WorldWideScience

Sample records for antiepileptic drugs compelling

  1. Antiepileptic drug hypersensitivity syndrome.

    Science.gov (United States)

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS 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 incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  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. Rational Polytherapy with Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Jong Woo Lee

    2010-07-01

    Full Text Available Approximately 30–40% of patients do not achieve seizure control with a single antiepileptic drug (AED. With the advent of multiple AEDs in the past 15 years, rational polytherapy, the goal of finding combinations of AEDs that have favorable characteristics, has become of greater importance. We review the theoretical considerations based on AED mechanism of action, animal models, human studies in this field, and the challenges in finding such optimal combinations. Several case scenarios are presented, illustrating examples of rational polytherapy.

  4. Antiepileptic drugs: newer targets and new drugs

    OpenAIRE

    Vihang S. Chawan; Abhishek M. Phatak; Kalpesh V. Gawand; Sagar V. Badwane; Sagar S. Panchal

    2016-01-01

    Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs), but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and...

  5. Advances in anti-epileptic drug testing.

    Science.gov (United States)

    Krasowski, Matthew D; McMillin, Gwendolyn A

    2014-09-25

    In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy. PMID:24925169

  6. Antiepileptic drugs: newer targets and new drugs

    Directory of Open Access Journals (Sweden)

    Vihang S. Chawan

    2016-06-01

    Full Text Available Epilepsy is a common neurological disorder affecting 0.5-1% of the population in India. Majority of patients respond to currently available antiepileptic drugs (AEDs, but a small percentage of patients have shown poor and inadequate response to AEDs in addition to various side effects and drug interactions while on therapy. Thus there is a need to develop more effective AEDs in drug resistant epilepsy which have a better safety profile with minimal adverse effects. The United States food and drug administration (USFDA has approved eslicarbazepine acetate, ezogabine, perampanel and brivaracetam which have shown a promising future as better AEDs and drugs like ganaxolone, intranasal diazepam, ICA- 105665, valnoctamide, VX-765, naluzotan are in the pipeline. [Int J Basic Clin Pharmacol 2016; 5(3.000: 587-592

  7. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.

    Science.gov (United States)

    Zaccara, Gaetano; Perucca, Emilio

    2014-12-01

    Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P-glycoprotein) and can reduce the efficacy of co-administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of

  8. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...

  9. 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....

  10. Effects of antiepileptic drugs in electrophysiological tests.

    Science.gov (United States)

    Rump, S; Kowalczyk, M

    1987-01-01

    Methods of the study of antiepileptic drugs activity by means of analysis of their effects on bioelectrical ictal phenomena in the animal brain are described. The paper deals especially with EEG signal processing methods. Application of various nonparametric models (e.g. interval-amplitude scatter plots, power spectra analysis) as well as parametric models (e.g. autoregressive model, segmentation analysis) is discussed. A discriminative approach to some of these methods (especially to autoregressive model) is also presented. Special attention is stressed on the value of these methods for the study of anticonvulsant drugs activity.

  11. Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies.

    Science.gov (United States)

    Mudigoudar, Basanagoud; Weatherspoon, Sarah; Wheless, James W

    2016-05-01

    The medical management of the epilepsy syndromes of early childhood (eg, infantile spasms, Dravet syndrome, and Lennox-Gastaut syndrome) is challenging; and requires careful evaluation, classification, and treatment. Pharmacologic therapy continues to be the mainstay of management for these children, and as such it is important for the clinician to be familiar with the role of new antiepileptic drugs. This article reports the clinical trial data and personal experience in treating the severe epilepsies of childhood with the recently Food and Drug Administration-approved new antiepileptic drugs (vigabatrin, rufinamide, perampanel, and clobazam) and those in clinical trials (cannabidiol, stiripentol, and fenfluramine). Genetic research has also identified an increasing number of pediatric developmental and seizure disorders that are possibly treatable with targeted drug therapies, focused on correcting underlying neural dysfunction. We highlight recent genetic advances, and how they affect our treatment of some of the genetic epilepsies, and speculate on the use of targeted genetic treatment (precision medicine) in the future. PMID:27544474

  12. Therapeutic drug monitoring of antiepileptic drugs by use of saliva.

    Science.gov (United States)

    Patsalos, Philip N; Berry, Dave J

    2013-02-01

    Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent. PMID:23288091

  13. Interactions between antiepileptic drugs and hormones.

    Science.gov (United States)

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

    2015-05-01

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

  14. [New antiepileptic drugs, and therapeutic considerations].

    Science.gov (United States)

    Szupera, Zoltán

    2011-09-30

    Epilepsy is not a singular disease, but a variety of disorders. It affects up to 0.5% of the population. Over the past decade, researchers have made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced to the market. Retigabine is a carbamic derivate, and its anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. Lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. Eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appear to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it will take the consideration of new concepts in shaping the new therapeutic algorithm. PMID:22059370

  15. Antiepileptic Drug Withdrawal in Dogs with Epilepsy.

    Science.gov (United States)

    Gesell, Felix Kaspar; Hoppe, Sonja; Löscher, Wolfgang; Tipold, Andrea

    2015-01-01

    Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs). In human beings with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free) for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases, the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects, and the idea that the medication could be unnecessary. Following AED withdrawal, four of these dogs remained seizure free, seven dogs suffered from seizure recurrence, of which only three dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication.

  16. Antiepileptic drug withdrawal in dogs with epilepsy

    Directory of Open Access Journals (Sweden)

    Felix Kaspar Gesell

    2015-08-01

    Full Text Available Epilepsy is one of the most common neurological disorders in dogs and is treated by chronic administration of antiepileptic drugs (AEDs. In humans with epilepsy, it is common clinical practice to consider drug withdrawal after a patient has been in remission (seizure free for three or more years, but withdrawal is associated with the risk of relapse. In the present study, the consequences of AED withdrawal were studied in dogs with epilepsy. Therefore, 200 owners of dogs with idiopathic or presumed idiopathic epilepsy were contacted by telephone interview, 138 cases could be enrolled. In 11 cases the therapy had been stopped after the dogs had become seizure free for a median time of 1 year. Reasons for AED withdrawal were appearance or fear of adverse side effects, financial aspects and the idea that the medication could be unnecessary. Following AED withdrawal, 4 of these dogs remained seizure free, 7 dogs suffered from seizure recurrence, of which only 3 dogs could regain seizure freedom after resuming AED therapy. Due to the restricted case number, an exact percentage of dogs with seizure recurrence after AED withdrawal cannot be given. However, the present study gives a hint that similar numbers as in human patients are found, and the data can help owners of epileptic dogs and the responsible clinician to decide when and why to stop antiepileptic medication.

  17. Chemical properties of antiepileptic drugs (AEDs).

    Science.gov (United States)

    Bialer, Meir

    2012-07-01

    Between 1990 and 2011 the following fifteen new antiepileptic drugs (AEDs) were approved: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. These AEDs (except felbamate) offer appreciable advantages in terms of their favorable pharmacokinetics, improved tolerability and lower potential for drug interactions. All AEDs introduced after 1990 that are not second generation drugs (with the exception of vigabatrin and tiagabine) were developed empirically (sometimes serendipitously) utilizing mechanism-unbiased anticonvulsant animal models. The empirical nature of the discovery of new AEDs in the last three decades coupled with their multiple mechanisms of action explains their diverse chemical structures. The availability of old and new AEDs with various activity spectra and different tolerability profiles enables clinicians to better tailor drug choice to the characteristics of individual patients. With fifteen new AEDs having entered the market in the past 20years the antiepileptic market is crowded. Consequently, epilepsy alone is not attractive in 2011 to the pharmaceutical industry even though the clinical need of refractory epilepsy remains unmet. Due to this situation, future design of new AEDs must also have a potential in non-epileptic CNS disorders such as neuropathic pain, migraine prophylaxis and bipolar disorder or fibromyalgia as demonstrated by the sales revenues of pregabalin, topiramate and valproic acid. This review analyzes the effect that the emerging knowledge on the chemical properties of the old AEDs starting from phenobarbital (1912) has had on the design of subsequent AEDs and new therapeutics as well as the current approach to AED discovery. PMID:22210279

  18. Cutaneous adverse drug reactions in dogs treated with antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Tina eKoch

    2016-04-01

    Full Text Available Epilepsy is one of the most common neurologic disorders in dogs and life-long treatment with antiepileptic drugs (AED is frequently required. Adverse events of antiepileptic drugs targeting the skin are only rarely reported in veterinary medicine and the true incidence and spectrum of cutaneous reactions in epileptic dogs remains unknown. In this study we hypothesized that cutaneous reactions commonly occur in epileptic dogs and are related to AED treatment. A retrospective case review of 185 dogs treated for epilepsy identified 20.0% with simultaneous appearance of dermatologic signs. In a subsequent prospective case investigation (n=137 we identified newly appearing or distinct worsening of skin lesions following initiation of antiepileptic drug therapy in 10.9% of dogs treated for epilepsy (95% CI 6.8- 17.7%. Cutaneous lesions were classified as probably drug-induced in 40.0% of these cases. Patch-testing and intradermal testing was further investigated as potential diagnostic methods to confirm antiepileptic drug hypersensitivity. They were of high specificity but sensitivity and positive predictive value appeared inappropriate to recommend their routine use in clinical practice.

  19. Sodium channels, inherited epilepsy, and antiepileptic drugs.

    Science.gov (United States)

    Catterall, William A

    2014-01-01

    Voltage-gated sodium channels initiate action potentials in brain neurons, mutations in sodium channels cause inherited forms of epilepsy, and sodium channel blockers-along with other classes of drugs-are used in therapy of epilepsy. A mammalian voltage-gated sodium channel is a complex containing a large, pore-forming α subunit and one or two smaller β subunits. Extensive structure-function studies have revealed many aspects of the molecular basis for sodium channel structure, and X-ray crystallography of ancestral bacterial sodium channels has given insight into their three-dimensional structure. Mutations in sodium channel α and β subunits are responsible for genetic epilepsy syndromes with a wide range of severity, including generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome, and benign familial neonatal-infantile seizures. These seizure syndromes are treated with antiepileptic drugs that offer differing degrees of success. The recent advances in understanding of disease mechanisms and sodium channel structure promise to yield improved therapeutic approaches. PMID:24392695

  20. Antiepileptic drug treatment strategies in neonatal epilepsy.

    Science.gov (United States)

    Hernan, A E; Holmes, G L

    2016-01-01

    The highest risk of seizures across the lifespan is in the neonatal period. The enhanced excitability of the immature brain compared to the mature brain is related to the sequential development and expression of essential neurotransmitter signaling pathways. During the neonatal period there is an overabundance of excitatory receptors, and γ-amino-butyric acid (GABA) is potentially depolarizing, as opposed to hyperpolarizing in the older brain. While this enhanced excitability is required for regulation of activity-dependent synapse formation and refining of synaptic connections that are necessary for normal brain development, enhanced excitability predisposes the immature brain to seizures. In addition to being common, neonatal seizures are very difficult to treat; antiepileptic drugs used in older children and adults are less efficacious, and possibly detrimental to brain development. In an effort to target the unique features of neurotransmission in the neonate, bumetanide, an NKCC1 inhibitor which reduces intraneuronal Cl(-) and induces a significant shift of EGABA toward more hyperpolarized values in vitro, has been used to treat neonatal seizures. As the understanding of the pathophysiology of genetic forms of neonatal epilepsy has evolved there have been a few successful attempts to pharmacologically target the mutated protein. This approach, while promising, is challenging due to the findings that the genetic syndromes presenting in infancy demonstrate genetic heterogeneity in regard to both the mutated gene and its function. PMID:27323943

  1. Antiepileptic Drugs in the Treatment of Anxiety Disorders

    OpenAIRE

    Levent Mete; Sinem Akyalcin; Pinar Cetinay Aydin

    2009-01-01

    In addition to epilepsy, antiepileptic drugs are used in neurologic conditions such as chronic pain and in the treatment of bipolar disorder in psychiatry. There are studies reporting its use in the treatment of anxiety disorders. The efficacy of antiepileptic drugs as carbamazepine, valproic asid, lamotrigine, topiramate, gabapentin, pregabalin in anxiety disorders has been shown in some clinical studies. The strongest evidence has been presented for pregabalin in generalized anxiety disorde...

  2. Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

    Directory of Open Access Journals (Sweden)

    Mustata Gabriela

    2011-06-01

    Full Text Available Abstract Background The present study compares antiepileptic drugs and aromatase (CYP19 inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs are needed, especially since every individual responds differently to given treatment options. Methods Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits. Results The pharmacophore model returned 73% (19 out of 26 of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62 of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses. Conclusions This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity

  3. Hypoactive sexual desire disorder caused by antiepileptic drugs

    OpenAIRE

    M Singh; Manish Bathla; Martin, A. (Alan); Aneja, J.

    2015-01-01

    Female sexual dysfunction is common but poorly understood sexual problem in women. Sexual dysfunction in female is multi-factorial in origin and also observed with intake of drug acting on central nervous system. This case report describes a female epileptic patient who developed sexual dysfunction with intake of antiepileptic drugs.

  4. Hypoactive sexual desire disorder caused by antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    M Singh

    2015-01-01

    Full Text Available Female sexual dysfunction is common but poorly understood sexual problem in women. Sexual dysfunction in female is multi-factorial in origin and also observed with intake of drug acting on central nervous system. This case report describes a female epileptic patient who developed sexual dysfunction with intake of antiepileptic drugs.

  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. Co-prescription of antiepileptic drugs and contraceptives

    NARCIS (Netherlands)

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

    2012-01-01

    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 prescripti

  7. Molecular Targets Versus Models for New Antiepileptic Drug Discovery

    OpenAIRE

    Rogawski, Michael A.

    2006-01-01

    Animal models have played a key role in the discovery and characterization of all marketed antiepileptic drugs (AED). The conventional wisdom is that the standard animal screening models are becoming obsolete because they fail to identify compounds that act in mechanistically new ways and as a result do not offer therapeutic advantages over presently available agents. In fact, far from only detecting me-too drugs, the models often uncover compounds with distinctive profiles of activity in var...

  8. Neurological and Psychiatric Sequelae of Developmental Exposure to Antiepileptic Drugs

    OpenAIRE

    KimfordMeador

    2012-01-01

    The neurons in the developing mammalian brain are susceptible to antiepileptic drug (AED) effects. It is known that later in life deficits in cognitive performance as well as psychiatric deficits can manifest after early AED exposure. The extent of these deficits will be addressed. This review will attempt to draw parallels between the existent animal models and human studies. Through analysis of these studies, important future research will be elucidated and possible new and emerging therapi...

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

    OpenAIRE

    Shahien, R.; K. Beiruti

    2012-01-01

    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 ...

  10. The New Antiepileptic Drugs: Their Neuropharmacology and Clinical Indications.

    Science.gov (United States)

    Hanaya, Ryosuke; Arita, Kazunori

    2016-05-15

    The administration of antiepileptic drugs (AEDs) is the first treatment of epilepsy, one of the most common neurological diseases. Therapeutic guidelines include newer AEDs as front-line drugs; monotherapy with new AEDs is delivered in Japan. While about 70% of patients obtain good seizure control by taking one to three AEDs, about 60% experience adverse effects and 33% have to change drugs. Compared to traditional AEDs, the prolonged administration of new AEDs elicits fewer adverse effects and fewer drug interactions and their teratogenicity may be lower. These characteristics increase drug compliance and allow combination therapy for drug-resistant epilepsy, although the antiepileptic effects of the new AEDs are not greater than of traditional AEDs. Comorbidities are not rare in epileptics; many adult patients present with stroke and brain tumors. In stroke patients requiring risk control and in chemotherapy-treated brain tumor patients, their fewer drug interactions render the new AEDs advantageous. Also, new AEDs offer favorable side benefits for concurrent diseases and conditions. Patients with stroke and traumatic brain injury often present with psychiatric/behavioral symptoms and cognitive impairment and some new AEDs alleviate such symptoms. This review presents an outline of the new AEDs used to treat adult patients based on the pharmacological activity of the drugs and discusses possible clinical indications from the perspective of underlying causative diseases and comorbidities. PMID:26935782

  11. [Influence of coadministered antiepileptic drugs on serum antiepileptic drug concentrations in epileptic patients -quantitative analysis based on suitable transforming factor].

    Science.gov (United States)

    Fukuoka, Noriyasu

    2004-07-01

    We conducted a study to clarify the most suitable transforming factor related to the daily dose of antiepileptic drugs (D) providing a steady-state serum concentration (C(t)) and analyzed the influences of the concomitant use of antiepileptic drugs on C(t) quantitatively. Data obtained by routine therapeutic drug monitoring from epileptic patients treated with the multiple oral administration of valproic acid (VPA), carbamazepine (CBZ), zonisamide (ZNS), phenobarbital (PB), and phenytoin (PHT) were used for the analysis. Employing the ideal body weight or the extracellular water volume as a transforming factor, allowed the level/dose (L/D) ratio to be independent of the patient's age and gender for monotherapy with VPA or CBZ, ZNS, PB, and PHT, respectively. Each C(t) was revealed to be dependent on only one variable in terms of the transformed daily dose (D'). C(t) was proportional to the power function of D' for VPA and CBZ and was linearly proportional to D' for ZNS and PB. The L/D ratio is expressed as a linear function of C(t) for PHT. For a detailed analysis of the influences of the coadministered antiepileptic drugs, we defined the parameter as an alteration ratio, representing the influence of each antiepileptic drug on the C(t) of VPA and CBZ alone, and on the L/D ratio of ZNS and PB alone, respectively. A model based on the assumption that each value of an alteration ratio was independent from one other and multiplicative for VPA, CBZ, and ZNS, and that the coadministered drug inhibited the drug-metabolizing enzyme competitively for PB, was adopted. The Michaelis-Menten kinetic model was adopted for PHT. The analysis clarified that CBZ, PB, and PHT significantly lowered (Pratio of ZNS alone to 0.87, 0.85, 0.85, and 0.80, respectively. VPA, CBZ, and PHT significantly increased (Pratio of PB to 1.47, 1.18, and 1.19, respectively. The daily PHT dose was decreased to 0.89, 0.91, 0.90, and 0.84 the dose of PHT alone to maintain C(t) in the therapeutic range

  12. Interactions between hormonal contraception and antiepileptic drugs

    DEFF Research Database (Denmark)

    Reimers, Arne; Brodtkorb, Eylert; Sabers, Anne

    2015-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...... 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...

  14. 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 ...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  15. 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.

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

    NARCIS (Netherlands)

    X. Qiao

    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 w

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

    OpenAIRE

    2011-01-01

    Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.

  18. Interchangeability of generic anti-epileptic drugs: a quantitative analysis of topiramate and gabapentin.

    NARCIS (Netherlands)

    Maliepaard, M.; Banishki, N.; Gispen-de Wied, C.C.; Teerenstra, S.; Elferink, A.J.

    2011-01-01

    PURPOSE: The objective of this study was to determine whether the so-called "shift" or "drift" problem might occur when generic anti-epileptic drugs are interchanged, and thus to assess if generic anti-epileptic drugs are interchangeable and can be used in an efficacious and safe way on the basis of

  19. Psychopathology in pediatric epilepsy: Role of antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Rochelle eCaplan

    2012-12-01

    Full Text Available Children with epilepsy are usually treated with antiepileptic drugs (AEDS. Some AEDs adversely affect behavior in susceptible children. Since psychiatric comorbidity is prevalent in pediatric epilepsy, this paper attempts to disentangle these AED side effects from the psychopathology associated with this illness. It first outlines the clinical and methodological problems involved in determining if AEDs contribute to the behavior and emotional problems of children with epilepsy. It then presents research evidence for and against the role AEDs play in the psychopathology of children with epilepsy, and outlines how future studies might investigate this problem. A brief description of how to clinically separate out AED effects from the complex illness-related and psychosocial factors that contribute to the behavior difficulties of children with epilepsy concludes the paper.

  20. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    Science.gov (United States)

    Nie, Qingmei; Su, Baohua; Wei, Jianping

    2016-01-01

    Epilepsy is one of the few neurologic disorders that requires a constant treatment during pregnancy. Epilepsy affects 0.3–0.8% of pregnant women. Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy requires monitoring and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. AEDs are also commonly used for psychiatric disorders, pain disorders, and migraines. The types of malformations that can result in fetuses exposed to AEDs include minor anomalies, major congenital malformations, intrauterine growth retardation, cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present review, we analyzed and summarized the current understanding of neurological development in fetuses that are exposed to various AEDs administered to pregnant epileptic women. PMID:27698740

  1. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    Science.gov (United States)

    Nie, Qingmei; Su, Baohua; Wei, Jianping

    2016-01-01

    Epilepsy is one of the few neurologic disorders that requires a constant treatment during pregnancy. Epilepsy affects 0.3–0.8% of pregnant women. Prescription of antiepileptic drugs (AEDs) to pregnant women with epilepsy requires monitoring and maintaining a balance between limiting seizures and decreasing fetal exposure to the potential teratogenic effects. AEDs are also commonly used for psychiatric disorders, pain disorders, and migraines. The types of malformations that can result in fetuses exposed to AEDs include minor anomalies, major congenital malformations, intrauterine growth retardation, cognitive dysfunction, low IQ, microcephaly, and infant mortality. In the present review, we analyzed and summarized the current understanding of neurological development in fetuses that are exposed to various AEDs administered to pregnant epileptic women.

