased 3-fold (to 24.2μg/mL) 7 months after the start of erlotinib (150mg/d) co-administration. The erlotinib blood concentration which was maintained at 0.15-0.37μg/mL under phenytoin co-administration, increased 12-fold (to 1.77μg/mL) after the stoppage of phenytoin co-administration. The present case revealed that blood phenytoin increased and blood erlotinib decreased subsequent to the interaction of the 2 drugs in the CYP3A4 metabolic enzyme system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. CONCEPT OF DRUG INTERACTION

    OpenAIRE

    Singh Nidhi

    2012-01-01

    Drug interaction is an increasingly important cause of adverse reactions (ADR), and is the modification of the effect of one drug (object) by the prior or concomitant administration of another drug (precipitant drug). Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin) are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or act...

  15. Understanding drugs and behaviour

    National Research Council Canada - National Science Library

    Parrott, Andrew

    2004-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix xi Part I Drugs and Their Actions . . . . . . . . . . . . . . . . . . . . . . 1 Psychoactive drugs: introduction and overview . . . . . . . . 2 The brain...

  16. Drug abuse

    International Nuclear Information System (INIS)

    Simon, T.R.; Seastrunk, J.W.; Malone, G.; Knesevich, M.A.; Hickey, D.C.

    1991-01-01

    This paper reports that this study used SPECT to examine patients who have abused drugs to determine whether SPECT could identify abnormalities and whether these findings have clinical importance. Fifteen patients with a history of substance abuse (eight with cocaine, six with amphetamine, and one with organic solvent) underwent SPECT performed with a triple-headed camera and Tc-99m HMPAO both early for blood flow and later for functional information. These images were then processed into a 3D videotaped display used in group therapy. All 15 patients had multiple areas of decreased tracer uptake peppered throughout the cortex but mainly affecting the parietal lobes, expect for the organic solvent abuser who had a large parietal defect. The videotapes were subjectively described by a therapist as an exceptional tool that countered patient denial of physical damage from substance abuse. Statistical studies of recidivism between groups is under way

  17. Drugs and the Brain.

    Science.gov (United States)

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  18. Serotonin2C receptors and drug addiction: focus on cocaine.

    Science.gov (United States)

    Devroye, Céline; Filip, Malgorzata; Przegaliński, Edmund; McCreary, Andrew C; Spampinato, Umberto

    2013-10-01

    This review provides an overview of the role of central serotonin2C (5-HT2C) receptors in drug addiction, specifically focusing on their impact on the neurochemical and behavioral effects of cocaine, one of the most worldwide abused drug. First, we described the neurochemical and electrophysiological mechanisms underlying the interaction between 5-HT2C receptors and the mesocorticolimbic dopaminergic network, in keeping with the key role of this system in drug abuse and dependence. Thereafter, we focused on the role of 5-HT2C receptors in the effects of cocaine in various preclinical behavioral models used in drug addiction research, such as locomotor hyperactivity, locomotor sensitization, drug discrimination, and self-administration, to end with an overview of the neurochemical mechanisms underlying the interactions between 5-HT2C receptors, mesocorticolimbic dopamine system, and cocaine. On their whole, the presented data provide compelling preclinical evidence that 5-HT2C receptor agonists may have efficacy in the treatment of cocaine abuse and dependence, thereby underlying the need for additional clinical studies to ascertain whether preclinical data translate to the human.

  19. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

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

    Directory of Open Access Journals (Sweden)

    Marzena Ułamek-Kozioł

    2016-09-01

    Full Text Available 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