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

    OpenAIRE

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

    2015-01-01

    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 Ma...

  3. Evidence for epistatic interactions in antiepileptic drug resistance.

    Science.gov (United States)

    Kim, Myeong-Kyu; Moore, Jason H; Kim, Jong-Ki; Cho, Ki-Hyun; Cho, Yong-Won; Kim, Yo-Sik; Lee, Min-Cheol; Kim, Young-Ok; Shin, Min-Ho

    2011-01-01

    To investigate the epistatic interactions involved in antiepileptic drug (AED) resistance, 26 coding single-nucleotide polymorphisms (SNPs) were selected from 16 candidate genes. A total of 200 patients with drug-resistant localization-related epilepsy and 200 patients with drug-responsive localization-related epilepsy were genotyped individually for the SNPs. Rather than using the traditional parametric statistical method, a new statistical method, multifactor dimensionality reduction (MDR), was used to determine whether gene-gene interactions increase the risk of AED resistance. The MDR method indicated that a combination of four SNPs (rs12658835 and rs35166395 from GABRA1, rs2228622 from EAAT3 and rs2304725 from GAT3) was the best model for predicting susceptibility to AED resistance with a statistically significant testing accuracy of 0.625 (P < 0.001) and cross-validation consistency of 10/10. This best model had an odds ratio of 3.68 with a significant 95% confidence interval of 2.32-5.85 (P < 0.0001). Our results may provide meaningful information on the mechanism underlying AED resistance and, to the best of our knowledge, this is the first report of evidence for gene-gene interactions underlying AED resistance. PMID:21124337

  4. Antiepileptic Drugs with Mood Stabilizing Properties and Their Relation with Psychotropic Drug Use in Institutionalized Epilepsy Patients with Intellectual Disability

    Science.gov (United States)

    Leunissen, C. L. F.; de la Parra, N. M.; Tan, I. Y.; Rentmeester, Th. W.; Vader, C. I.; Veendrick-Meekes, M. J. B. M.; Aldenkamp, A. P.

    2011-01-01

    A large number of patients with epilepsy and intellectual disability take medication, amongst which antiepileptic and psychotropic drugs, often simultaneously. Certain antiepileptic drugs have mood-stabilizing properties, e.g. carbamazepine, valproic acid and lamotrigine. The aim of this study was to investigate whether the use of these…

  5. Polycystic ovary syndrome in patients on antiepileptic drugs

    Science.gov (United States)

    Viswanathan, Lakshminarayanapuram G.; Satishchandra, Parthasarathy; Bhimani, Bipin C.; Reddy, Janardhan YC; Rama Murthy, Batchu S.; Subbakrishna, Doddaballapura K.; Sinha, Sanjib

    2016-01-01

    Objective: This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA. Materials and Methods: This prospective study included 190 women aged 18–45 years, who had epilepsy or BPAD (on VPA), and consented for study. Patients were grouped as Group 1 (n = 40): WWE on VPA, Group 2 (n = 50): WWE on CBZ, Group 3 (n = 50): WWE on PB, Group 4 (n = 30): drug naïve WWE, and Group 5 (n = 20): women with BPAD on VPA. All women were interviewed for medical, menstrual, drug and treatment history, nature of epilepsy, and seizure control. Chi-square test and Fisher's exact test were done to compare results between the groups. Results: Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11). Conclusions: The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted. PMID:27570385

  6. 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.

  7. Influence of normal versus slow antiepileptic drugs withdrawal on seizure recurrence in patients with epilepsy

    Institute of Scientific and Technical Information of China (English)

    王凌玲

    2013-01-01

    Objective To explore the influence of normal and slow antiepileptic drugs(AEDs) withdrawal on recurrence of epilepsy. Methods Epileptic patients with seizure-free more than 2 years were recruited to the study. They were first divided into normal

  8. 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)?

  9. 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.

  10. 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

  11. Enhancing antiepileptic drug adherence: a randomized controlled trial.

    Science.gov (United States)

    Brown, Ian; Sheeran, Paschal; Reuber, Markus

    2009-12-01

    Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (Pintention intervention may be an easy-to-administer and effective means of promoting AED adherence. PMID:19864187

  12. Analysis of nocebo effects of antiepileptic drugs across different conditions.

    Science.gov (United States)

    Zaccara, Gaetano; Giovannelli, Fabio; Giorgi, Filippo Sean; Franco, Valentina; Gasparini, Sara

    2016-07-01

    The aim of this study was to assess the nocebo effect in all randomised controlled trials (RCTs) exploring the effect of antiepileptic drugs (AEDs) in the clinical conditions in which these compounds have been studied with the exception of epilepsy. We searched for all double-blind, placebo-controlled trials performed in adult patients, testing AEDs in any clinical condition except epilepsy. The following data were extracted from the placebo arms: the number of randomized patients, the number of patients withdrawing because of adverse effects (AEs), and the number of patients with 11 predefined AEs (dizziness, ataxia/coordination abnormal, diplopia, somnolence, fatigue, headache, memory impairment, tremor, abnormal thinking, anxiety and depression). Outcome measures were the percentages of patients whithdrawing due to AEs and reporting the selected AEs. RCTs included in the analysis were grouped in six main categories of clinical conditions (pain, movement disorders, psychiatric disorders, substance abuse, obesity and binge eating disorders, and miscellanea). Proportions of patients with 95 % confidence intervals (CIs) have been calculated for all reported outcome measures. Thirteen AEDs were studied and the total number of selected RCTs was 157. Significant percentages of placebo-treated patients withdrawing due to AEs and with specific AEs were observed in several cases. Significant differences emerged across different conditions. Comparisons with results of a previous meta-analysis on all RCTs in patients with drug-resistant epilepsies showed that ataxia, diplopia and fatigue were significantly more frequent, and patients withdrawing were significantly less frequent, in placebo-treated epileptic patients. Significant differences have been identified in the AEDs-induced nocebo effect across different conditions. Placebo-treated epilepsy patients have significantly more frequent neurological AEs. PMID:26810717

  13. Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

    OpenAIRE

    Kartik N. Shah; Rana, Devang A.; Patel, Varsha J.

    2014-01-01

    Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetra...

  14. Current Status of the New Antiepileptic Drugs in Chronic Pain

    Science.gov (United States)

    Sidhu, Harpreet S.; Sadhotra, Akshay

    2016-01-01

    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 should be

  15. 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 and...

  16. 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

  17. 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 ...

  18. 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.

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

    Science.gov (United States)

    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

    2014-01-01

    Objective To determine whether use of antiepileptic drugs during pregnancy may increase the risk of spontaneous abortion or stillbirth. Design Population based cohort study. Setting Register based study in Denmark, 1997-2008. Participants 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. Main outcome measures 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. Results 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). Conclusion Among women with epilepsy and when analysing the risk in antiepileptic drug discordant pregnancies

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  1. 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

  2. Four-year outcome after early withdrawal of antiepileptic drugs in childhood epilepsy

    NARCIS (Netherlands)

    Geerts, AT; Niermeijer, JMF; Arts, WFM; Brouwer, OF; Stroink, H; Peeters, EAJ; van Donselaar, CA

    2005-01-01

    Four-year follow-up of children with epilepsy included in a randomized trial of early withdrawal of antiepileptic drugs showed that 51% achieved a terminal remission of at least 2 years without medication and 21% with medication; 15% had seizures during the fourth year. Early medication withdrawal i

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

    DEFF Research Database (Denmark)

    Tsiropoulos, Ioannis; Andersen, Morten; Nymark, Tine;

    2008-01-01

    PURPOSE: To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture. METHODS: We performed a case-control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals ...

  4. Anti-epileptic drug changes and quality of life in the community

    NARCIS (Netherlands)

    Wassenaar, M.; Leijten, F.S.S.; Sander, J.W.; Uijl, S.G.; Egberts, A.C.G.

    2016-01-01

    Objective: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change

  5. [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.

  6. New Developments in Antiepileptic Drug Resistance: An Integrative View

    OpenAIRE

    Schmidt, Dieter; Löscher, Wolfgang

    2009-01-01

    Current theories on drug resistance in epilepsy include the drug transporter hypothesis, the drug target hypothesis, and a novel approach called the inherent severity model of epilepsy, which posits that the severity of the disease determines its relative response to medication. Valuable as each of these hypotheses is, none is currently a stand-alone theory that is able to convincingly explain drug resistance in human epilepsy. As a consequence, it may be of interest to update and integrate t...

  7. Mexiletine and its Interactions with Classical Antiepileptic Drugs: An Isobolographic Analysis.

    Science.gov (United States)

    Borowicz-Reutt, Kinga K; Banach, Monika; Piskorska, Barbara

    2016-05-01

    Using the mouse maximal electroshock test, the reference model of tonic-clonic seizures, the aim of the present study was to determine the type of interaction between mexiletine (a class IB antiarrhythmic drug) and classical antiepileptics: valproate, carbamazepine, phenytoin, and phenobarbital. Isobolographic analysis of obtained data indicated antagonistic interactions between mexiletine and valproate (for fixed ratio combinations of 1:1 and 3:1). Additivity was observed between mexiletine and valproate applied in proportion of 1:3 as well as between mexiletine and remaining antiepileptics for the fixed ratios of 1:3, 1:1, and 3:1. Neither motor performance nor long-term memory were impaired by mexiletine or antiepileptic drugs regardless of whether they were administered singly or in combination. Mexiletine did not significantly affected brain concentrations of carbamazepine, phenobarbital or phenytoin. In contrast, the antiarrhythmic drug decreased by 23 % the brain level of valproate. This could be, at least partially, the reason of antagonistic interaction between the two drugs. In conclusion, the observed additivity suggests that mexiletine can be safely applied in epileptic patients treated with carbamazepine, phenytoin or phenobarbital. Because of undesirable pharmacodynamics and pharmacokinetic interactions with valproate, mexiletine should not be used in such combinations. PMID:26738990

  8. Antiepileptic drug use in a nursing home setting: a retrospective study in older adults

    Science.gov (United States)

    Callegari, Camilla; Ielmini, Marta; Bianchi, Lucia; Lucano, Melissa; Bertù, Lorenza; Vender, Simone

    2016-01-01

    Summary The authors set out to examine qualitatively the use of antiepileptic drugs (AEDs) in a population of older adults in a nursing home setting, evaluating aspects such as specialist prescriptions and changes in dosage. This retrospective prevalence study was carried out in a state-funded nursing home that provides care and rehabilitation for elderly people. The first objective of the study was to determine the prevalence of AED use in this population. The second objective was to monitor AED dosage modifications during the fifteen-month study period, focusing on the safety and the tolerability of AEDs. In the period of time considered, 129 of 402 monitored patients received at least one anti-epileptic therapy. The prevalence of AED use was therefore 32%. Gabapentin was found to be the most commonly prescribed drug, with a frequency of 29%, and it was used mainly for anxiety disorders, psychosis, neuropathic pain and mood disorders. PMID:27358221

  9. Effects of Neonatal Antiepileptic Drug Exposure on Cognitive, Emotional, and Motor Function in Adult Rats

    OpenAIRE

    Patrick A Forcelli; Kozlowski, Ryan; Snyder, Charles; Kondratyev, Alexei; Gale, Karen

    2012-01-01

    Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13...

  10. Effects of chronic treatment with commonly used antiepileptic drugs on passive avoidance learning in prepubertal rats

    OpenAIRE

    Yildirim, Mehmet; ABİDİN, Ismail; CANSU, Ali

    2013-01-01

    Antiepileptic drugs (AEDs), which are widely used to control and prevent epileptic seizures in children with epilepsy, have potential cognitive side effects. There have been several reports respecting different effects of the first and second generation ADEs on learning and memory. Therefore, we investigated the effects of valproate, carbamazepine, levetiracetam, oxcarbazepine, lamotrigine and topiramate, administered chronically by gavage for 21 days, on learning and memory retention of male...

  11. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

    OpenAIRE

    Morte, Maria I.; Carreira, Bruno P.; Falcão, Maria J.; Ambrosio, António M.; Soares-da-Silva, Patrício; Araújo, Inês M.; Carvalho, Caetana M.

    2013-01-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic p...

  12. Fluorination of an antiepileptic drug: A self supporting transporter by oxygen enrichment mechanism.

    Science.gov (United States)

    Natchimuthu, V; Amoros, J; Ravi, S

    2016-03-01

    Drug therapy of seizures involves producing high levels of antiepileptic drugs in the blood. Drug must enter the brain by crossing from the blood into the brain tissue, called a transvascular route (TVR). Even before the drug can reach the brain tissue, factors such as systemic toxicity, macrophage phagocytises and reduction in oxygen content limit the success of this TVR. Encapsulating the drug within a nano scale delivering system, synthesising drugs with low molecular weight are the best mechanisms to deliver the drug to the brain. But through this article, we have explored a possibility of attaching a molecule 4-(trifluoromethyl) benzoic acid (TFMBA), that possess more number of fluorine atom, to benzodiazepine (BDZ) resulting in an ionic salt (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine5,11(10H,11aH)-dione with 4-(trifluoromethyl)benzoic acid. By this way, reducing the toxicity of BDZ than the conventional anti-epileptic drugs (AEDs), increasing the solubility, reducing the melting point, enriching the TVR with excess oxygen content with the support of fluorine. With all these important prerequisites fulfilled, the drug along with the attached molecule is expected to travel more comfortably through the TVR without any external support than any other conventional AEDs. FTIR, (1)H NMR, (13)C NMR, HRMS spectroscopy, HRTEM and In vitro cytotoxicity analysis supports this study. PMID:26708322

  13. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  14. 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

  15. Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug.

    Science.gov (United States)

    Doeser, Anna; Dickhof, Gesa; Reitze, Margit; Uebachs, Mischa; Schaub, Christina; Pires, Nuno Miguel; Bonifácio, Maria João; Soares-da-Silva, Patrício; Beck, Heinz

    2015-02-01

    In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting a substantial fraction of patients. Many of the currently available antiepileptic drugs target voltage-gated sodium channels, leading to a rate-dependent suppression of neuronal discharge. A loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels. There is a need both for compounds that overcome this resistance mechanism and for novel drugs that inhibit the process of epileptogenesis. We show that eslicarbazepine acetate, a once-daily antiepileptic drug, may constitute a candidate compound that addresses both issues. Eslicarbazepine acetate is converted extensively to eslicarbazepine after oral administration. We have first tested using patch-clamp recording in human and rat hippocampal slices if eslicarbazepine, the major active metabolite of eslicarbazepine acetate, shows maintained activity in chronically epileptic tissue. We show that eslicarbazepine exhibits maintained use-dependent blocking effects both in human and experimental epilepsy with significant add-on effects to carbamazepine in human epilepsy. Second, we show that eslicarbazepine acetate also inhibits Cav3.2 T-type Ca(2+) channels, which have been shown to be key mediators of epileptogenesis. We then examined if transitory administration of eslicarbazepine acetate (once daily for 6 weeks, 150 mg/kg or 300 mg/kg) after induction of epilepsy in mice has an effect on the development of chronic seizures and neuropathological correlates of chronic epilepsy. We found that eslicarbazepine acetate exhibits strong antiepileptogenic effects in experimental epilepsy. EEG monitoring showed that transitory eslicarbazepine acetate treatment resulted in a significant decrease in seizure activity at the chronic state, 8 weeks after the end of treatment. Moreover, eslicarbazepine acetate treatment resulted in a

  16. Antiepileptic drugs and vitamin B6 plasma levels in adult patients

    OpenAIRE

    Linnebank, M.; Moskau, S; Semmler, A; Widman, G; Weller, M.; Kallweit, U; Elger, C E

    2012-01-01

    Treatment with several antiepileptic drugs (AED) is associated with lower serum concentrations of folate or vitamin B12. This prospective monocenter study analyzed vitamin B6 blood levels in 400 serial patients with epilepsy, AED-treated (n=385), untreated (n=15) and healthy controls (n=233). The mean plasma vitamin B6 levels of the AED-treated (12.1±10.1; p=0.093) and the untreated patients (15.6±12.4; p=0.664) were not significantly different from the controls (13.9±15.2). These observation...

  17. 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.

  18. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications.

    Science.gov (United States)

    Tomson, Torbjörn; Landmark, Cecilie Johannessen; Battino, Dina

    2013-03-01

    Pregnancy is a state where pharmacokinetic changes are more pronounced and more rapid than during any other period of life. The consequences of such changes can be far reaching, not least in the management of epilepsy where the risks with uncontrolled seizures during pregnancy need to be balanced against potential teratogenic effects of antiepileptic drugs (AEDs). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AEDs and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AEDs at any level from absorption, distribution, metabolism, to elimination. The effect varies depending on the type of AED. The most pronounced decline in serum concentrations is seen for AEDs that are eliminated by glucuronidation (UGT), in particular lamotrigine where the effect may be profound. Serum concentrations of AEDs that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AEDs, such as carbamazepine seem to be affected only marginally by pregnancy. Data on pharmacokinetics during pregnancy are lacking completely for some of the newer generation AEDs: pregabalin, lacosamide, retigabine, and eslicarbazepine acetate. Where data are available, the effects of pregnancy on serum concentrations seem to vary considerably individually and are thus difficult to predict. Although large-scale systematic studies of the clinical relevance of the pharmacokinetic alterations are lacking, prospective and retrospective case series have reported an association between declining serum concentrations and deterioration in seizures control. The usefulness of routine monitoring of AED serum concentrations in pregnancy and of dose adjustments based on falling levels, are discussed in this review. We suggest that monitoring could be important, in particular when women have been titrated to the lowest effective AED

  19. Transient splenial lesion of the corpus callosum associated with antiepileptic drugs: evaluation by diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Masayuki; Takeda, Kan [Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Shiroyama, Takashi [Department of Psychiatry, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Tsukahara, Hirokazu [Department of Pediatrics, Fukui Medical University, Fukui (Japan); Shimono, Taro [Department of Radiology, Kinki University School of Medicine, Osaka (Japan); Aoki, Shigeki [Department of Radiology, Tokyo University School of Medicine, Tokyo (Japan)

    2003-08-01

    Transient focal lesions in the splenium of the corpus callosum have been reported in epileptic patients receiving antiepileptic drugs. The characteristic imaging features included an oval high signal lesion on T2-weighted images in the central part of the splenium, no enhancement on post-contrast MR images, and complete reversibility without specific treatment. We report identical MR imaging findings in a depressive patient who had received antiepileptic drugs. In addition, diffusion-weighted MR imaging findings are described in our case, which is the first report on this unique lesion associated with antiepileptic drugs. Although this lesion has been assumed to be vasogenic edema in the previous reports, diffusion-weighted MR imaging showed markedly restricted diffusion of the lesion in the present case, suggesting that cytotoxic edema was the main pathophysiological abnormality. (orig.)

  20. Transient splenial lesion of the corpus callosum associated with antiepileptic drugs: evaluation by diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Transient focal lesions in the splenium of the corpus callosum have been reported in epileptic patients receiving antiepileptic drugs. The characteristic imaging features included an oval high signal lesion on T2-weighted images in the central part of the splenium, no enhancement on post-contrast MR images, and complete reversibility without specific treatment. We report identical MR imaging findings in a depressive patient who had received antiepileptic drugs. In addition, diffusion-weighted MR imaging findings are described in our case, which is the first report on this unique lesion associated with antiepileptic drugs. Although this lesion has been assumed to be vasogenic edema in the previous reports, diffusion-weighted MR imaging showed markedly restricted diffusion of the lesion in the present case, suggesting that cytotoxic edema was the main pathophysiological abnormality. (orig.)

  1. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  2. Antiepileptic drugs patterns in elderly inpatients in a Brazilian tertiary center, Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Telma Rocha de Assis

    2014-11-01

    Full Text Available Epilepsy is very prevalent among elderly inpatients and treatment is far from ideal. Objective To analyze prescribing patterns of antiepileptic drugs (AEDs for hospitalized elderly with epilepsy, their relations with comorbidities and comedications. Method We assessed prescription regimen of elderly patients that were under AED use for treatment of epileptic seizures, during hospitalization. One hundred and nine patients were enrolled. AED regimen was categorized into two groups: Group 1 defined as appropriate (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazan and lamotrigine and Group 2 as inappropriate (phenytoin and phenobarbital. Results We found 73.4% of patients used inappropriate AEDs (p<0.001. Monotherapy was prescribed for 71.6% of patients. The most common comorbidity was hypertension. Potentially proconvulsant drugs as comedications were used for nearly half of patients. Conclusion Inappropriate AED therapy was commonly prescribed regimen for elderly inpatients. Some recommendations are discussed for a better care of elderly inpatients with epilepsy.

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

    Directory of Open Access Journals (Sweden)

    Sander Josemir W

    2007-03-01

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

  4. 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.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  6. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

    NARCIS (Netherlands)

    Handoko, K.B.; Puijenbroek, E.P. van; Bijl, A.H.; Hermens, W.A.; Rijkom, JE Zwart-van; Hekster, Y.A.; Egberts, T.C.G.

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can ex

  7. Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs : the role of the aromatic ring

    NARCIS (Netherlands)

    Handoko, Kim B; van Puijenbroek, Eugène P; Bijl, Annemarie H; Hermens, Walter A J J; Zwart-van Rijkom, Jeannette E F; Hekster, Yechiel A; Egberts, Toine C G

    2008-01-01

    OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can ex

  8. 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...

  9. 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.

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

    International Nuclear Information System (INIS)

    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

  11. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    Science.gov (United States)

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  12. 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...

  13. Failure of antiepileptic drugs in controlling seizures in epilepsy: What do we do next?

    Directory of Open Access Journals (Sweden)

    Brahyan Galindo-Mendez

    2015-01-01

    Full Text Available Medically intractable epilepsy is a clinical condition of concern that arises when a patient with epilepsy suffers seizures, despite a trial of two or more antiepileptic drugs (AEDs suitable for the type of epilepsy that are prescribed at maximum tolerated doses, does not achieve control of seizures. This diagnosis could be related to cortical dysplasias. We report the case of a 5-year-old girl with a previous normal neurological development and no family history of epilepsy who presented with focal-type seizures at age 4. She started treatment by taking different AEDs for seizure control. She continued having frequent seizures that sometimes progressed to generalized seizures and status epilepticus. After a focal cortical resection performed in the area where interictal spikes were detected, the pathology confirmed a type IIb cortical dysplasia as the cause of the epilepsy. This article discusses cortical dysplasias as a cause of pharmacoresistant epilepsy and its treatment.

  14. The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

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    Bromley, R

    2016-09-01

    A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research. PMID:27312074

  15. Cognitive effects of antiepileptic drugs Efectos cognitivos de los medicamentos antiepilépticos

    Directory of Open Access Journals (Sweden)

    Jaime Carrizosa Moog

    2009-11-01

    Full Text Available

    Antiepileptic drugs have psychotropic and cognitive effects, either positive or negative, in some patients. The impact of these effects may be very important in epileptic subjects, especially during childhood and in the elderly. The diversity of methodological designs, of population samples, of doses and therapeutic levels makes it difficult to interpret these effects. In this article the effects of antiepileptic drugs, both traditional and novel, are reviewed on the basis of different studies in both animals and human beings.

    Los medicamentos antiepilépticos tienen efectos cognitivos y psicotrópicos, que en determinados pacientes pueden influir en el desempeño positivo o negativo. El impacto de estos efectos es muy importante en la población con epilepsia, fundamentalmente en edades de cuidado como la infancia y la ancianidad. La diversidad de diseños metodológicos, de muestras poblacionales, de dosificaciones y niveles terapéuticos hace que sea difícil la interpretación de estos efectos. Se revisan los efectos de los fármacos antiepilépticos corrientes y de los nuevos en diferentes estudios en animales y en seres humanos.

  16. Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel.

    Science.gov (United States)

    Boiteux, Céline; Vorobyov, Igor; French, Robert J; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W

    2014-09-01

    Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water-protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

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

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    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.

  18. Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions

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    Parvaneh KARIMZADEH

    2013-08-01

    Full Text Available How to Cite This Article: Karimzadeh P, Bakrani V. Antiepileptic Drug-Related Adverse Reactions And Factors Influencing These Reactions. Iran J Child Neurol. 2013 Summer; 7(3:23-27. ObjectiveAccording to the basic role of drug side effects in selection ofan appropriate drug, patient compliance and the quality of life inepileptic patients, and forasmuch as new dugs with unknown side effect have been produced and introduced, necessity of this research and similar studies is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED related adverse reactions in children treated with AEDs.Material & MethodsIn this descriptive study, children less than 14 years old with AEDside effects referred to the Children’s Medical Center and MofidChilderen’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 (Food, bite, non-AEDs, etc..ResultsA total of 70 patients with AED reaction were enrolled in thisstudy. 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 incidence of systemic and laboratory adverse events was less than similar studies. The most common culprit was phenobarbital (70% and the least common was lamotrigine (1.4%.ConclusionIn 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. Refrences1. Blume WT, Lu¨ders HO, Mizrahi E, et al. Glossary of descriptive terminology for

  19. Practical Use of Newer Antiepileptic Drugs as Adjunctive Therapy in Focal Epilepsy.

    Science.gov (United States)

    Brodie, Martin J

    2015-11-01

    This article lays the background for, and discusses the practical issues surrounding, the adjunctive use of the last four antiepileptic drugs (AEDs) to be licensed for the treatment of pharmacoresistant focal seizures in the UK and elsewhere. More than 30% of adolescent and adult patients will not be fully controlled on the currently available therapeutic armamentarium. After not responding to their first three AED schedules, only a handful of patients attained seizure freedom on subsequent regimens. To optimise the response to any new AED in this setting, it is often necessary to reduce the existing drug burden. The pharmacology, tolerability and safety, and everyday use of lacosamide, eslicarbazepine acetate, retigabine (ezogabine) and perampanel will be reviewed and discussed. This will be accompanied by data from prospective audits with each drug undertaken at the Western Infirmary in Glasgow, Scotland, and a report of their successful introduction in an illustrative case. Overall, there is a large variation in the course of refractory epilepsy and the effect of AED therapy on this process seems minimal. Nevertheless, a number of patients will benefit from the introduction of each new AED, with some becoming seizure-free. PMID:26507832

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

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    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

  1. P-glycoprotein alters blood–brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy

    Directory of Open Access Journals (Sweden)

    Ma A

    2013-12-01

    Full Text Available Aimei Ma,1,* Cuicui Wang,2,3,* Yinghui Chen,2,3 Weien Yuan4 1Department of Neurology, The People's Hospital of Shanxi Province, Taiyuan, 2Department of Neurology, Jinshan Hospital, Fudan University, 3Department of Neurology, Shanghai Medical College, Shanghai, 4School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood–brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy. Keywords: P-glycoprotein, medically intractable epilepsy, antiepileptic drugs, amygdala kindling, verapamil

  2. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons.

    Science.gov (United States)

    Morte, Maria I; Carreira, Bruno P; Falcão, Maria J; Ambrósio, António F; Soares-da-Silva, Patrício; Araújo, Inês M; Carvalho, Caetana M

    2013-12-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellular-regulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3mM, for 24h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK. These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent. PMID:24055897

  3. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age: an update.

    Science.gov (United States)

    Italiano, Domenico; Perucca, Emilio

    2013-08-01

    Epilepsies occur across the entire age range, and their incidence peaks in the first years of life and in the elderly. Therefore, antiepileptic drugs (AEDs) are commonly used at the extremes of age. Rational prescribing in these age groups requires not only an understanding of the drugs' pharmacodynamic properties, but also careful consideration of potential age-related changes in their pharmacokinetic profile. The present article, which updates a review published in 2006 in this journal, focuses on recent findings on the pharmacokinetics of new-generation AEDs in neonates, infants, children, and the elderly. Significant new information on the pharmacokinetics of new AEDs in the perinatal period has been acquired, particularly for lamotrigine and levetiracetam. As a result of slow maturation of the enzymes involved in glucuronide conjugation, lamotrigine elimination occurs at a particularly slow rate in neonates, and becomes gradually more efficient during the first months of life. In the case of levetiracetam, elimination occurs primarily by renal excretion and is also slow at birth, but drug clearance increases rapidly thereafter and can even double within 1 week. In general, infants older than 2-3 months and children show higher drug clearance (normalized for body weight) than adults. This pattern was confirmed in recent studies that investigated the pediatric pharmacokinetics of several new AEDs, including levetiracetam, rufinamide, stiripentol, and eslicarbazepine acetate. At the other extreme of age, in the elderly, drug clearance is generally reduced compared with younger adults because of less efficient drug-metabolizing activity, decreased renal function, or both. This general pattern, described previously for several AEDs, was confirmed in recent studies on the effect of old age on the clearance of felbamate, levetiracetam, pregabalin, lacosamide, and retigabine. For those drugs which are predominantly eliminated by renal excretion, aging

  4. Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

    Institute of Scientific and Technical Information of China (English)

    Fei Xu; Qionghua Feng; Liang Yu; Jie Liu; Hongbin Sun

    2007-01-01

    BACKGROUND: Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words,dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc.OBJECTIVE: To compare the effects of topiramate with traditional anti-epileptic drugs (including carbamazepine and Valproic acid (VPA) on cognitive function of patients with epilepsy.DESIGN: Observational experiment, self-control and intergroup comparison.SETTING: Sichuan Academy of Medical Science.PARTICIPANTS: Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People's Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram (EEG). The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit: traditional antiepileptic drugs group (AEDs group, n =44) and topiramate (TPM) group (n =43).partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures.The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 months after administration by using Wechsler Adult Intelligence Scale(WAIS) or Wechsler Intelligence Scale for Children (WISC, Chinese edition), (Higher scores indicated better cognitive function), Stroop color word interference, test of memory

  5. [Exalief as a newer antiepileptic drug for adjunctive therapy of refractory partial-onset seizures].

    Science.gov (United States)

    Ermolenko, N A; Buchneva, I A

    2014-01-01

    Results of a multicenter international study on the efficacy of exalief (eslicarbazepine acetate (ESL)), a newer blocker of voltage-gated sodium channels and T-type voltage gated calcium channels, for adjunctive therapy of refractory partial-onset seizures are presented. A clinical program included phase II (BIA-2093-201) followed by three phase Ill studies (BIA-2093-301, -302 and-303), each of which was accompanied by an additional open one-year study (301 E, 302E, 303E). In three parallel phase Ill studies patients were randomized to receive ESL in single doses 400, 800, 1200 mg or placebo together with 1 - 3 antiepileptic drugs used in stable doses, with the exception of felbamate and oxcarbazepine. The design of the study included 8-week initial period, double-blind phase (2-week titration period, 12-week maintenance period), 4-week dose reduction period. The results of clinical phase II trials demonstrated the high efficacy and best tolerability profile for single dose titration regimen. Median changes in the frequency of partial-onset seizures were greater (p<0,0001) in patients receiving 800 and 1200 mg ESL (35 and 39%)compared to placebo (15%). The proportion of treatment responders was significantly higher in the groups treated with ESL indoses 800 mg (36%) and 1200 mg (44%) compared to the placebo group (22%). The aversive effects of the drug were of mild or moderate severity. Treatment retention was higher in patients receiving ESL (84,9% of patients completed the 6-month treatment period and 76,6% completed the one-year period). The use of ESL leads to the reduction in partial seizure frequency and the increase in the proportion of treatment responders. The drug has a good tolerability profile. PMID:25629136

  6. 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.

  7. Recent and future antiepileptic drugs and their impact on cognition: what can we expect?

    Science.gov (United States)

    Mula, Marco

    2012-06-01

    Cognitive problems are frequently observed in patients with epilepsy and the relative contribution of antiepileptic drugs (AEDs) in this respect is determinant. During the past few years, a number of new AEDs have been introduced, and new compounds will be probably available in the forthcoming years. The ideal AED would be the one characterized by good efficacy with no negative effects on cognitive functions, mood and behavior. This paper is aimed at discussing the potential impact on cognition of a number of new compounds, namely lacosamide, rufinamide, retigabine, eslicarbazepine acetate, brivaracetam, perampanel and ganaxolone. In almost all cases, specific data on cognitive functions are not yet available, and it is possible only to speculate on their potential impact considering the mechanism of action and the adverse event profile in placebo-controlled studies. Lacosamide, eslicarbazepine acetate and probably brivaracetam are promising and will probably exhibit very limited impact on cognition. Conversely, retigabine may be more problematic, needing low starting doses and slow titration rates to improve cognitive tolerability. Data on rufinamide are restricted to special populations such as Lennox-Gastaut syndrome. Perampanel and ganaxolone are still in Phase III development, but the mechanism of action of these compounds is in line with a more sedative than neutral profile. PMID:22650169

  8. Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X).

    Science.gov (United States)

    Bialer, Meir; Johannessen, Svein I; Levy, René H; Perucca, Emilio; Tomson, Torbjörn; White, H Steve

    2010-12-01

    The Tenth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT X, took place in Eilat, Israel from the 25th to 29th of April 2010. About 200 basic scientists, clinical pharmacologists and neurologists from 25 countries attended the conference, whose main themes included learning from the past: Lessons learnt after 18 years of Eilat Conferences and Detecting assessing and preventing adverse effects of AEDs. Consistent with previous formats of this conference, a large part of the program was devoted to a review of AEDs in development, as well as updates on AEDs introduced since 1994. Like the previous EILAT (EILAT IX) manuscript, the current (EILAT X) manuscript focuses only on the preclinical and clinical pharmacology of AEDs that are currently in development. These include brivaracetam, carisbamate, 2-deoxy-glucose, ganaxolone, huperizine A, ICA-105665, NAX-5055, retigabine, perampanel, T-2007, valnoctamide and YK3089. Since the previous Eilat Conference (EILAT IX-2008) two new AEDs; eslicarbazepine acetate and lacosamide have been marketed and three new AEDs in development not included in the EILAT IX manuscript were added: ICA-105665, perampanel and valnoctamide. The CNS efficacy of these compounds in anticonvulsant animal models as well as other disease model systems are presented in Tables 1 and 2 and their proposed mechanism of action at summarized in Table 3. PMID:20970964

  9. 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. PMID:26475992

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    D. V. Dmitrenko

    2014-01-01

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

  12. 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)....

  13. Role of P-glycoprotein in refractoriness of seizures to antiepileptic drugs in Lennox-Gastaut syndrome.

    Science.gov (United States)

    Kumar, Achal; Tripathi, Deepak; Paliwal, Vimal Kumar; Neyaz, Zafar; Agarwal, Vikas

    2015-02-01

    Mechanism of seizure refractoriness to antiepileptic drugs in children with Lennox-Gastaut syndrome is not known. Efflux of antiepileptic drugs due to increased expression/function of P-glycoprotein, a multidrug efflux transporter protein on the cell surface is a proposed mechanism. The authors studied the expression/function of P-glycoprotein on peripheral blood mononuclear cells of 29 children with Lennox-Gastaut syndrome, 23 children with other epilepsies, and 19 healthy children. The authors found a higher P-glycoprotein expression/function in Lennox-Gastaut syndrome, a higher percent positive cells as compared to children with other epilepsy (P P = 0.012), higher P-glycoprotein expression as compared to healthy controls (P = 0.003), a higher total P-glycoprotein expression (relative florescence intensity × percent positive cells) as compared to children with other epilepsies (P P P-glycoprotein function as compared to children with other epilepsies (P = 0.001) and healthy controls (P = 0.002). These findings may explain seizure refractoriness to anti-epileptic drugs in Lennox-Gastaut syndome.

  14. Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

    Directory of Open Access Journals (Sweden)

    Kartik N. Shah

    2014-10-01

    Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures. [Int J Basic Clin Pharmacol 2014; 3(5.000: 830-835

  15. Influence of coadministered antiepileptic drugs on serum phenobarbital concentrations in epileptic patients: quantitative analysis based on a suitable transforming factor.

    Science.gov (United States)

    Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Shushi

    2004-12-01

    This study investigated most suitable transforming factor related to the daily Phenobarbital dose (D) providing a steady-state serum concentration (Ct) and analyzed the influences of concomitant antiepileptic drugs on Ct quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 326 epileptic patients treated with multiple oral administrations of phenobarbital (PB) as a powder, were used for the analysis. A total of 156 patients were administered PB alone, and 92, 57, and 21 patients were coadministered one, two, and three different antiepileptic drugs, respectively. Valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam, and ethosuximide were coadministered with PB. For administration of PB alone, four types of transforming factor corresponding to clearance, i.e., total body weight, total body water volume, body surface area and extracellular water volume (VECW) were proposed. With VECW as a transforming factor, the level/dose (L/D) ratio (:Ct/(D/VECW)) was independent of the patient's age and gender. Ct was dependent on only one variable regarding D/VECW and expressed as Ct=0.989 x (D/VECW). The coadministration of one drug caused a difference in the gradient of the regression line of PB alone, and the influence of each drug was detected by dividing each mean L/D ratio of PB plus one other drug by that of PB alone. VPA, CBZ, and PHT significantly increased (pratio to 1.48, 1.35, and 1.23 of the value for PB alone, respectively. With coadministration of multiple drugs, the L/D ratio rose significantly (pratio Ri, representing the influence of each antiepileptic drug on the L/D ratio of PB alone. A model based on the assumption that each coadministered drug competitively inhibited PB-metabolizing enzyme, was adopted. The analysis clarified that VPA, CBZ, and PHT significantly increased (pratio of PB to 1.466, 1.177, and 1.186, respectively. In the case of the addition or discontinuance of concomitant

  16. Effect of antiepileptic drug therapy on thyroid hormones among adult epileptic patients: An analytical cross-sectional study

    Science.gov (United States)

    Adhimoolam, Mangaiarkkarasi; Arulmozhi, Ranjitha

    2016-01-01

    Objective: The objective of the study was to evaluate and compare the effect of conventional and newer antiepileptic drugs (AEDs) on thyroid hormone levels in adult epileptic patients. Methods: A hospital-based, analytical cross-sectional study was conducted among the adult epileptic patients receiving conventional AEDs (Group 2) or newer AEDs (Group 3) for more than 6 months. Serum thyroid hormone levels including free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were analyzed and the hormonal status was compared with healthy control subjects (Group 1). Findings: Sodium valproate and phenytoin were commonly used conventional AEDs; levetiracetam and topiramate were common among the newer drugs. There was a statistically significant decrease in serum fT4 and increase in serum TSH levels (P hormone levels (fT3, fT4, and TSH; P = 0.68, 0.37, and 0.90, respectively) was observed with newer antiepileptics-treated patients when compared to control group. One-way analysis of variance followed by post hoc Dunnett's test was performed using SPSS version 17.0 software package. Conclusion: The present study showed that conventional AEDs have significant alteration in the thyroid hormone levels than the newer antiepileptics in adult epileptic patients.

  17. Do no harm - But first we need to know more: The case of adverse drug reactions with antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Gagandeep Singh

    2011-01-01

    Full Text Available An adverse drug reaction (ADR is defined by the World Health Organization as a noxious, unintended, and undesired drug effect, when used for therapeutic purposes in humans. ADRs to anti-epileptic drugs (AEDs significantly impact the quality of life of people with epilepsy and account for a little less than half of all recorded treatment failures with AEDs. Hence prevention and early recognition of ADRs constitute an important aspect of management of epilepsy. Recent developments have improved our ability to predict and hence potentially prevent the occurrence of some of the serious ADRs to AEDs. One example is the potential prediction of the risk of severe cutaneous hypersensitivity reactions including Stevens Johnson syndrome and toxic epidermal necrolysis by testing for expression of HLA BFNx011502 allele in people of Asian origin who are prescribed carbamazepine. The association between HLA BFNx011502 expression and carbamazepine skin reactions has been documented in India but the role of HLA testing in Indian populations needs to be clarified in larger studies across different ethnic groups within the country.

  18. Low potency and limited efficacy of antiepileptic drugs in the mouse 6 Hz corneal kindling model.

    Science.gov (United States)

    Leclercq, K; Matagne, A; Kaminski, R M

    2014-05-01

    Corneal kindling is a useful alternative to electrically induced amygdala or hippocampal kindling, which requires advanced surgical and EEG techniques that may not be easily available in many laboratories. Therefore the first aim of this study was to evaluate whether repeated 6 Hz corneal stimulation in mice would lead to an increased and persistent seizure response as described for higher frequency (50/60 Hz) corneal kindling. Male NMRI mice stimulated twice daily (except weekends) for 3 s with 6 Hz electrical current at 44 mA displayed robust kindling development, i.e., a progressive increase in seizure severity. The majority of the animals (about 90%) developed a fully kindled state, defined as at least 10 consecutive stage 3-5 seizures within 5 weeks of corneal stimulation. Afterwards, the fully kindled state was maintained for at least 8 weeks with only two days of stimulations per week. Next, the protective efficacy of four mechanistically different antiepileptic drugs (AEDs; clonazepam, valproate, carbamazepine and levetiracetam) was assessed and compared between 6 Hz and 50 Hz fully kindled mice. All tested AEDs showed a relatively lower potency in the 6 Hz kindling model and a limited efficacy against partial seizures was observed with carbamazepine and levetiracetam. We can conclude that 6 Hz kindling may be more advantageous than the previously described 50/60 Hz corneal kindling models due to its robustness and persistence of the fully kindled state. Furthermore, the observed low potency and limited efficacy of AEDs in 6 Hz fully kindled mice suggest that this model could be a useful tool in the discovery of novel AEDs targeting treatment resistant epilepsy.

  19. Effects of antiepileptic drugs on the serum folate and vitamin B12 in various epileptic patients

    Science.gov (United States)

    Huang, Hong-Li; Zhou, Hao; Wang, Nuan; Yu, Chun-Yu

    2016-01-01

    Epilepsy is a common neurodegenerative disease with an increasing morbidity. Clinical treatment of epilepsy includes symptomatic treatment, etiological treatment, surgery and prevention. The aim of the present study was to determine the effects of antiepileptic drugs (AEDs) on serum folate and vitamin B12 in various epileptic patients, and to examine the correlation between these effects and secondary cerebrovascular events. A total of 68 epileptic patients, diagnosed between May 2012 and May 2014, were included in the present study. The study included 8 cases of autonomic seizures, 10 cases of absence seizures, 13 cases of complex partial seizures, 28 cases of generalized tonic-clonic seizures, and 9 cases of simple partial seizures. The patients received appropriate AED treatment according to the characteristics of epileptic seizure and the treatment guidance. The differences in the serum levels of folate and vitamin B12 in these patients, and the differences in the secondary cerebrovascular events in these patients after 1 year follow-up were analyzed. The difference in the AEDs used by various epileptic patients was statistically significant (P0.05). The difference in the incidence of cerebrovascular events in these groups at follow up was not statistically significant (P>0.05). The multifactorial logistic regression analysis revealed that the serum levels of folate and vitamin B12 were the independent risk factors for epilepsy with secondary cerebrovascular events [folate: odds ratio (OR)=0.536, P=0.039; vitamin: OR=0.382, P=0.041]. In conclusion, various AEDs may decrease the serum levels of folate and vitamin B12 and affect the secondary cerebrovascular events in various epileptic patients. Thus, regular supplementation of folate and vitamin B12 may be an option.

  20. Influence of coadministered antiepileptic drugs on serum zonisamide concentrations in epileptic patients: quantitative analysis based on suitable transforming factor.

    Science.gov (United States)

    Fukuoka, Noriyasu; Tsukamoto, Toyohisa; Uno, Junji; Kimura, Michio; Morita, Shushi

    2003-12-01

    We conducted a study to clarify the most suitable transforming factor related to the daily zonisamide dose (D) providing a steady-state serum concentration (C(t)) and analyzed the influences of the concomitant use of antiepileptic drugs on C(t) quantitatively. Data obtained by routine therapeutic drug monitoring from a total of 175 epileptic patients treated with the multiple oral administrations of zonisamide (ZNS) as a powder/tablets, were used for the analysis. Employing the extracellular water volume (V(ECW)) as a transforming factor, led the level/dose (L/D) ratio (:C(t)/(D/V(ECW))) to be independent of the patient's age and sex for the administration of ZNS alone. C(t) was revealed to be dependent on only one variable regarding D/V(ECW) and expressed as C(t)=0.604x(D/V(ECW)). Phenytoin (PHT) significantly lowered (pratio to 0.76 of the value for ZNS alone. For a more detailed analysis, we defined the parameter R(i) (i=1, 2, em leader, 6) as an alteration ratio, representing the influence of each antiepileptic drug on the L/D ratio of ZNS alone. A model based on the assumption that each R(i) value was independent from one another and multiplicative, was adopted. The analysis clarified that phenobarbital, valproic acid, carbamazepine, and PHT significantly lowered (pratio of ZNS to 0.849, 0.865, 0.846, and 0.804, respectively. In the case of the addition or discontinuance of concomitant treatment with antiepileptic drugs in the same patient, the estimated L/D ratios were calculated using the value of each R(i) and compared with the measured ones. The mean of prediction error was calculated as 22.9%. Our results appear valid and R(i) should be available for clinical use. PMID:14646181

  1. Intrapatient variation in antiepileptic drug plasma concentration after generic substitution vs stable brand-name drug regimens.

    Science.gov (United States)

    Contin, Manuela; Alberghini, Lucia; Candela, Carmina; Benini, Giulia; Riva, Roberto

    2016-05-01

    Generic substitution of antiepileptic drugs (AEDs) is still a matter of controversy and concern among clinicians and patients. We aimed to assess intrasubject variation in plasma concentrations of lamotrigine (LTG), levetiracetam (LEV) and topiramate (TPM) after generic substitution compared with a stable brand-name drug regimen in a population of patients with epilepsy. A retrospective analysis was performed on prospectively collected and stored data from our therapeutic drug monitoring (TDM) database for the years 2009-2014. The main outcome variable was the proportion of patients who, after switching from branded to generic formulations, showed a greater than ±20% change in AED plasma concentrations compared to the proportion of control patients showing a change in AED plasma concentrations of the same extent while receiving stable branded formulations over repeated TDM tests. Fifty patients on LTG, 27 on LEV and 16 on TPM showing at least one TDM test while receiving generic products fulfilled the inclusion/exclusion criteria for the analysis and were compared with 200 control patients for LTG, 120 for LEV and 80 for TPM. The proportion of patients showing an intrasubject change greater than ±20% in AED plasma concentrations was similar in the brand name vs generic group compared with the control one for LTG (22% vs 33%) and LEV (44% vs 38%), while it was higher in the control group for TPM (41% vs 6%, pTPM plasma concentrations can be observed even in patients stabilized with the same brand name product over time. This suggests that any change in plasma AED concentration and possible related clinical effects after generic substitution may be not necessarily related to the switch. Our results should be confirmed by large, prospective, blinded, randomized controlled studies in people with epilepsy. PMID:26987080

  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.

  3. 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. PMID:25967117

  4. 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

    Vigabatrin is an anti-epileptic drug substance. The oral bioavailability of vigabatrin is high (60-70%), however, little is known about the mechanism(s) mediating the intestinal absorption. The aim of the present study was to identify which solute carrier(s) are involved in the absorption...... 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...

  5. ANTI-CONVULSANT ACTIVITY OF GANAXOLONE ALONE A ND IN COMPARISON WITH STANDARD ANTI-EPILEPTIC DRUGS IN RODENT MODELS

    Directory of Open Access Journals (Sweden)

    Subhani Basha

    2012-08-01

    Full Text Available ABSTRACT: BACKGROUND: Presently, treatment of epilepsy with standa rd anti-epileptic drugs is associated with a number of shortcomings invi ting us to study newer agents that would overcome these problems or search for the dr ugs or substances, which would enhance the efficacy or reduce the dose or toxicity of these standard anti-epileptic drugs. Ganaxolone (GNX (3α-hydroxy-3β-methyl-5α-pregnan-20-one, a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive a llosteric modulator of GABA A receptors, may represent a new treatment approach for epilep sy. AIM: To evaluate the effect of Ganaxolone on maximal electroshock (MES induced and Pen tylenetetrazol (PTZ induced convulsions and also their effect in combination with co nventional antiepileptic drugs (CAEDs. MATERIAL AND METHODS: Wister strain albino rats weighing 200-250 gm were used. Effects of Ganaxolone (5 &10 mg/kg alone and in combination with standard drugs were studied in MES and PTZ induced seizure model s. Abolition of tonic hind limb extension was an index of anticonvulsant activity in MES, while for PTZ seizures; failure to observe c lonus for 5sec duration for 30min was the index. F ollowing that, percentage inhibition was calculated. STATISTICS: ANOVA followed by Newman-Keuls Multiple Compar ison Test was used for analysis of data between the groups . RESULTS : In MES seizures, significant anti- epileptic activity was observed with 10mg of Ganaxolone compared to control group but has less activity when compared to that of P henobarbitone. In PTZ induced convulsions, the anti-epileptic effect of Sodium Valproate was h igher than Ganaxolone, but both were statistically significant as compared to contr ol. In PTZ-induced seizures, augmented effect s were obtained when Ganaxolone was combined wi th sodium valproate i.e. 55%. CONCLUSIONS: The results provide a lead for potential benefit of adding Ganaxolone to Sodium Valproate in the treatment of epilepsy

  6. [Plasma levels of anti-epileptic drugs. Evaluation of determinations carried out in the years 1978-1979].

    Science.gov (United States)

    Zagnoni, P; Cognazzo, A; Gerbino Promis, P C; Grasso, E

    1981-11-10

    The results of 701 determinations of antiepileptic drug plasma concentrations administered to 190 patients are described. It has been possible to reduce the number of prescribed drugs to 1.55 per patient, so that only 8.1% of subjects takes three or more drugs while 53% is on monotherapy. The use of the measurement of AEDs plasma concentrations resulted very useful: a) when Phenytoin (PHT) is prescribed; b) in epileptic children; c) when the patient takes two or more drugs; d) to evaluate the compliance. A significant increase (p less than 0.01) of the level/dose ratio of Phenobarbital (PB) when PHT is in, or over, the therapeutic range was observed, while at plasma concentrations of PHT below 10 micrograms/ml it does not influence the metabolism of PB. PMID:7301176

  7. Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats

    Institute of Scientific and Technical Information of China (English)

    Ying-hui CHEN; Cui-cui WANG; Xia XIAO; Li WEI; Guoxiong XU

    2013-01-01

    Aim:To investigate whether multidrug resistance-associated protein 1 (MRP1) was responsible for drug resistence in refractory epilepsy in amygdale kindling rats.Methods:Rat amygdale kindling was used as a model of refractory epilepsy.The expression of MRP1 mRNA and protein in the brains was examined using RT-PCR and Western blot.MRP1-positive cells in the cortex and hippocampus were studied with immunohistochemical staining.The rats were intraperitoneally injected with phenytoin (50 mg/kg) or carbamazepine (20 mg/kg),and their concentrations in the cortical extracellular fluid were measured using microdialysis and HPLC.Probenecid,a MRP1 inhibitor (40 mmol/L,50 μL) was administered through an inflow tube into the cortex 30 min before injection of the antiepileptic drugs.Results:The expression of MRP1 mRNA and protein was significantly up-regulated in the cortex and hippocampus in amygdale kindling rats compared with the control group.Furthermore,the number of MRP1-positive cells in the cortex and hippocampus was also significantly increased in amygdale kindling rats.Microdialysis studies showed that the concentrations of phenytoin and carbamazepine in the cortical extracellular fluid were significantly decreased in amygdale kindling rats.Pre-administration of probenecid could restore the concentrations back to their control levels.Conclusion:Up-regulation of MRP1 is responsible for the resistance of brain cells to antiepileptic drugs in the amygdale kindling rats.

  8. 药物基因组学与抗癫(癎)药物治疗%Pharmacogenomics and antiepileptic drugs

    Institute of Scientific and Technical Information of China (English)

    吴晔

    2015-01-01

    药物基因组学是在整个基因组水平,通过探讨基因的DNA或RNA的变异与药物效应和不良反应之间的相关性,来研究基因的变异对于个体对药物反应的影响.药物基因组学研究的最终目的是实现个体化治疗.现就药物基因组学在抗癫(癎)药物治疗中的角色进行简述.%Pharmacogenomics is defined as the study of variation in DNA and RNA at the whole genome level,and its effects on drug response including effectiveness and adverse events.Pharmacogenomics is helpful for individualized drug therapy.The role of pharmacogenomics in antiepileptic drugs in therapy of epilepsy was briefly reviewed.

  9. Effect of magnesium oxide on the activity of standard anti-epileptic drugs against experimental seizures in rats

    Directory of Open Access Journals (Sweden)

    Dhande Priti

    2009-01-01

    Full Text Available Objectives : To study the effect of oral magnesium oxide supplementation alone and on the activity of standard anti-epileptic drugs in the animal models of maximal electroshock seizures (MES and chemically (pentylenetetrazole [PTZ]-induced seizures. Methods : Healthy male albino rats were given magnesium oxide (MgO supplementation orally in various doses (500, 750 and 1000 mg/kg /day for 4 weeks (day 1 to day 28. On day 0 and day 29, response to MES (180 mA for 0.2 s was tested 1 h after pre-administration of phenytoin or carbamazepine orally. Similarly, in the other groups, the response to PTZ 40 mg/kg i.p. was tested 1 h after pre-administration of oral sodium valproate. Results : Oral administration of MgO in a low dose (500 mg/kg for 4 weeks in healthy rats appears to exert protective effect against MES. High oral doses of MgO (750 and 1000 mg/kg appear to enhance the activity of phenytoin and carbamazepine in the MES model. MgO supplementation was seen to decrease the latency of PTZ-induced seizures. Conclusion : The dose of oral MgO appears to have an inverse relation with the protective effect in MES-induced seizure model. High doses of MgO supplementation given orally appear to enhance the activity of standard anti-epileptic drugs in the MES-induced seizure model.

  10. Drug interactions with the newer antiepileptic drugs (AEDs)--part 1: pharmacokinetic and pharmacodynamic interactions between AEDs.

    Science.gov (United States)

    Patsalos, Philip N

    2013-11-01

    Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide; 16 in total. Because often the treatment of epilepsy is lifelong, and because patients are commonly prescribed polytherapy with other AEDs, AED interactions are an important consideration in the treatment of epilepsy and indeed can be a major therapeutic challenge. For new AEDs, their propensity to interact is particularly important because inevitably they can only be prescribed, at least in the first instance, as adjunctive polytherapy. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. The principal pharmacokinetic interaction relates to hepatic enzyme induction or inhibition whilst pharmacodynamic interactions principally entail adverse effect synergism, although examples of anticonvulsant synergism also exist. Overall, the new AEDs are less interacting primarily because many are renally excreted or not hepatically metabolised (e.g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin) and most do not (or minimally) induce or inhibit hepatic metabolism. A total of 139 pharmacokinetic interactions between concurrent AEDs have been described. The least pharmacokinetic interactions (n ≤ 5) are associated with gabapentin, lacosamide, tiagabine, vigabatrin and zonisamide, whilst lamotrigine (n = 17), felbamate (n = 15), oxcarbazepine (n = 14) and rufinamide (n = 13) are associated with the most. To date, felbamate, gabapentin, oxcarbazepine, perampanel, pregabalin

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  12. Drug interactions with the newer antiepileptic drugs (AEDs)--Part 2: pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders.

    Science.gov (United States)

    Patsalos, Philip N

    2013-12-01

    Since antiepileptic drugs (AEDs) are prescribed to treat various non-epilepsy-related disorders in addition to the fact that patients with epilepsy may develop concurrent disorders that will need treatment, the propensity for AEDs to interact with non-AEDs is considerable and indeed can present a difficult clinical problem. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs (eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide) and drugs used to treat non-epilepsy disorders. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. Pharmacokinetic interactions relate to hepatic enzyme induction or inhibition and involved a variety of drugs including psychoactive drugs, cardioactive drugs, oral contraceptives, antituberculous agents, analgesics and antineoplastic drugs. A total of 68 pharmacokinetic interactions have been described, with lamotrigine (n = 22), topiramate (n = 18) and oxcarbazepine (n = 7) being associated with most, whilst lacosamide, pregabalin, stiripentol and vigabatrin are associated with none. Overall, only three pharmacodynamic interactions have been described and occur with oxcarbazepine, perampanel and pregabalin. PMID:23794036

  13. 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. PMID:24552078

  14. Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

    NARCIS (Netherlands)

    van der Heide, Mariska J.; Roze, Elise; van der Veere, Christa N.; ter Horst, Hendrik J.; Brouwer, Oebele F.; Bos, Arend F.

    2012-01-01

    Background: Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective: To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/met

  15. 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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive...... 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...

  17. 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.

  18. Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): evidence in humans and experimental models.

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  1. 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

    2016-09-01

    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.

  2. 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

    2016-09-01

    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. PMID:26939618

  3. Teratogenicity of Antiepileptic Medications

    OpenAIRE

    Benzi M Kluger; Meador, Kimford J.

    2008-01-01

    Antiepileptic drugs (AEDs) are frequently used to treat several conditions that are common in women of childbearing age, including epilepsy, headaches, and mood disorders. Moreover, as in the case of epilepsy and severe psychiatric disease, clinicians frequently do not have the option of stopping these medications or switching to another class of drugs. Overall, AEDs have been associated with an increased risk of major congenital malformations, minor anomalies, specific congenital syndromes, ...

  4. Comparing the effects of first-line antiepileptic drugs on the gait of dogs with idiopathic epilepsy.

    Science.gov (United States)

    Suiter, E J; Packer, R M A; Volk, H A

    2016-06-25

    Idiopathic epilepsy (IE) is a common chronic neurological disease of the dog. Previous studies of anti-epileptic drug (AED) treatment have indicated that acceptable AED adverse effects are as important to owners as reductions in seizure frequency. AEDs in both dogs and human beings are frequently associated with the adverse-effect ataxia. The aim of this study was to compare ataxia levels in dogs with IE treated chronically with phenobarbitone or imepitoin, the two currently available first-line AED treatments. The gait of 6 imepitoin-treated dogs, 8 phenobarbitone-treated dogs and 10 age-matched healthy control dogs were compared. Fifty strides from a walking gait were analysed for each dog, quantifying ataxia via the variability in six established gait parameters. Three variables differed significantly between groups: lateral distance between (i) pelvic paw placements, (ii) thoracic paw placements and (iii) stance time, which were significantly more variable in the phenobarbitone-treated dogs than imepitoin-treated or control dogs. These results indicate that dogs treated with phenobarbitone experience ataxia compared with controls and imepitoin-treated dogs. Conversely, there was no difference between imepitoin-treated dogs and controls. These results along with further research are needed to quantify AEDs adverse effects, to help vets and owners make more informed drug-choices. PMID:27302918

  5. 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.

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

    Science.gov (United States)

    Johannessen Landmark, Cecilie; Granas, Anne Gerd

    2016-01-01

    Introduction. Antiepileptic drugs (AEDs) are used to treat different conditions in elderly patients and are among the drug classes most susceptible to be involved in drug-drug interactions (DDI). The aim of the study was to describe and compare use of AEDs between home care service and nursing home patients, as these patients are not included in nationwide databases of drug utilization. In the combined population, we investigate DDI of AEDs with other central nervous system- (CNS-) active drugs and DDIs involving AEDs in general. Materials and Methods. Point-prevalence study of Norwegian patients in home care services and nursing homes in 2009. At the patient level, we screened for different DDIs involving AEDs. Results. In total, 882 patients (7.8%) of 11,254 patients used AEDs and number of users did not differ between home care services and nursing homes (8.2% versus 7.7%). In the combined population, we identified 436 potential DDIs in 45% of the patients. Conclusions. In a large population of elderly, home care service and nursing home patients do not differ with respect to exposure of AEDs but use more AEDs as compared to the general population of similar age. The risk of DDIs with AEDs and other CNS-active drugs should be taken into consideration and individual clinical evaluations are assessed in this population. PMID:27525114

  7. Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    OpenAIRE

    Luszczki Jarogniew J.; Marzeda Ewa; Kondrat-Wrobel Maria W.; Pyrka Daniel; Kocharov Sergey L.; Florek-Luszczki Magdalena

    2014-01-01

    The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl)- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock (MES)-induced tonic seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 ...

  8. Efficacy of Anti-Epileptic Drugs in the Treatment of Tumor and Its Associated Epilepsy: An in vitro Perspective.

    Science.gov (United States)

    Kaur, Taranjeet; Manchanda, Shaffi; Saini, Vedangana; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2016-03-01

    The change in the therapeutic targets from neuron to glia has proved beneficial in the treatment of many psychiatric disorders. The anti-epileptic drugs (AEDs) have been widely prescribed for the treatment of partial and complete seizures, bipolar disorder among others. The current study was carried out to explore the efficacy of some conventional and novel AEDs for the treatment of tumor-associated epilepsy which develops in 29-49% of the patients diagnosed with brain tumors. We used C6 glioma cell line as model system to study the effect of selected AEDs, viz., gabapentin (GBP), valproic acid (VPA) and topiramate (TPM). Morphometry, cell cycle analysis, apoptosis, expression of different protein markers, viz., GFAP, HSP70 and nuclear factor-κB (NFκB) were studied in AED-treated cultures. The study was further extended to rat hypothalamic primary explant cultures, and cell migration and expression of plasticity markers - neural cell adhesion molecule (NCAM) and polysialylation of NCAM (PSA-NCAM) - were studied in the explants. TPM was observed to show more pronounced increase in apoptosis of glioblastoma cells accompanied by significant downregulation in the expression of HSP70 and NFκB. TPM-treated explants also showed highest process ramification and cellular migration accompanied by intense expression of the plasticity markers as compared to those treated with GBP and VPA. Among the 3 AEDs tested, TPM was observed to show more promising effects on cytoprotection and plasticity of C6 glioma cells. PMID:27536020

  9. The effect of epilepsy and antiepileptic drugs on sexual, reproductive and gonadal health of adults with epilepsy.

    Science.gov (United States)

    Hamed, Sherifa A

    2016-06-01

    Epilepsy is a common chronic medical illness. Hyposexuality is the most frequent abnormality in men and women with epilepsy. In men with epilepsy, hypoandrogenimia, hypogonadism and sperm abnormalities are common. Testicular atrophy was also infrequently reported. In women with epilepsy, hyperandrogenism, polycystic ovaries (PCOs) and PCO syndrome are frequent. Decreased serum free testosterone, dehydroepiandrosterone levels, free androgen index and free testosterone/leutinizing hormone (LH) ratio and increased sex hormone binding globulin, estradiol, prolactin, LH, follicle stimulating hormone (FSH) levels and LH/FSH ratio are common with epilepsy. Disturbance of central and/or peripheral control of hypothalamic-pituitary-gonadal axis and alteration of central neurotrasmitters (GABA, glutamate and serotonin) by epileptic discharges or antiepileptic drugs (AEDs), direct gonadal toxicity by AEDs and pcyshicatric/psychosocial factors are all incriminated in sexual, reproductive and gonadal abnormalities associated with epilepsy. Patients may benefit from multidisplinary evaluation, tight seizure control, change the AED, androgen therapy, genital vasodilators, L-carnitine supplementation and psychotherapy. PMID:26934627

  10. Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.

    Directory of Open Access Journals (Sweden)

    Guanzhong Ni

    Full Text Available The aim of this study was to compare the serum levels of one-carbon metabolism (OCM nutrients (e.g., folate, homocysteine and vitamin B12 and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs and in healthy controls.In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA (n = 30 or lamotrigine (LTG (n = 30 monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05. No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001. The level of methylation of long interspersed nucleotide element-1 (LINE-1 in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01. A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023.Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

  11. Efficacy of Anti-Epileptic Drugs in the Treatment of Tumor and Its Associated Epilepsy: An in vitro Perspective.

    Science.gov (United States)

    Kaur, Taranjeet; Manchanda, Shaffi; Saini, Vedangana; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2016-03-01

    The change in the therapeutic targets from neuron to glia has proved beneficial in the treatment of many psychiatric disorders. The anti-epileptic drugs (AEDs) have been widely prescribed for the treatment of partial and complete seizures, bipolar disorder among others. The current study was carried out to explore the efficacy of some conventional and novel AEDs for the treatment of tumor-associated epilepsy which develops in 29-49% of the patients diagnosed with brain tumors. We used C6 glioma cell line as model system to study the effect of selected AEDs, viz., gabapentin (GBP), valproic acid (VPA) and topiramate (TPM). Morphometry, cell cycle analysis, apoptosis, expression of different protein markers, viz., GFAP, HSP70 and nuclear factor-κB (NFκB) were studied in AED-treated cultures. The study was further extended to rat hypothalamic primary explant cultures, and cell migration and expression of plasticity markers - neural cell adhesion molecule (NCAM) and polysialylation of NCAM (PSA-NCAM) - were studied in the explants. TPM was observed to show more pronounced increase in apoptosis of glioblastoma cells accompanied by significant downregulation in the expression of HSP70 and NFκB. TPM-treated explants also showed highest process ramification and cellular migration accompanied by intense expression of the plasticity markers as compared to those treated with GBP and VPA. Among the 3 AEDs tested, TPM was observed to show more promising effects on cytoprotection and plasticity of C6 glioma cells.

  12. Preclinical evaluation of 2,2,3,3-tetramethylcyclopropanecarbonyl-urea, a novel, second generation to valproic acid, antiepileptic drug.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Steve White, H; Wilcox, Karen S; Lamb, John G; Pappo, Orit; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2006-09-01

    2,2,3,3-Tetramethylcyclopropanecarbonylurea (TMCU) is an amide derivative of a tetramethylcyclopropyl analogue of valproic acid (VPA), one of the leading antiepileptic drugs. Structural considerations used in the design of TMCU aimed to enhance the anticonvulsant potency of VPA and to prevent its two life-threatening side effects; i.e., teratogenicity and hepatotoxicity. The anticonvulsant activity of TMCU was evaluated in the MES, scMet, 6-Hz, scBic and scPic tests, and also in the hippocampal kindling model of partial seizures and lamotrigine-resistant amygdala kindling model of therapy-resistant seizures. Minimal motor impairment was determined using the rotorod test in mice and the positional sense test, muscle tone test, and gait and stance test in rats. The antinociceptive effect of TMCU was evaluated in the mouse formalin model of acute-tonic pain. The molecular mechanisms of action of TMCU were investigated in electrophysiological studies using the whole-cell patch-clamp technique. Teratogenicity studies were performed in a SWV/Fnn-mouse model of VPA-induced teratogenicity. TMCU hepatotoxicity was evaluated following 1-week intraperitoneal and oral administration of 50, 250 and 500 mg/kg doses to rats. In the hepatotoxicity study the blood levels of TMCU were evaluated at day 1 and day 7 of the treatment. TMCU mutagenicity was evaluated in the Ames test.

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

    Directory of Open Access Journals (Sweden)

    Dersh Jeffrey J

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gibsi P. Rocha

    2004-04-01

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

  15. Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

    Science.gov (United States)

    Leclercq, Karine; Kaminski, Rafal M

    2015-08-01

    Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Bipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel...... chloride (0.9 mg/kg) and lamotrigine (20 mg/kg), which are known to effectively stabilize mood in humans, both significantly decreased AMPH+CDP-induced locomotor activity without affecting basal locomotor activity. The results furthermore indicate that retigabine, like lithium and lamotrigine...

  17. 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.

  18. 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.

  19. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero

    Directory of Open Access Journals (Sweden)

    Arulmozhi T

    2006-01-01

    Full Text Available Objective: To evaluates the physical growth and psychomotor development of infants born to women with epilepsy on regular Anti Epileptic Drugs (AEDs. Setting: Govt. Stanley Medical College and Hospital, Tertiary care referral centre, Chennai. Design: Open prospective cohort study with a control group. Materials and Methods: 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. Results : 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 P P P monotherapy had a negative impact on sitting progression. Conclusion : 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 prone progression which alone improved by 12th month. Phenytoin exposure in utero resulted in large AF and it had a negative impact on sitting progression in comparison with Carbamazepine and Sodium valproate.

  20. Identification of phototransformation products of the antiepileptic drug gabapentin: Biodegradability and initial assessment of toxicity.

    Science.gov (United States)

    Herrmann, Manuel; Menz, Jakob; Olsson, Oliver; Kümmerer, Klaus

    2015-11-15

    The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 μg L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic

  1. 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

  2. ACEA (a highly selective cannabinoid CB1 receptor agonist) stimulates hippocampal neurogenesis in mice treated with antiepileptic drugs.

    Science.gov (United States)

    Andres-Mach, Marta; Haratym-Maj, Agnieszka; Zagaja, Miroslaw; Rola, Radoslaw; Maj, Maciej; Chrościńska-Krawczyk, Magdalena; Luszczki, Jarogniew J

    2015-10-22

    Hippocampal neurogenesis plays a very important role in learning and memory functions. In a search for best neurological drugs that protect neuronal cells and stimulate neurogenesis with no side effects, cannabinoids proved to be a strong group of substances having many beneficial properties. The aim of this study was to evaluate the impact of ACEA (arachidonyl-2'-chloroethylamide--a highly selective cannabinoid CB1 receptor agonist) combined with a classical antiepileptic drug sodium valproate (VPA) on neural precursor cells' proliferation and differentiation in the mouse brain. All experiments were performed on adolescent CB57/BL male mice injected i.p. with VPA (10mg/kg), ACEA (10mg/kg) and PMSF (30 mg/kg) (phenylmethylsulfonyl fluoride--a substance protecting ACEA against degradation by the fatty-acid amidohydrolase) for 10 days. Next an acute response of proliferating neural precursor cells to ACEA and VPA administration was evaluated with Ki-67 staining (Time point 1). Next, in order to determine whether acute changes translated into long-term alterations in neurogenesis, proliferating cells were labeled with 5-bromo-2deoxyuridine (BrdU) followed by confocal microscopy used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes (Time point 2). Results indicate that ACEA with PMSF significantly increase the total number of Ki-67-positive cells when compared to the control group. Moreover, ACEA in combination with VPA increased the number of Ki-67-positive cells, whereas VPA administered alone had no impact on proliferating cells' population. Accordingly, neurogenesis study results indicate that the combination of ACEA+PMSF administered alone and in combination with VPA considerably increases the total number of BrdU-positive cells in comparison to the control group while ACEA+PMSF alone and in combination with VPA increased total numbers of BrdU-positive cells, newly born neurons and astrocytes as compared to VPA group but not to

  3. 抗癫痫药基因多态性研究进展%Research on genetic polymorphism of antiepileptic drugs

    Institute of Scientific and Technical Information of China (English)

    高森

    2014-01-01

    Clinical agrees that drug's gene polymorphism has important meaning for individual differences of antiepileptic drugs, gene polymorphism leads individuals appear different pharmacological and toxicological effects. Pharmacogenetics is a genetics discipline, along with in-depth study of pharmacogenetics, personalized medicine has a new situation. This paper firstly analyzes the types and the effect of antiepileptic drugs, then discusse gene polymorphism on epilepsy medicine clinical research progress.%临床医学上一致认为药物的基因多态性对于抗癫痫药的个体差异有着重要的意义,基因多态性导致个体出现不同的药理和毒理作用。遗传药理学是一门遗传学学科,随着人们对遗传药理学的深入研究,个体化用药有了新的局面。本文首先分析了抗癫痫药的种类及其疗效,然后详细介绍了当前基因多态性对抗癫痫药疗效研究进展。

  4. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model.

    Science.gov (United States)

    Bogdanović, Renée Marie; Syvänen, Stina; Michler, Christina; Russmann, Vera; Eriksson, Jonas; Windhorst, Albert D; Lammertsma, Adriaan A; de Lange, Elisabeth C; Voskuyl, Rob A; Potschka, Heidrun

    2014-10-01

    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  5. 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

  6. N-valproyl-L-phenylalanine as new potential antiepileptic drug: synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy.

    Science.gov (United States)

    De Caro, Viviana; Scaturro, Anna Lisa; Sutera, Flavia Maria; Avellone, Giuseppe; Schiera, Gabriella; Ferrantelli, Evelina; Carafa, Maria; Rizzo, Valerio; Carletti, Fabio; Sardo, Pierangelo; Giannola, Libero Italo

    2014-01-01

    Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, MS, (13)C and (1)H- NMR analyses. The Log D(pH7.4) value (0.19) indicated that new molecule was potentially able to cross biological membranes. The resistance to chemical and enzymatic hydrolysis of N-valproyl-L-phenylalanine was also assessed. All trials suggested that the compound, at the pH conditions of the entire gastro-intestinal tract, remained unmodified. Furthermore, the new compound did not undergo enzymatic cleavage both in plasma and in cerebral medium up to 24 h. The toxicity assay on primary cultures of astrocytes indicated that the synthetized conjugate was less toxic than both free VPA and L-Phenylalanine. In this paper, the anticonvulsant activity of the new compound against epileptic burst discharges evoked in vitro in rat hippocampal slices was also evaluated. These preliminary results underline that N-valproyl-L-phenylalanine as new potential antiepileptic agent could represent a good candidate to further investigations.

  7. 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.

  8. 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. PMID:25846035

  9. Simultaneous analysis of 22 antiepileptic drugs in postmortem blood, serum and plasma using LC-MS-MS with a focus on their role in forensic cases.

    Science.gov (United States)

    Deeb, Shaza; McKeown, Denise A; Torrance, Hazel J; Wylie, Fiona M; Logan, Barry K; Scott, Karen S

    2014-10-01

    In recent years, there has been a growth in reports of antiepileptic drugs (AEDs) being misused on their own or in combination with other drugs of abuse in a variety of toxicological case types such as drug abuse, suicide, overdose and drug facilitated crime. To our knowledge, there are no simultaneous quantification methods for the analysis of the most commonly encountered AEDs in postmortem whole blood and clinical plasma/serum samples at the same time. A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric (LC-MS-MS) method has been developed and validated for the simultaneous quantification of carbamazepine (CBZ) and its metabolite CBZ-10,11-epoxide, eslicarbazepine acetate, oxcarbazepine and S-licarbazepine as a metabolite, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, phenobarbital, phenytoin and its metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin, retigabine (ezogabine) and its metabolite N-acetyl retigabine, rufinamide, stiripentol, topiramate, tiagabine, valproic acid, vigabatrin and zonisamide in postmortem whole blood, serum and plasma which would be suitable for routine forensic toxicological analysis and therapeutic drug monitoring. All AEDs were detected and quantified within 17 min without endogenous interferences. The correlation coefficient (R(2)) was >0.995 for all AEDs with accuracy ranging from 90 to 113% and precision <13% for all analytes. The recovery ranged from 70 to 98%. No carryover was observed in a blank control injected after the highest standard and the matrix effect was acceptable and ranged from 90 to 120%. The method has been successfully verified using authentic case samples that had previously been quantified using different methods. PMID:25217536

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

    Directory of Open Access Journals (Sweden)

    Hubertus Himmerich

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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. Knockout of P-glycoprotein does not alter antiepileptic drug efficacy in the intrahippocampal kainate model of mesial temporal lobe epilepsy in mice.

    Science.gov (United States)

    Bankstahl, Marion; Klein, Sabine; Römermann, Kerstin; Löscher, Wolfgang

    2016-10-01

    Pharmacoresistance to antiepileptic drugs (AEDs) is a major challenge in epilepsy therapy, affecting at least 30% of patients. Thus, there is considerable interest in the mechanisms responsible for such pharmacoresistance, with particular attention on the specific cellular and molecular factors that lead to reduced drug sensitivity. Current hypotheses of refractory epilepsy include the multidrug transporter hypothesis, which posits that increased expression or function of drug efflux transporters, such as P-glycoprotein (Pgp), in brain capillaries reduces the local concentration of AEDs in epileptic brain regions to subtherapeutic levels. In the present study, this hypothesis was addressed by evaluating the efficacy of six AEDs in wildtype and Pgp deficient Mdr1a/b(-/-) mice in the intrahippocampal kainate model of mesial temporal lobe epilepsy. In this model, frequent focal electrographic seizures develop after an initial kainate-induced status epilepticus. These seizures are resistant to major AEDs, but the mechanisms of this resistance are unknown. In the present experiments, the focal nonconvulsive seizures were resistant to carbamazepine and phenytoin, whereas high doses of valproate and levetiracetam exerted moderate and phenobarbital and diazepam marked anti-seizure effects. All AEDs suppressed generalized convulsive seizures. No significant differences between wildtype and Pgp-deficient mice were observed in anti-seizure drug efficacies. Also, the individual responder and nonresponder rates in each experiment did not differ between mouse genotypes. This does not argue against the multidrug transporter hypothesis in general, but indicates that Pgp is not involved in the mechanisms explaining that focal electrographic seizures are resistant to some AEDs in the intrahippocampal mouse model of partial epilepsy. This was substantiated by the finding that epileptic wildtype mice do not exhibit increased Pgp expression in this model. PMID:27288003

  13. 4城市2011-2013年抗癫痫类药物使用情况的分析与比较%The Analysis and Comparison of Four Cities Antiepileptic Drug Use in 2011-2013

    Institute of Scientific and Technical Information of China (English)

    王佳庆; 王莉文; 赵志刚

    2014-01-01

    Objective:Analyzing the Antiepileptic drug use situation in four cities:Beijing, Shanghai, Guangzhou, Chengdu in 2011-2013. Methods:Antiepileptic drug use from four cities in 2011-2013 was analyzed by using Microsoft office access 2007 software. Results:There are more men than women in these four cities for antiepileptic drug use in 2011-2013;the age distribution is quite different;and there is small defined daily dose and frequency difference. Conclusion:DDD and DDDs in four cities are basically the same, and drug use is fairly standard.%目的:研究北京、上海、广州、成都四个城市2011-2013年抗癫痫类药物用药情况。方法:利用Microsoft Office Access 2007软件对2011-2013年四个城市抗癫痫类药物用药进行统计分析。结果:四个城市2011-2013年抗癫痫类用药患者男性高于女性,年龄分布有较大差异,限定日剂量及用药频度差异较小。结论:四个城市用药限定日剂量及用药频度基本一致,药物使用比较规范。

  14. The analysis of 75 cases of drug addicts swallowed abnormal substance will be given compelled detoxification%75例拟强戒吸毒人员吞食异物情况分析

    Institute of Scientific and Technical Information of China (English)

    王庆珍; 王博; 宗建强

    2015-01-01

    Objective:To investigate and analyze the condition of drug addicts swallowed abnormal substance who will be given compelled separation and detoxification,then to put in corresponding measures. Methods:Through checking on 1072 cases of drug ad-dicts will be given compelled separation and detoxification,we find 75 cases of them swallowed abnormal substance and obviously af-fected their compelled detoxification,then the related data are retrospectively analyzed. Results:The drug addicts swallowed abnormal substance are more common in males,mainly of young people,and low level of culture. Their motivation and in order to avoid com-pelled detoxification. Meanwhile we find the kinds of abnormal substance are diversified and complicated. Conclusion:We need strengthen the propaganda work about the harm of drugs,and the program control. The additional punishment should be given to those swallowed abnormal substance,so as to block the adverse example effect.%目的:调查分析拟强制隔离戒毒吸毒人员吞食异物情况,提出应对措施。方法:对拟强制隔离戒毒的吸毒人员1072例进行相关检查,检出有吞食异物且影响强制戒毒的人员75例,对相关资料进行回顾性分析。结果:吞食异物者男性居多、以青壮年为主,且文化水平偏低。其主要动机是逃避强制戒毒治疗。吞食异物种类复杂。结论:应加大毒品危害等相关知识的宣传工作,强化环节控制,建议对吞食异物者追加处罚、阻断不良示范效应。

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

    Directory of Open Access Journals (Sweden)

    Hui Li

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

  16. Effect of N-(m-bromoanilinomethyl-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    Directory of Open Access Journals (Sweden)

    Luszczki Jarogniew J.

    2014-06-01

    Full Text Available The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA] in the mouse maximal electroshock (MES-induced tonic seizure model. Tonic hind limb extension (seizure activity was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration delivered via ear-clip electrodes. BAM-IPPS administered (i.p. at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05. Lower doses of BAM-IPPS (50 and 100 mg/kg had no significant impact on the threshold for electroconvulsions in mice. Moreover, BAM-IPPS (100 mg/kg did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the mouse MES model. BAM-IPPS elevated the threshold for electroconvulsions in mice in a dosedependent manner. However, BAM-IPPS (100 mg/kg did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of BAM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.

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

    Science.gov (United States)

    Edwin, Bismi; Joe, I. Hubert

    2013-10-01

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

  18. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    Science.gov (United States)

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  19. A Compelling Desire for Deafness

    Science.gov (United States)

    Veale, David

    2006-01-01

    A case is described of a patient who has a compelling and persistent desire to become deaf. She often kept cotton wool moistened with oil in her ears and was learning sign language. Living without sound appeared to be a severe form of avoidance behavior from hyperacusis and misophonia. She had a borderline personality disorder that was associated…

  20. Determination of anti-anxiety and anti-epileptic drugs in hospital effluent and a preliminary risk assessment.

    Science.gov (United States)

    de Almeida, Carlos Alberto A; Brenner, Carla G B; Minetto, Luciane; Mallmann, Carlos A; Martins, Ayrton F

    2013-11-01

    In this study, an analytical methodology was developed for the determination of psycho-active drugs in the treated effluent of the University Hospital at the Federal University of Santa Maria, RS - Brazil. Samples were collected from point A (Emergency) and point B (General effluent). The adopted methodology included a pre-concentration procedure involving the use of solid phase extraction and determination by liquid chromatography coupled to mass spectrometry. The limit of detection for bromazepam and lorazepam was 4.9 ± 1.0 ng L(-1) and, for carbamazepine, clonazepam and diazepam was 6.1 ± 1.5 ng L(-1). The limit of quantification was 30.0 ± 1.1 ng L(-1), for bromazepam, clonazepam and lorazepam; for carbamazepine was 50.0 ± 1.8 ng L(-1) and was 40.0 ± 1.0 ng L(-1) for diazepam. The mean concentrations in the Emergency and General effluent treated currents were as follows: for bromazepam, 195 ± 6 ng L(-1) and 137 ± 7 ng L(-1); for carbamazepine, 590 ± 6 ng L(-1) and 461 ± 10 ng L(-1); for diazepam, 645 ± 1 ng L(-1) and 571 ± 10 ng L(-1); for lorazepam, 96 ± 7 ng L(-1) and 42 ± 4 ng L(-1); and for clonazepam, 134 ± 10 ng L(-1) and 57 ± 10 ng L(-1). A preliminary risk assessment was conducted: carbamazepine and diazepam require considerable attention owing to their environmental toxicity. The occurrence of these psychoactive-drugs and the environmental risks that they pose demonstrated the need for a more efficient treatment system. As far we are aware, there have been no comparable studies to this on the hazards of hospital effluents in Brazil, and very few that have carried out a risk assessment of psycho-active drugs in hospital effluent in general. PMID:24034828

  1. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model

    OpenAIRE

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Kondrat-Wrobel, Maria W.; Tutka, Piotr; Jarogniew J Luszczki

    2014-01-01

    The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were...

  2. Zebrafish larvae exposed to ginkgotoxin exhibit seizure-like behavior that is relieved by pyridoxal-5′-phosphate, GABA and anti-epileptic drugs

    Directory of Open Access Journals (Sweden)

    Gang-Hui Lee

    2012-11-01

    The etiology of epilepsy is a very complicated, multifactorial process that is not completely understood. Therefore, the availability of epilepsy animal models induced by different mechanisms is crucial in advancing our knowledge and developing new therapeutic regimens for this disorder. Considering the advantages of zebrafish, we have developed a seizure model in zebrafish larvae using ginkgotoxin, a neurotoxin naturally occurring in Ginkgo biloba and hypothesized to inhibit the formation of the neurotransmitter γ-aminobutyric acid (GABA. We found that a 2-hour exposure to ginkgotoxin induced a seizure-like behavior in zebrafish larvae. This seizure-like swimming pattern was alleviated by the addition of either pyridoxal-5′-phosphate (PLP or GABA and responded quickly to the anti-convulsing activity of gabapentin and phenytoin, two commonly prescribed anti-epileptic drugs (AEDs. Unexpectedly, the ginkgotoxin-induced PLP depletion in our experimental setting did not affect the homeostasis of folate-mediated one-carbon metabolism, another metabolic pathway playing a crucial role in neural function that also relies on the availability of PLP. This ginkgotoxin-induced seizure behavior was also relieved by primidone, which had been tested on a pentylenetetrazole-induced zebrafish seizure model but failed to rescue the seizure phenotype, highlighting the potential use and complementarity of this ginkgotoxin-induced seizure model for AED development. Structural and morphological characterization showed that a 2-hour ginkgotoxin exposure did not cause appreciable changes in larval morphology and tissues development. In conclusion, our data suggests that this ginkgotoxin-induced seizure in zebrafish larvae could serve as an in vivo model for epileptic seizure research and potential AED screening.

  3. 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.

  4. The antiepileptic drug on pregnant women with epilepsy%育龄妇女抗癫痫药的合理使用

    Institute of Scientific and Technical Information of China (English)

    王宇卉

    2015-01-01

    育龄妇女的抗癫痫治疗对临床医生是一个挑战,必须考虑很多问题.癫痫女性(WWE)怀孕期间终止甚或改变抗癫痫药(AEDs)方案很危险,可能导致母亲和胎儿的损害或死亡;少数情况下,中断AEDs似乎合理,但多数在孕期需要继续使用AEDs.怀孕期间AEDs的代谢可能发生很大变化,对WWE后代的风险包括特定AED的不良反应风险以及癫痫发作本身的风险,很多AEDs有众所周知的致畸作用,还有产科并发症、新生儿预后不良、先天性畸形,甚至对孩子随后的认知功能有风险.必须告知其相关风险,适当地指导其治疗,孕前优化癫痫治疗、选择最有效的 AEDs以控制癫痫,尽可能用单药治疗且用最小有效量,避免多药治疗和丙戊酸,补充叶酸,最大限度地控制癫痫发作并降低风险.%The treatment of pregnant women with epilepsy (WWE) is a challenge to the clinician, and many questions must be considered. In women with proven epilepsy, it may be dangerous to stop or even change the antiepileptic drug (AED) regimen during pregnancy. Changes could lead to injury or death in both the mother and the fetus. In the rare cases when discontinuing an AED is plausible, but most WWE are consigned to continue their AEDs before, during and after pregnancy. The metabolism of AEDs may change drastically during pregnancy, the risks to the fetus must be delineated in terms of side effects from specific drugs as well as risks from the seizure disorder itself. Many AEDs have well known teratogenic effects, there are risks for obstetrical complications, poor neonatal outcomes, congenital malformations and even cognitive effects on the child later in life. These must be elucidated to the mother. Recommendations include but are not limited to preconception counseling, prescribing the most effective AED while minimizing risks, avoiding poly therapy and valproate if possible, and taking folate pre- and post-conception.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Fei Zhu

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  8. 肝药酶CYP3A4与抗癫(癎)药物的代谢研究进展%Progress on the metabolism of antiepileptic drugs by human hepatic CYP3A4 enzymes

    Institute of Scientific and Technical Information of China (English)

    张君梅

    2011-01-01

    癫(癎)是危害人类健康的常见神经系统疾病,临床常用抗癫(癎)药多通过细胞色素P450等肝药酶代谢.CYP3A4是P450酶系中最重要的代谢酶,参与40%~60%的药物代谢,与临床常用抗癫(癎)药的代谢也有非常紧密的关系.该文对CYP3A4的一般特性及其与抗癫(癎)药物的代谢研究进展作一概述.%Epilepsy is a common disease in nervous system.Most antiepileptic drugs are metabolized by liver enzymes.such as cytochrome P450 enzyme.CYP3A4 iS the most important enzyme in P450 family.involved in the metabolism of about 40%~60% of the drugs use for clinic.It also has a close relationship with the metabolism of antiepileptie drugs.This review summarizes the general characteristic of CYP3A4 and itsrelationship with the metabolism of antiepileptic drugs.

  9. Effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the protective action of various antiepileptic drugs in the maximal electroshock-induced seizure model: a type II isobolographic analysis

    OpenAIRE

    Andres-Mach, Marta; Zadrożniak, Anna; Haratym-Maj, Agnieszka; Florek-Luszczki, Magdalena; Raszewski, Grzegorz; Antkiewicz-Michaluk, Lucyna; Jarogniew J Luszczki

    2013-01-01

    The aim of this study was to characterize the interaction between 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ—an endogenous parkinsonism-preventing substance) and various antiepileptic drugs [AEDs: clonazepam (CZP), ethosuximide (ETS), gabapentin (GBP), levetiracetam (LEV), tiagabine (TGB) and vigabatrin (VGB)] in the mouse maximal electroshock (MES)-induced seizure model. Results indicate that 1-MeTHIQ in combination with CZP (at the fixed ratios of 50:1 and 25:1), ETS (1:10) and GBP (...

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

    Directory of Open Access Journals (Sweden)

    Lu Ban

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

  11. Epilepsy, hormones, and antiepileptic drugs

    OpenAIRE

    2010-01-01

    LIST OF PAPERS 1) Svalheim S, Taubøll E, Bjørnenak T, Røste LS, Mørland T, Sætre ER, Gjerstad L. Do women with epilepsy have increased frequency of menstrual disturbances? Seizure 2003; 12:529-533. doi:10.1016/S1059-1311(03)00195-X 2) Svalheim S, Taubøll E, Bjørnenak T, Røste LS, Mørland T, Sætre ER, Gjerstad L. Onset of epilepsy and menarche--is there any relationship? Seizure 2006; 15:571-575. doi:10.1016/j.seizure.2006.07.003 3) Svalheim S, Taubøll E, Surdova K, Ormel L, Dahl...

  12. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents

    OpenAIRE

    Rigo, J-M; Hans, G.; Nguyen, L.; Rocher, V; Belachew, S; Malgrange, B; Leprince, P.; Moonen, G.; Selak, I; Matagne, A; Klitgaard, H

    2002-01-01

    In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra®) may involve modulation of inhibitory neurotransmission.GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compar...

  13. Clinical and EEG features in children with febrile seizures after antiepileptic drug therapy%口服抗癫癇药物治疗儿童热性惊厥的临床与脑电图分析

    Institute of Scientific and Technical Information of China (English)

    邱鹏玲; 施亿赟; 孙道开; 王艺

    2011-01-01

    目的 了解有癫癇高危因素的热性惊厥患儿应用丙戊酸钠与托吡酯口服治疗4年的临床与脑电图改变情况.方法 对2004~2005年的132例有应用抗癫癇药物指征的热性惊厥患儿给予丙戊酸钠与托吡酯口服治疗,每半年随访一次病情变化、血常规和肝肾功能;每一年随访一次睡眠脑电图.共随访4年.结果 随访时间1~10年,丙戊酸钠口服液单药治疗110例,长期控制率为98.2%,95例已停药,10例正处在减药过程中.托吡酯单药治疗13例,均发作控制,顺利停药.无一例出现血常规和肝肾功能异常表现.治疗后睡眠脑电图恢复正常者102例,出现局灶性改变者8例,两侧同步性棘慢波4例,3 Hz棘慢波及多棘慢波2例.结论 对于癫癇高危因素的热性惊厥患儿,早期使用抗癫癇药物丙戊酸钠或托吡酯.疗效确切,无明显不良反应.抗癫癇药物治疗后大部分患儿睡眠脑电图恢复正常.%Objective To investigate the changes of clinical and EEG features in children with febrile seizures which are prone to epilepsy four years after antiepileptic drugs valproate and/or topiramate treatment . Methods One hundred and thirty-two children with febrile seizures between 2004 and 2005 and who had the indications of antiepileptic drugs treatment were administered with oral valproate and/or topiramate treatment. The children were followed up for four years.Routine blood tests, liver and renal function tests were performed twice a year. Sleeping activation EEG examination was performed once a year. Results During the follow-up of 1 to 10 years, 108 (98.2%) out of 110 children with valproate monotherapy were seizure-free. In the 110 cases, 95 were in the drug withdrawl and 10 were in the drug reduction. All of 13 cases receiving topiramate monotherapy were seizure-free and were in the drug withdrawl. None of the patients showed abnormalities in routine blood tests, liver and renal functions tests. Sleeping

  14. MK-801与抗癫痫药合用对大鼠杏仁核点燃的影响%Effect of combination of dizocilpine with general antiepileptic drugs on amygdala kindling models in rats

    Institute of Scientific and Technical Information of China (English)

    仲伟珍; 赵永娟; 高桂梅; 杨志宏; 岳旺

    2004-01-01

    目的在大鼠杏仁核点燃模型研究MK-801(地佐西平)及其联合用药的抗癫痫作用.方法建立大鼠杏仁核慢性电刺激点燃模型,测定不同剂量的MK-801对点燃模型各项指标的影响,探讨MK-801与其他抗癫痫药的协同作用,用氨基脲诱发的小鼠惊厥模型测定MK-801抗惊厥作用. 结果 MK-801(0.1~0.25 mg·kg-1)可剂量依赖性抑制杏仁核点燃,缩短后放电时程,降低Racine's分级;在对点燃均无明显影响的剂量下,MK-801(0.05 mg·kg-1)与抗癫痫药(苯巴比妥、丙戊酸及尼卡地平)合用可缩短后放电时程或降低Racine's分级.MK-801(0.1~0.25 mg·kg-1)显著降低小鼠氨基脲诱发的发作潜伏期、惊厥发生率和死亡率.结论 MK-801具有抑制大鼠杏仁核点燃的作用,增强苯巴比妥、丙戊酸及尼卡地平的抗癫痫活性,为临床的合并用药提供实验依据.%Aim To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs. Methods To establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose. The influence of dizocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observed. Results Dizocilpine (0.1-0.25 mg·kg-1, ip) was shown to dose-dependently inhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P<0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P<0.01). Dizocilpine (0.1-0.25 mg·kg-1, ip) significantly prolonged the latency and reduced the rate of convulsions and death in mice. Conclusion Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital

  15. 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…

  16. Switching to generic anti-epileptic medicines : A regulatory perspective

    NARCIS (Netherlands)

    Maliepaard, Marc; Hekster, Yechiel A.; Kappelle, Arnoud; Van Puijenbroek, Eugène P.; Elferink, André J.; Welink, Jan; Gispen-de Wied, Christine C.; Lekkerkerker, Frits J.F.

    2010-01-01

    Introduction: Currently, there is a lot of discussion about whether generic substitution of anti-epileptic drugs (AEDs) with the same active moiety but from different manufacturers can take place safely. Many AEDs are considered to have a narrow therapeutic index, and the consequences of an epilepti

  17. Estabilishment of antiepileptic drug resistant model and its P-gp expression in rats%抗癫(癎)药耐药性鼠模型的建立及其P-gp的表达

    Institute of Scientific and Technical Information of China (English)

    刘晓英; 伍国锋; 郝勇; 陈文珍; 洪震

    2011-01-01

    Objective;To establish the antiepileptic drug-resistan model and to observe the expression of P-glycoprotein(P-gp)in rats. Methods.- The epileptic rat model were first with lithium chloride-pi-locarpine to induce epilepsy in rats. Then the antiepileptic drug resistant model were screened out with phenytoin from established rat models. RT-PCR, Western Blot and immunohistochemical staining was carried out to present expression of P-gp in different loci of the rat brains. Results; It was identified by clinical scoring and EEG that the pbarmaoresistantKor refractory) epilepstic models were successfully established with this method. The P-gp expressions in the hipocampus, cerebellum and cortex were all higher in refractory epileptic rats than those in the normal and non-refractory rats. Conclusions: Lithium-pilocarpine and drug-screening can be used to produce the refractory epilepsy models. The expression of P-gp in refractory epilepsy model rats is heightened significantly.%目的:建立抗癫(癎)药(AED)耐药性大鼠模型,并观察其P-糖蛋白(P-gp)的表达.方法:首先应用氯化锂-匹罗卡品诱导癫(癎)鼠模型,然后在此基础上进一步用苯妥英钠药物筛选的方法获得AED的耐药性大鼠模型.通过RT-PCR、蛋白印迹法(Western Blot)和免疫组化等方法研究P-gp在该动物模型脑内不同部位的表达.结果:应用氯化锂-匹罗卡品诱导的癫(癎)鼠模型进行药物筛选的方法成功获得了AED耐药性癫(癎)动物模型,并经临床评分和脑电图证实.耐药性癫痫(癎)模型大鼠海马、小脑及大脑皮层的P-gp表达水平均显著高于非耐药性癫(癎)大鼠及正常对照大鼠.结论:对氯化锂-匹罗卡品诱导的鼠模型进行药物筛选的方法可建立AED耐药性癫(癎)动物模型;P-gp 在AED耐药性癫(癎)大鼠脑内表达水平显著升高.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Compelling Diversities, Educational Intersections: Policy, Practice, Parity

    Science.gov (United States)

    Taylor, Yvette

    2013-01-01

    The ninth international Gender and Education Association Conference "Compelling Diversities, Educational Intersections" hosted by the Weeks Centre for Social and Policy Research, London South Bank University engages with key debates surrounding the interplay between dynamics of education, work, employment and society in the context of…

  1. 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 rate of gastric emptying or an effect directly on the absorption of vigabatrin, possibly via inhibition of PAT1 or another drug transporter. In conclusion, co-administration of PAT1-ligands together with vigabatrin did not significantly alter the pharmacokinetic profile of vigabatrin....

  2. Study of factors responsible for recurrence of seizures in controlled epileptics for more than 1 years after withdrawal of antiepileptic drugs.

    Directory of Open Access Journals (Sweden)

    Lamdhade S

    2002-07-01

    Full Text Available 531 epileptic patients, who had achieved remission mostly for 2 years or more were studied. The mean follow up period was 5 years. Recurrence was noted in 103 patients (19% after gradual withdrawal of AED, over a period of 3-4 months. 424 patients (81% did not have recurrence. The recurrence rate was influenced adversely by factors like adolescent age and later onset seizures, pre-treatment duration of symptoms more than 3 years, pre-treatment precipitating factors like emotional stress, lack of sleep and meals (however, number in each group is small, positive family history of epilepsy, focal neurodeficit, absence and myoclonic plus grandmal type of clinical seizures, paroxysmal generalized spike and wave discharges and generalized short polyspike and wave discharges in the pretreatment EEG, atrophic changes on CT brain scan (in small numbers, head trauma at birth or later and hereditary factors as etiology of epilepsy, and more than 30 number of seizures before achieving the remission. Factors like, sex, frequency of seizures, period of remission i.e. two years or more and number of drugs used to achieve remission, did not have any significant adverse effect. However, in the last parameter 95% remission was achieved by one or a combination of two drugs (72% and 23% respectively.

  3. The Retention Rate of Treatment and Long-term Tolerability of the New Type of Antiepileptic Drugs%新型抗癫痫药物治疗保留率及长期耐受性的研究

    Institute of Scientific and Technical Information of China (English)

    林旭; 卢秀英; 伍雪英; 何进宇; 周东

    2016-01-01

    目的 研究5种新型抗癫痫用药(拉莫三嗪、托吡酯、奥卡西平、左乙拉西坦和加巴喷丁)治疗的保留率及耐受性.方法 纳入2012年10月-2014年10月216例癫痫患者.经长程视频脑电监测确诊为癫痫的患者随机分入5个治疗组(拉莫三嗪组57例,托吡酯组42例,奥卡西平组49例,左乙拉西坦组47例,加巴喷丁组21例),分别予相应的5种药物口服治疗.每4周通过电话或面谈进行随访,记录发作的减少情况、不良反应以及放弃治疗的患者情况.按以下公式计算每次随访的保留率:当前的服药人数/该药的起始人组人数×100%.观察随访结束后,采用Kaplan-Meire生存曲线和Cox比例风险模型进行相关统计学分析.结果 经过观察随访,拉莫三嗪组的最终保留率最高(85.9%)、加巴喷丁组最低(14.3%);绝大部分患者在坚持服药24周后都能坚持服药到观察结束;导致停药的常见原因依次为:无效、皮疹、镇静和行为激越不良反应.结论 新型抗癫痫药物治疗保留率与药物疗效、不良反应的种类及个体耐受情况、获得药物的途径便利性、服药的个体偏好等因素相关.%Objective To evaluate the treatment retention rate of five new types of antiepileptic drugs:lamotrigine (LTG),topiramate (TPM),oxcarbazepine (OXC),levetiracetam (LEV) and gabapentin (GBP) and their tolerability.Methods A total of 216 patients diagnosed as epilepsy by receiving the long-term video electroencephalography monitoring between October 2012 and October 2014 were randomized into five drug treatment groups (LTG,n=57;TPM,n=42;OXC,n=49;LEV,n=47;GBP,n=21) and received corresponding dose of drug therapy.The seizure frequency,adverse events and number of patients giving up therapy were collected and recorded via phone or interview every 4 weeks.Every follow-up retention rate of every drug group equals current patient number continuing therapy/initial patient number of this drug group

  4. Trends in the use of antiepileptic drugs (AEDs) among pregnant women in the U.S., 2001-2007: a Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) study

    Science.gov (United States)

    Bobo, William V.; Davis, Robert L.; Toh, Sengwee D.; Li, De-Kun; Andrade, Susan E.; Cheetham, T. Craig; Pawloski, Pamala; Dublin, Sascha; Pinheiro, Simone; Hammad, Tarek; Scott, Pamela E.; Epstein, Richard A.; Arbogast, Patrick G.; Morrow, James A.; Dudley, Judith A.; Lawrence, Jean M.; Avalos, Lyndsay A.; Cooper, William O.

    2012-01-01

    Background Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the U.S., 2001-2007. Methods We analyzed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified live-born deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (N = 585,615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Results Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1,000 deliveries) and 2007 (21.9 per 1,000 deliveries), driven primarily by a five-fold increase in the use of newer AEDs. Thirteen percent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. Conclusions AED use during pregnancy increased between 2001 and 2007, driven by a five-fold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed. PMID:23061694

  5. Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study

    Directory of Open Access Journals (Sweden)

    Priya Marimuthu

    2016-01-01

    Full Text Available Objectives: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs. Methods: We did a randomized, double-blind, placebo-controlled parallel group trial, in SRM Medical College Hospital and Research Centre, Kattankulathur, Kancheepuram, Tamil Nadu, India between April 2013 and September 2013. Fifty-nine epileptic patients taking AEDs with subjective memory complaints were recruited and randomized to either Group 1 to receive 16 weeks of once-daily memantine, (5 mg for first 8 weeks, followed by memantine 10 mg for next 8 weeks or Group 2 to receive once daily placebo. This trial is registered with Clinical Trial Registry of India CTRI/2013/04/003573. Results: Of 59 randomized patients, 55 patients completed the study (26 memantine and 29 placebo. Memantine group showed statistically significant improvement in total mini mental state examination score from baseline (P = 0.765 to 16 th week (P < 0.001 in comparison with the placebo. The Weshler′s Memory Scale total score in memantine group improved significantly after 8 weeks (P = 0.002 compared with baseline (P = 0.873 and highly significant at the end of 16 th week (P < 0.001. The self-rated quality of life and memory in memantine group also significantly improved at the study end. Conclusion: We conclude that once-daily memantine (10 mg treatment significantly improved cognition, memory and quality of life in epileptic patients with mild to moderate cognitive impairment and was found to have a favorable safety profile.

  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. CLINICAL USE OF ANTIEPILEPTIC DRUGS IN THE MANAGEMENT OF CHRONIC PAIN%抗癫痫药物治疗神经病理性疼痛的对照研究

    Institute of Scientific and Technical Information of China (English)

    赵序利; 许永广; 宋文阁; 傅志俭

    2012-01-01

    目的:回顾性分析卡马西平和加巴喷丁治疗原发性三叉神经痛、带状疱疹以及带状疱疹后遗神经痛的疗效、安全性和不良反应.方法:102位患者进入本研究,比较卡马西平或加巴喷丁治疗前后患者疼痛强度的改变和对睡眠影响的改善;依据药物分类,比较两种药物的副作用和不良反应.结果:卡马西平治疗原发性三叉神经痛起效较加巴喷丁快,二者长期疗效相当;加巴喷丁治疗带状疱疹和带状疱疹后神经痛的疗效优于卡马西平;疗效随治疗时间的延长而增加.卡马西平的副作用和不良反应事件发生率较加巴喷丁高.结论:抗癫痫药物卡马西平和加巴喷丁是治疗神经病理性疼痛的有效药物,可以改善患者的睡眠,但副作用和不良反应发生率高.%Objective: To evaluate the effects, safety and adverse effects of carbamazepine and gabapentin in the treatment of primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia. Methods: A total of 102 patients who suffered from primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia were assessed with changes in pain and sleep interference improvement after treatment with carbamazepine or gabapentin. The adverse events were evaluated and calculated between the carbamazepine and gabapentin. Results: Both carbamazepine and gabapentin had the same long term effects on trigeminal neuralgia, but carbamazepine got a rapid analgesia and sleep improvement effect than gabapentin. Gabapentin was more effective than carbamazepine in controlling pain and in improving sleep interference caused by herpes zoster and postherpetic neuralgia. The therapeutic effects was continually improved over time. Carbamazepine caused more adverse events than gabapentin. Conclusion: Antiepileptic drugs were effective in controlling neuropathic pain, and improved patient's sleep interference caused by pain. But they had a high risk in causing

  8. 16 CFR 1025.36 - Motions to compel discovery.

    Science.gov (United States)

    2010-01-01

    ... ADJUDICATIVE PROCEEDINGS Discovery, Compulsory Process § 1025.36 Motions to compel discovery. If a party fails... examination to the extent possible with respect to other areas of inquiry before moving to compel discovery....

  9. Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Georg Anton Giæver Beiske

    2015-01-01

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

  10. Drug: D07583 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07583 Mixture, Drug Phenytoin - phenobarbital mixt; Aleviatin with phenobarbital (TN) Phenytoin...ystem and sensory organs 11 Agents affecting central nervous system 113 Antiepileptics 1139 Others D07583 Phenytoin...TEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB52 Phenytoin..., combinations D07583 Phenytoin - phenobarbital mixt PubChem: 96024446 ...

  11. 湖北省某院2010-2013年抗癫痫药物的临床利用分析%Clinical Application of Antiepileptic Drugs in A Hospital in Hubei From 2010 to 2013

    Institute of Scientific and Technical Information of China (English)

    兰鸿; 陈鸿梅; 李炯

    2015-01-01

    目的:了解湖北省某院抗癫痫药物( AEDs)的利用情况及发展趋势。方法对2010—2013年十堰市太和医院AEDs的用药品种、销售金额、用药频度( DDDs)、日均费用( DDC)、年均增长率( AARG)及排序比值( RM)进行统计分析。结果该院传统AEDs有6个品种,分别为苯妥英钠、卡马西平、丙戊酸钠、苯巴比妥,其中丙戊酸钠有国产的普通片剂和国内外合资的缓释片剂,卡马西平有国产的普通片剂和国内外合资的片剂;新型AEDs有5个品种,分别为左乙拉西坦、拉莫三嗪、奥卡西平、托吡酯和加巴喷丁。2010—2013年AEDs的销售金额和DDDs逐年增长,AARG为13.85%,丙戊酸钠缓释片、丙戊酸钠和奥卡西平4年中 DDDs 排序始终保持在前3位;新型AEDs的DDC(16.93~36.28)明显高于传统AEDs(0.38~5.22),且RM均大于1。结论经济因素影响着AEDs的选择,该院AEDs仍以传统AEDs为主,需大力发展新型AEDs的自主研发,切实降低药价,造福广大患者。%Objective To investigate the application status and development trend of antiepileptic drugs( AEDs)in a hospital in Hubei. Methods Statistical analyses were conducted on the 2010—2013 data of AEDs in Taihe Hospital in Shiyan. The data included drug varieties,sales amount,defined daily doses( DDDs),defined daily cost( DDC),annual average rate of growth(AARG)and sorting ratio(RM). Results There were 6 major varieties of traditional AEDs,including dilantin, carbamazepine, sodium valproate and phenobarbital. The sodium valproate had two subcategories, the common homemade tablets and controlled-release tablets jointly made by home and abroad companies. The carbamazepine also had two subcategories,the common homemade tablets and tablets jointly made by home and abroad companies. New AEDs had 5 varieties including levetiracetam,lamotrigine,oxcarbazepine,topiramate and gabapentin. Between 2010 and 2013,the sales

  12. 常用新型抗癫痫药物对癫痫患儿认知功能的影响%Effects of commonly used new antiepileptic drugs on cognitive function in children with epilepsy

    Institute of Scientific and Technical Information of China (English)

    石景鹤; 王家勤; 陈国洪

    2014-01-01

    in some ways.Antiepileptic drugs through the neurotransmitter ,ion channels,the second messenger ,and other links to adjust control seizures .Thus reduce cognitive impairment of epilepsy , improve the quality of life of patients ,but also affect children′s cognitive function in some ways .

  13. 37 CFR 41.156 - Compelling testimony and production.

    Science.gov (United States)

    2010-07-01

    ... must: (1) In the case of testimony, identify the witness by name or title, and (2) In the case of a... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Compelling testimony and... Cases § 41.156 Compelling testimony and production. (a) Authorization required. A party seeking...

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

    OpenAIRE

    M Vijey Aanandhi; Debojit Bhattacherjee; Anirban Ray; P Samuel Gideon George

    2015-01-01

    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 vari...

  15. ABCB1基因位点(C3435T)多态性与癫痫耐药关联性的Meta分析%Meta analysis of relationship between polymorphism of gene site (C3435T) of ABCB1 and antiepileptic drug resistant

    Institute of Scientific and Technical Information of China (English)

    彭锐; 张洪; 张英; 魏丹芸

    2015-01-01

    目的:探讨ABCB1的基因位点(C3435T)多态性与癫痫耐药关联性。方法计算机检索Pubmed、Science direct、Wiley online library、Web of Science、中国知网、万方数据库和维普中文科技期刊数据库,纳入抗癫痫药耐药与抗癫痫药敏感的随机对照试验,同时查阅检索结果中所附相似文献及参考文献,检索文献均为建库至2014年6月15日。由两名评价员单独进行文献筛选及资料提取,采用RevMan 5.0软件进行Meta分析及其他统计学分析。结果共纳入文献10篇,癫痫患者中耐药815例,敏感976例。Meta分析结果显示,C3435T位点多态性在等位基因模型、显性模型、隐性模型、共显性模型(CC/TT组)下整体效应差异有统计学意义(P0.05);而印度地区ABCB1 C3435T位点基因多态性与癫痫耐药在等位基因模型和隐性基因模型下整体效应差异有统计学意义(P0.05). In the allele gene model, OR=0.70, 95%CI (0.54, 0.93);recessive gene model, OR=0.72, 95%CI (0.49, 1.07). Conclusion ABCB1 C3435T loci polymor-phism dose not relate to the antiepileptic drug resistant among Chinese; but ABCB1 C3435T loci polymorphism relates to the antiepileptic drug resistant among Indian.

  16. 非卡马西平所致药疹与 HLA -B*1502基因型相关性研究%Study on the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502

    Institute of Scientific and Technical Information of China (English)

    武美艳; 侯春风; 李军; 李保敏

    2015-01-01

    Objective To discuss the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502. Methods The genotype of HLA -B*1502 of patients, including 26 cases of drug eruptions caused by non -carbamaz-epine antiepileptics and 8 cases caused by carbamazepine , were detected in peripheral blood by the PCR -SS0 probe.Results There were 26 patients in the group of non -carbamazepine administration .The expres-sion of HLA-B*1502 gene was positive in 1 case and negative in 14 ca-ses in the group of oxcarbazepine administration;the expression was neg-ative in all the 3 cases in the group of lamotrigine administration , the ex-pression was negative in all the 3 cases in the group of levetiracetam ad-ministration , the expression was negative in both of the 2 cases in the group of phenytoinum administration , the expression was negative in both the 2 cases in the group of phenobarbital administration , and the expres-sion was negative in 1 cases in the group of valproate administration . There were 8 patients in the group of carbamazepine administration .The expression of HLA-B*1502 gene was positive in 5 cases and negative in 3 cases.Patients with drug eruption caused by antiepileptic drugs all changed the administration .The result showed that the positive expression rate of HLA-B*1502 gene was lower in the group of non-carbamazepine administration than that in the group of carbamazepine administration ( P<0.05 ).Con-clusion There was no correlation between the drug eruption caused by non -carbamazepine administration and the genotype of HLA-B*1502.Carbamazepine can be switched , if necessary , in cases who have drug eruption caused by administration of non -carbamazepine antiepileptics .%目的:评价非卡马西平抗癫痫药所致药疹与HLA-B*1502基因型的相关性。方法用PCR-SS0探针法测定26例非卡马西平抗癫痫药物药疹的患者及8例用卡马西平药疹的患者外周血白细胞HLA-B*1502

  17. Antiepileptic Potential of Matrine via Regulation the Levels of Gamma-Aminobutyric Acid and Glutamic Acid in the Brain

    Directory of Open Access Journals (Sweden)

    Jun Xiang

    2013-12-01

    Full Text Available Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp, gamma-aminobutyric acid (GABA, glutamic acid (Glu, glycine (Gly in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  18. Antiepileptic potential of matrine via regulation the levels of gamma-aminobutyric acid and glutamic acid in the brain.

    Science.gov (United States)

    Xiang, Jun; Jiang, Yugang

    2013-12-05

    Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  19. Drug: D03844 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03844 Mixture, Drug Phenytoin - phenobarbital - caffeine and sodium benzoate; Hydantol F (TN) Phenytoin...3 Antiepileptics 1139 Others D03844 Phenytoin - phenobarbital - caffeine and sodium benzoate Anatomical Ther...PTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB52 Phenytoin, combinations D03844 Phenytoin - phenobarbital - caffeine and sodium benzoate PubChem: 17397930 ...

  20. Correlation analysis between epilepsy and anti-epileptic drugs and bone mineral density of patients with epilepsy%癫痫病及抗癫痫药物对癫痫患者骨密度影响的相关性分析

    Institute of Scientific and Technical Information of China (English)

    郭华爱; 毓青; 王凤楼; 杨卫东; 陈英; 陈旨娟; 杨二娟

    2013-01-01

    Objective: To investigate the effects of epilepsy and anti-epileptic drugs(AEDs) on bone mineral density(BMD) of patients with epilepsy. Methods: 160 cases aged between 20 and 60 years old were selected as subjects. All of them had the disease for more than nine months and had been taking AEDs for more than six months. All were free of other diseases and none was taking any medication that might interfere with bone metabolism other than AEDs. BMDs at the right heel were measured with the ultrasonic BMD instrument. Detailed clinical information of each patient were obtained by the researcher. All of the related risk factors in the data were stratified according to certain degree. Fifty normal controls were involved. Then single factor chi-square test and multivariate logistic regression analysis were analyzed. Results: There was statistically significant difference between epileptics and normal group in BMD (P0.05). Multivariate logistic regression analysis identified GTCS,polytherapy and the duration of anticonvulsant therapy were as the related and independent risk factors(OR value, 1.105, 5.710, 5.820, respectively; P<0.05). Conclusion: The results indicate that both epilepsy and anti-epileptic drugs can lead to the change of BMD of patients with epilepsy, and GTCS, polytherapy and the duration of anticonvulsant therapy are important risk factors of low BMD. It can be used as valuable reference to prevent bone mass loss and fractures of epileptic patients effectively.%目的:研究癫痫病本身及抗癫痫药物(AEDs)与癫痫患者骨密度(BMD)异常的相关性.方法:采用超声法对160例年龄在20~60岁、病程≥9个月、AEDs治疗时间≥6个月的癫痫患者进行BMD检测,收集相关的临床资料并设置正常对照组50例.根据癫痫的病程、发作类型、服用AEDs的数量及种类、治疗时间分组,分析各组临床指标与骨量异常的相关性.结果:癫痫患者组BMD异常率与正常对照组比较有显著差

  1. Effect on Intelligence in Children with Epilepsy and Adaptabli ty Analysis and Antiepileptic Drug Treatm ent%癫痫儿童智能和适应能力分析及抗癫痫药物治疗的影响

    Institute of Scientific and Technical Information of China (English)

    黄彦思; 林云宾; 冯婉萍; 曾丽韫; 朱国辉; 张美胡

    2015-01-01

    目的:分析癫痫儿童与正常儿童智能和适应能力差别,观察抗癫痫药物治疗前后对智能和适应能力的影响。方法:选择2013年1月至2013年12月我院50例9~16岁癫痫患儿,随机分为两组,分别给予奥卡西平( OXC)和卡马西平( CBZ)治疗,于治疗前和治疗12个月后测试智能和适应能力,并选择同期性别、年龄、父母文化程度与之相匹配的健康检查正常儿童50例设为正常组,采用相同的方法测试智能和适应能力。结果:癫痫组和正常组WISC-R评分中语言IQ、操作IQ及总IQ评分差异无显著性( P>0.05);单项评分中,算术、常识、理解、图片排列、类同、拼图评分差异无显著性( P>0.05);但癫痫儿童背数、译码、填缺评分明显低于正常组(P<0.05)。癫痫组患儿P300潜伏期异常率为28.0%,高于正常组,SLPS正常率为70.0%,低于正常组( P<0.05)。服用抗癫痫药物12个月,CBZ组患儿背数评分较治疗前略有降低,两组语言IQ、操作IQ、总IQ评分及各单项评分较治疗前均略有上升,差异均无显著性( P>0.05);治疗前后两组患儿适应能力比较差异无显著性( P>0.05)。结论:智力正常的癫痫患儿伴有不同程度的适应能力和智能低下,常规抗癫痫药物及新型抗癫痫药物均对智能和适应能力无明显影响,癫痫患儿一旦确诊及时治疗避免疾病造成更严重的智能损害。%Objective:To analyze the difference of intelligence of epileptic children and normal children and the ability to adapt, observe the intelligence and ability to adapt to the effect before and after treatment with antiepileptic drugs.Method: 50 cases of 9~16 years old children with epilepsy in our hospital from January 2013 to December 2013, were randomly divided into two groups, respectively given oxcarbazepine ( OXC) and C Masi Bing ( CBZ) treatment

  2. Drug hypersensitivity syndrome

    OpenAIRE

    Rashmi Kumari; Dependra K Timshina; Devinder Mohan Thappa

    2011-01-01

    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 abnormalit...

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

    Directory of Open Access Journals (Sweden)

    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

  4. 抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响%Influence of Antiepileptic Drugs Magnesium Valproate Sustained Release Tablets on Female Reproductive Endocrine

    Institute of Scientific and Technical Information of China (English)

    张冬梅; 孙凤英

    2015-01-01

    目的:分析抗癫痫药丙戊酸镁缓释片对女性癫痫患者生殖内分泌的影响。方法选取2010年3月—2013年3月滨州医学院附属医院收治的50例女性癫痫患者,均给予丙戊酸镁缓释片口服治疗,0.5 g/ d。分别于患者用药前及用药3、6个月时,抽取空腹静脉血,采用酶联免疫吸附试验检测卵泡刺激素( FSH)、黄体生成素(LH)、催乳素(PRL)、雌二醇(E2)、孕酮(P)、睾酮(T)水平。同时观察患者月经及卵巢变化情况,多囊卵巢综合征(PCOS)、高雄激素血症发生情况。结果50例患者用药前及用药3、6个月时,FSH、LH、PRL、E2、P、T 比较,差异均有统计学意义( P <0.05);其中用药3、6个月时 FSH、T 均高于用药前,PRL、E2、P 均低于用药前( P <0.05)。用药6个月后,38例(76.0%)患者月经周期尚在参考范围内;12例(24.0%)患者月经周期出现异常。6例(12.0%)患者出现 PCOS。16例(32.0%)患者为高雄激素血症。结论丙戊酸镁缓释片可使女性癫痫患者机体PRL、P 水平降低,T 水平提高。%Objective To investigate the impact of magnesium valproate sustained release tablets on female reproductive endocrine and to explore the rational use of anti - epileptic drugs. Methods A total of 50 female patients with epilepsy who were admitted into the Affiliated Hospital of Binzhou Medical University from March 2010 to March 2013 were enrolled. The subjects were treated with magnesium valproate sustained release tablets with 0. 5 g/ d. Before the intervention and three months and six months after the intervention began,the limosis vein blood of the subjects was sampled. Then the enzyme linked immunosorbent assay( ELISA) was employed to test the level of follicle stimulating hormone ( FSH),luteinizing hormone(LH),prolactin( PRL),estradiol( E2 ),progesterone( P) and testosterone( T). The changes of menstruation and ovary

  5. Drug: D05775 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05775 Drug Rufinamide (JAN/USAN/INN); Banzel (TN) C10H8F2N4O 238.0666 238.1935 D05...03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AF Carboxamide derivatives N03AF03 Rufinamide D05775 Rufinamide (JAN/USAN/INN) USP dru... Therapeutic category of drugs in Japan [BR:br08301] 1 Agents affecting nervous system and sensory organs 11... Agents affecting central nervous system 113 Antiepileptics 1139 Others D05775 Ru...g classification [BR:br08302] Anticonvulsants Sodium Channel Agents Ru

  6. Drug: D08964 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08964 Drug Perampanel (USAN); Fycompa (TN) C23H15N3O 349.1215 349.3847 D08964.gif ...ATC) classification [BR:br08303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AX Other antiepileptics N03AX22 Perampane...l D08964 Perampanel (USAN) USP drug classification [BR:br08302] Anticonvulsants Glu...tamate Reducing Agents Perampanel D08964 Perampanel (USAN) Target-based classific...PA receptor [HSA:2890 2891 2892 2893] [KO:K05197 K05198 K05199 K05200] Perampanel [ATC:N03AX22] D08964 Perampanel

  7. Drug: D02103 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02103 Drug Phenytoin sodium for injection (JP16); Phenytoin sodium (USP); Aleviati...egory: 1132 ATC code: N03AB02 Hydantoins There is a strong association between the risk of developing SJS/TEN with Phenytoin... central nervous system 113 Antiepileptics 1132 Hydantoins D02103 Phenytoin sodiu...303] N NERVOUS SYSTEM N03 ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AB Hydantoin derivatives N03AB02 Phenytoin D02103 Phenytoin... sodium for injection (JP16); Phenytoin sodium (USP) USP drug clas

  8. Drug: D00280 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00280 Drug Clonazepam (JP16/USP/INN); Klonopin (TN) C15H10ClN3O3 315.0411 315.7112...gents affecting central nervous system 113 Antiepileptics 1139 Others D00280 Clonazepam (JP16/USP/INN) Anato... ANTIEPILEPTICS N03A ANTIEPILEPTICS N03AE Benzodiazepine derivatives N03AE01 Clonazepam D00280 Clonazepam (J...P16/USP/INN) USP drug classification [BR:br08302] Anticonvulsants Gamma-aminobutyric Acid (GABA) Augmenting Agents Clonazepam... D00280 Clonazepam (JP16/USP/INN) Anxiolytics Benzodiazepines Clonazepam D00280 Clonazepam

  9. 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.

  10. 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.

  11. 高效液相色谱法同时测定四种抗癫痫药物的血药浓度%Simultaneous determination of the plasma concentration in four antiepileptic drugs using high performance liquid chromato-graphy

    Institute of Scientific and Technical Information of China (English)

    盛高峰; 詹少卿

    2015-01-01

    目的:建立用HPLC同时测定血清中多种抗癫痫药物卡马西平( carbamazepine,CBZ)、苯巴比妥( phenobarbital, PB)、硝西泮( nitrazepam,NTZ)、氯硝西泮( clonazepam,CNZ)等的方法。方法用一定方法处理血清样本,色谱柱为Nova-pak C18柱(150 mm ×3.9 mm,4μm);流动相为0.01 mol/L磷酸二氢钾缓冲液(pH 2.15)-乙腈(29∶71,V/V),监测波长223 nm;流速1 ml/min,柱温30℃。结果样品血清经处理,所留杂质不干扰被检测药品。在该色谱条件下以上药物能良好分离,在0.01-10 mg/L范围浓度与峰面积呈良好的线性关系(r>0.9990),方法回收率均大于90%,日内、日间RSD均小于10%。结论该方法快速、准确、简便、实用,适用于以上治疗药物的治疗监测。%Objective To establish a method for simultaneously determining the plasma concentration in multiple antiepileptic drugs, such as carbamazepine( CBZ) ,phenobarbital( PB) ,nitrazepam( NTZ) and clonazepam( CNZ) using high performance liquid chromatog-raphy( HPLC) . Methods The serum samples were processed by a certain method,in which the chromatographic column was Nova-pak C18(150 mm ×3.9 mm, 4 μm),the mobile phase was composed of 0. 01 mol/L monopotassium phosphate buffer solution(pH 2. 15)and acetonitrile(29∶71),the monitoring wavelength was 223 nm at a flow rate of 1 ml/min, and the column temperature was set at 30 ℃. Results The residual impurities of the processed serum did not interfere with the tested drugs,which were well separated under the chromatographic conditions. The concentration had a stable linear relationship with the peak area in the range of 0. 01-10 mg/L(r>0. 999 0). Of all the drugs,recoveries of the method were all higher than 90% while the relative standard deviations(RSD)of within-day and between-day were both less than 10%. Conclusion This method was efficient,accurate,simple and practical,and could be applicable for therapeutic drug monitoring.

  12. [Epilepsy and cognition: the role of antiepileptic drugs].

    Science.gov (United States)

    García-Peñas, Juan José; Fournier-Del Castillo, M Concepción; Domínguez-Carral, Jana

    2014-02-24

    Introduccion. Multiples y muy diversos factores se relacionan con la alteracion cognitiva en la epilepsia, incluyendo el efecto adverso directo de los farmacos antiepilepticos (FAE). El uso de los FAE requiere de un riguroso equilibrio entre riesgo y beneficio para conseguir asi el mejor control de las crisis con el menor numero de efectos adversos neurocognitivos. Objetivo. Analizar los efectos adversos cognitivos generales y especificos de los FAE de primera, segunda y tercera generacion. Desarrollo. Todos los FAE disponibles pueden producir efectos adversos cognitivos, que son mas frecuentes en politerapia, con dosis totales altas y niveles sericos elevados. Las alteraciones mas comunes son el descenso de la capacidad de reaccion y de la velocidad de procesamiento con afectacion concomitante de la memoria, la atencion y el lenguaje. Sin embargo, hay gran controversia sobre la existencia o no de perfiles cognitivos especificos para cada uno de los distintos FAE y se dispone de una informacion contradictoria al respecto por la inadecuada metodologia de los estudios comparativos. Conclusiones. Los efectos adversos cognitivos de los FAE son frecuentes y pueden afectar negativamente la tolerabilidad, el cumplimiento y el mantenimiento a largo plazo del tratamiento antiepileptico. Se debe considerar el potencial efecto adverso cognitivo de los distintos FAE a la hora de elegir un tratamiento y es importante reconocer e identificar precozmente estos efectos adversos y saber como pueden afectar a los pacientes.

  13. Antiepileptic drug prescribing before, during and after pregnancy

    DEFF Research Database (Denmark)

    Charlton, Rachel; Garne, Ester; Wang, Hao;

    2015-01-01

    and after pregnancy were identified in each of the databases. AED prescribing patterns were analysed, and the choice of AEDs and co-prescribing of folic acid were evaluated. Results In total, 978 957 women with 1 248 713 deliveries were identified. In all regions, AED prescribing declined during pregnancy...... co-prescribed with high-dose folic acid: ranging from 1.0% (CI950.3–1.8%) in Emilia Romagna to 33.5% (CI9528.7–38.4%) in Wales. Conclusion The country's differences in prescribing patterns may suggest different use, knowledge or interpretation of the scientific evidence base. The low co......-prescribing of folic acid indicates that more needs to be done to better inform clinicians and women of childbearing age taking AEDs about the need to offer and receive complete preconception care....

  14. 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...... investigated possible differences in suicide risk associated with different AEDs. Methods The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own...... control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-nave patients. Results There were 6780 cases committing suicide in the 10-year study period, of which 422 received AED treatment at the time of suicide...

  15. The Effectiveness of Mood Stabilizers and Antiepileptic Medication for the Management of Behaviour Problems in Adults with Intellectual Disability: A Systematic Review

    Science.gov (United States)

    Deb, S.; Chaplin, R.; Sohanpal, S.; Unwin, G.; Soni, R.; Lenotre, L.

    2008-01-01

    Background: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. Method: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood…

  16. 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

  17. Repair of abnormal perfusion foci in idiopathic epilepsy patients under long-term antiepileptic treatment

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Siyu Zhao; Yaqing Liu

    2011-01-01

    Epileptic seizure control and the disappearance of epileptiform discharge are not indicative of the absence of abnormal perfusion foci.Perfusion abnormalities are a major cause of epileptic discharge, and the existence of abnormal perfusion foci implies possible relapse.Very little is known about perfusion abnormality repair in epilepsy.The present study selected 43 cases of idiopathic epilepsy under antiepileptic drug control for an average of 24 months.Comparisons between interictal single-photon emission CT (SPECT)images and long-term electroencephalogram (EEG) pre- and post-treatment showed that cases of normal SPECT increased by 48% (12/25) following treatment, with a total number of 15 reduced foci (36%, 15/41).Perfusion foci, i.e., region of interest, were altered following treatment.These changes included:normal to abnormal in 3 cases (7%, 3/43; 2 hyperperfusion and 1 hypoperfusion); abnormal to normal in 14 cases (32%, 14/43; 10 pre-treatment hypoperfusion and 4 hyperperfusion); abnormal to abnormal in 7 cases (16%, 7/43; hyperperfusion to hypoperfusion in 5 cases, hypoperfusion to hyperperfusion in 2 cases).Long-term EEG revealed in an increase in the number of normal cases by 20 (40%, 20/39), and there were 25 fewer cases with epileptiform discharges (66%, 25/38).These findings demonstrate that long-term control of anti-epileptic drugs partially repaired cerebral perfusion abnormalities and reduced epileptiform discharges in idiopathic epilepsy.

  18. Kinetics of drug interactions in the treatment of epilepsy.

    Science.gov (United States)

    van der Kleijn, E; Vree, T; Guelen, P; Schobten, F; Westenberg, H; Knop, H

    1978-10-01

    The interactions of antiepileptic drugs in multiple drug treatment have been discussed. Although some combinations may lead to predictable increase or decrease of clearance of the respective drugs, most combinations will individually lead to a reduced predictability. Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen. Also physiological conditions control the individual clearance of antiepileptic drugs. PMID:700910

  19. 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

  20. Role of piracetam on cognitive function in epilepsy and with antiepileptics in rats

    Directory of Open Access Journals (Sweden)

    Siddharth R. Chaudhari

    2013-10-01

    Full Text Available Background: To study extent of cognitive impairment by epilepsy & antiepileptic treatment and evaluate the role of piracetam on it. Methods: 48 animals were divided into 6 groups: I-Control, II- Topiramate, III-Topiramate+Piracetam, IV-Valproate, V-Valproate+Piracetam, VI-Piracetam. Baseline cognitive functions were measured using Cook’s pole climbing apparatus (CPCA and Elevated plus maze (EPM. In CPCA, on completion of training, number of avoidances (NOA out of 10 trials were noted while in EPM, transfer latency (TL was measured. Kindling was induced by 30mg/kg Pentylenetetrazol (PTZ, i.p. to all groups (except Group I on alternate days till seizures developed. Groups were treated with respective drugs orally for 21 days and cognitive functions measured again. Results: Significant decrease in NOA & increase in TL was observed after PTZ kindling. Topiramate further significantly impaired NOA and TL whereas Valproate significantly reduced NOA in CPCA but increase in TL was not significant. Treatment with Piracetam significantly increased Topiramate, Valproate and PTZ kindling induced decrease in NOA as also significantly reduced Topiramate and PTZ kindling induced increase in TL. Conclusion: Seizures are associated with cognitive impairment. Cognitive impairment caused by Sodium valproate differs from Topiramate. Piracetam, a known nootropic can be used in alleviating cognitive impairment associated with epilepsy & chronic antiepileptic therapy. [Int J Basic Clin Pharmacol 2013; 2(5.000: 634-639

  1. 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...... in smoking cessation. On-going research is examining the potential effects of nicotine vaccination as relapse prevention.......OBJECTIVES: To provide a short review of the evidence base supporting smoking cessation interventions, including behavioral therapy and pharmacological treatment options. METHODS: Published meta-analysis was mainly used supplemented with a limited literature search. RESULTS: Effective smoking...

  2. 12 CFR 261.23 - Subpoenas, orders compelling production, and other process.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Subpoenas, orders compelling production, and other process. 261.23 Section 261.23 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF... Agencies, and Others in Certain Circumstances § 261.23 Subpoenas, orders compelling production, and...

  3. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    Science.gov (United States)

    Krasowski, Matthew D.

    2010-01-01

    In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy. PMID:20640233

  4. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    Directory of Open Access Journals (Sweden)

    Matthew D. Krasowski

    2010-06-01

    Full Text Available In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

  5. Results of work of antiepileptic service in samara region

    Directory of Open Access Journals (Sweden)

    Kordonskaya I.S.

    2012-06-01

    Full Text Available

    The goal of the research is the analysis of work of adult antiepileptic service over the period of ten years. Individual cards of 9634 patients treated by the epileptologist were studied. More than a half of patients were no older 30 years. Focal epilepsy prevailed in all age groups. Treatment in a mode of monotherapy was received by 65,9 % of patients.Frequency of remission of epilepsy considerably increased after treatment correction by epileptologist. Pregnancy did not worsen the course of epilepsy at adequate monitoring of treatment.

  6. Varied effects of conventional antiepileptics on responding maintained by negative versus positive reinforcement.

    Science.gov (United States)

    Roberts, Celeste; Harvey, Mark T; May, Michael E; Valdovinos, Maria G; Patterson, Tina G; Couppis, Maria H; Kennedy, Craig H

    2008-02-27

    We analyzed the effects of four conventional antiepileptic drugs (AEDs) - carbamazepine (CBZ), ethosuximide (ETH), phenytoin (PHT), and valproate (VPA) - on operant behavior maintained by negative or positive reinforcement contingencies. Rats were trained to lever press on a free-operant avoidance schedule or variable-interval (VI) schedule of appetitive reinforcement. Dose-effect functions were separately established on each reinforcement contingency for CBZ (12.5-100 mg/kg), ETH (25-200 mg/kg), PHT (12.5-50 mg/kg), and VPA (50-400 mg/kg). CBZ and PHT reduced responding on free-operant avoidance and VI appetitive reinforcement tasks, with positively reinforced behavior reduced at lower drug dosages than negatively reinforced responding. ETH and VPA reduced responding on the VI appetitive reinforcement task, but did not alter behavior maintained on the free-operant avoidance schedule. Our results suggest that conventional AEDs vary in their effect on operant behavior, depending on the type of reinforcement process maintaining responding.

  7. The opportunities & limits of compellence strategies : the quest for a framework for analysis

    NARCIS (Netherlands)

    Angeren, Joannes Franciscus Wilhelmus van

    2006-01-01

    This thesis concerns coercive strategies, in particular ‘compellence’, the counterpart of the better-known notion ‘deterrence’, both holding a special position in the contemporary International Relations theory. Compellence is defined as, “the use of threatened force — and at times the actual use of

  8. Diversity Is a Compelling Interest, and Affirmative Action Is an Important Strategy for Achieving It

    Science.gov (United States)

    Vasquez, Melba J. T.; Jones, James M.

    2007-01-01

    Responds to comments made by Pipes and Kuncel and Sackett on the current authors' original article (see record 2006-01690-003). The current authors respond to the various points raised in the commenting articles, and suggest that diversity is a compelling interest and affirmative action is one means of achieving it. They stand by their original…

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

    NARCIS (Netherlands)

    E. Peeren

    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. Signific

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

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Carstensen, Lisbeth; Wohlfahrt, Jan;

    2014-01-01

    and untreated individuals. Associations were expressed as incidence rate ratios (IRRs) estimated using Poisson regression. Among persons without epilepsy, use of anti-epileptic medication increased the rates of most cancers little or not at all, although we observed moderately increased rates of liver, mouth...... and throat, and respiratory tract cancers (IRRs 1.40-1.59). In contrast, we observed strong associations between epilepsy and the rates of central nervous system and mouth and throat cancers (IRRs 2.00-3.91), and a modest association between epilepsy and the rate of respiratory tract cancers (IRRs 1...... that are responsible for the increased cancer risk among epileptics but another aspect of epilepsy diagnosis or treatment or an etiologic factor common to the two conditions....

  11. The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After First Attack: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Farhad ASSARZADEGAN

    2015-06-01

    Full Text Available 1024x768 1024x768 Normal 0 false false false EN-US X-NONE AR-SA /* 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-qformat:yes; 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:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} How to Cite This Article: Assarzadegan F, Tabesh H, Hesami O, Derakhshanfar H, Beladi Moghadam N, Shoghli A, Beale A.D, Hosseini-Zijoud S.M. The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After First Attack: A Randomized Clinical Trial. Iran JChild Neurol. Spring 2015; 9(2:46-52.AbstractObjectiveEpilepsy is a serious, potentially life-shortening brain disorder that occurs in patients of all ages and races. A total of 2–4% of people have experienced seizures at least once in their lifetime. Although treatment usually begins after a seizure, it is an important question whether the first cases of seizure do need to be treated by antiepileptic drugs. In this manner, we compare the recurrence rates of epilepsy in first seizure patients treated with sodium valproic acid as an antiepileptic drug versus a placebo.Material & MethodsIn a randomized clinical trial study, 101 first seizure patients were randomly divided into two groups: one group was treated with antiepileptic drugs (sodium valproate 200mg, three times a day and the other group was given a placebo.The recurrence rate of seizures was evaluated and compared between the groups after 6 months of follow up.ResultsEight recurrence cases were detected. All

  12. Effect of anti-epileptic, nootropic drugs on the expression of ERK2 and NCAM1 in the hippocampus changes on the epileptic rats with cognitive dysfunction%抗痫促智药物对认知功能障碍致痫大鼠海马细胞外信号调节激酶2及神经细胞黏附分子1表达的影响

    Institute of Scientific and Technical Information of China (English)

    孔庆霞; 梁汝庆; 高建英; 孙冉; 李雷; 褚旭; 夏敏

    2013-01-01

    目的 探讨细胞外信号调节激酶2(ERK2)及神经细胞黏附分子1(NCAM1)在癫痫认知功能障碍中的作用及抗痫、促智药物对二者作用.方法 将120只Wistar大鼠分为对照组、致痫组和卡马西平组、奥卡西平组、茴拉西坦组、盐酸多奈哌齐组治疗30 d,对照组用生理盐水造模,其余5组用匹罗卡品诱导癫痫模型,将造模成功的大鼠给予上述成药物干预模型,大鼠的学习记忆能力通过Morris水迷宫实验测试,记录逃避潜伏期和原平台象限游泳时间;并用RT-PCR法检测NCAM1、ERK2在大鼠海马组织中的mRNA表达,免疫组化法检测大鼠海马组织中NCAM1和ERK2的蛋白表达.结果 定位航行试验中,与对照组大鼠逃避潜伏期相比,致痫组[(67.14±7.37)s]>对照组[(35.78±4.84)s](P<0.01),其中卡马西平组与盐酸多奈哌齐组与致痫组比较,卡马西平组[(81.23±9.46)s]>致痫组[(67.14±7.37)s](P<0.01),盐酸多奈哌齐组[(53.75±6.74)s]<致痫组[(67.14±7.37)s](P<0.01).各组ERK2蛋白表达及mRNA比较为:卡马西平组<奥卡西平组<致痫组<茴拉西坦组<多奈哌齐组<对照组.与对照组比,多奈哌齐组>对照组(P<0.01),茴拉西坦组>对照组(P<0.05).结论 ERK2在癫痫发作30 d时在海马的表达水平下降,NCAM1则相反,ERK2活性的减低和NCAM1的过度表达可能是癫痫后认知功能损害的潜在机制.卡马西平能加重癫痫认知功能障碍程度,盐酸多奈哌齐可明显改善癫痫鼠的认知功能.%Objective To study the effect of anti-epileptic,nootropic drugs on the expression of NCAM and ERK2 in the hippocampus changes on the epileptic rats with cognitive dysfunction.Methods A total of 120Wistar rats were used.20 controls and 100 in which epilepticus with cognitive dysfunction were randomly assigned to 5 groups (n =20/group) that received daily treatments for 30 days with either (1) saline (epilepsy),(2) carbamazine (traditional anti-epileptic

  13. Does the Compelled Cooperation Determine the Structure of a Complex Network?

    Institute of Scientific and Technical Information of China (English)

    XUAN Qi; LI Yan-Jun; WU Tie-Jun

    2008-01-01

    Cooperation among individuals is considered to play an important role in the evolution of complex networked systems in physical,biological,economical and even epidemiological worlds,but its effects on the development of the systems is not so clear.We consider a specific kind of primal cooperation in a group of individuals,i.e.,an individual never cooperates with others except when compelled to do so.The lowest level of compelled cooperation,in which cooperators share no message or resources,is investigated in the background of complex networks driven by the simple game rock-paper-scissors.Simulation results show that with the evolution of the systems,the cooperation will spread all over the networks,and finally results in systems with modular structures and a scale-free property.

  14. Editor of COMPEL: The International Journal for Computation and Mathematics in Electrical and Electronic Engineering

    OpenAIRE

    Sykulski, J.K.

    2008-01-01

    COMPEL exists for the discussion and dissemination of computational and analytical methods in electrical and electronic engineering. The main emphasis of papers should be on methods and new techniques, or the application of existing techniques in a novel way. Whilst papers with immediate application to particular engineering problems are welcome, so too are papers that form a basis for further development in the area of study. A double-blind review process ensures the content's validity and r...

  15. Aperture maneuver with compelled breath (AMC) for moving tumors: A feasibility study with a moving phantom

    International Nuclear Information System (INIS)

    Respiration causes target motion, which is known to be one of the technical bottlenecks in radiotherapy, especially for stereotactic radio-surgery and intensity modulated radiotherapy (IMRT). To overcome this problem, aperture maneuver with compelled breath (AMC) has been developed. In order to simulate compelled respiratory motion, a moving phantom using a ventilator was designed. As the air flow was forced to the bellows, which simulates the lungs, by a ventilator, a film connected to the ventilator moved like the respiratory target motion. A software was developed to transfer multileaf collimator motion from breathless to actual periodic breathing conditions. Static fields as well as step-and-shoot IMRT fields were modified in accordance with moving shapes to follow the target position, using the software with the controlled breathing information. Film dosimetry for a small field and for IMRT fields with a moving phantom was performed. To evaluate clinical implementation, five healthy volunteers were tested to breathe through a ventilator, and all of them could adapt the compelled breath without any difficulties. Additive margins for a moving target with AMC were not larger than 3 mm for respiratory organ motions up to 18 mm, while those with the static beam were 9 mm. For IMRT fields, large discrepancies were present between a static target and a moving target with the static beam, while they coincided well with AMC. Clinical acceptable differences between the dose distributions from a static target with the static beam and from a moving target with AMC revealed that this technique could be applied clinically

  16. A retrospective two-center study of antiepileptic prophylaxis in patients with surgically treated high-grade gliomas

    Directory of Open Access Journals (Sweden)

    Diego Garbossa

    2013-01-01

    Full Text Available Background: The effectiveness of antiepileptic prophylaxis in patients with newly diagnosed high-grade glioma is debated. Craniotomy, surgical manipulation and bleeding are believed to favor the onset of seizures and, therefore, perioperative antiepileptic drugs (AEDs are generally used. Nevertheless, evidence to initiate preoperative AED prophylaxis are weak. Aim: Aim of this paper was to evaluate the need for AED prophylaxis in surgically-treated malignant glioma patients without history of seizures. Materials and Methods: We conducted a retrospective, two-center cohort study to assess the effectiveness of preoperative AED prophylaxis. Patients were divided in two groups: one with AED preoperative administration and the other without. Because of its non-hepatic metabolism, levetiracetam (LEV was chosen. Logistic regression models were used to investigate the odds ratio for each group. The explanatory variables included the treatment received, sex, age, and site of lesion. The outcome measure of successful LEV prophylaxis was seizure vs. no seizure post-operatively, at three and six months after surgery. Results: Our results showed that LEV prophylaxis was not a significant predictor of seizure occurrence, although the regression coefficient indicated a slight reduction in seizure risk following LEV administration. Patient′s age was a significant predictor of seizure occurrence. Younger patients had a higher risk of seizure in the six months post-surgery. Conclusions: We conclude that AEDs prophylaxis does not provide a substantial benefit to surgically treated high-grade glioma patients and should not be administered routinely. Further investigations are required to detect subgroups of patients at higher risk of developing seizures in order to selectively administer AED.

  17. 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.

  18. Native American Science Education: A Compelling Opportunity for the Integration of Earth and Space Science

    Science.gov (United States)

    Morrow, C. A.; Maryboy, N.; Begay, D.

    2005-05-01

    The strong relationships between Earth and sky in the worldviews of Native American people presents a wonderful opportunity for collaborations that can co-create compelling educational opportunities for both Native and non-Native learners. This paper will discuss the relationship among successful science education for Native Americans, standards-based science education, and informal science education. It will address some strategies for combining best practice in education with a deep cultural authenticity. Presenting astronomy in a culturally relevant and correct way is not only of value to the Native learner, but it is also of value to the non-Native learner because cultural relevance for Native people demands that science be presented via different learning modalities (e.g. visual, kinesthetic, tactile) and in a way that is more interconnected with other science and non-science disciplines. This kind of multi-modal and interdisciplinary approach is valuable and progressive for Non-native learners as well.

  19. Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population

    OpenAIRE

    Ritu Kumari; Ram Lakhan; Garg, R. K.; Kalita, J; Misra, U K; Balraj Mittal

    2011-01-01

    Background: In epilepsy, in spite of the best possible medications and treatment protocols, approximately one-third of the patients do not respond adequately to anti-epileptic drugs. Such interindividual variations in drug response are believed to result from genetic variations in candidate genes belonging to multiple pathways. Materials and Methods: In the present pharmacogenetic analysis, a total of 402 epilepsy patients were enrolled. Of them, 128 were diagnosed as multiple drug-resist...

  20. CONCEPT OF DRUG INTERACTION

    Directory of Open Access Journals (Sweden)

    Singh Nidhi

    2012-07-01

    Full Text Available 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 actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  1. 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.

  2. No compelling evidence of significant early star cluster disruption in the Large Magellanic Cloud

    CERN Document Server

    de Grijs, Richard; Anders, Peter

    2013-01-01

    Whether or not the rich star cluster population in the Large Magellanic Cloud (LMC) is affected by significant disruption during the first few x 10^8 yr of its evolution is an open question and the subject of significant current debate. Here, we revisit the problem, adopting a homogeneous data set of broad-band imaging observations. We base our analysis mainly on two sets of self-consistently determined LMC cluster ages and masses, one using standard modelling and one which takes into account the effects of stochasticity in the clusters' stellar mass functions. On their own, the results based on any of the three complementary analysis approaches applied here are merely indicative of the physical conditions governing the cluster population. However, the combination of our results from all three different diagnostics leaves little room for any conclusion other than that the optically selected LMC star cluster population exhibits no compelling evidence of significant disruption -- for clusters with masses, M_cl,...

  3. 热性惊厥相关癫痫患者抗癫痫药物治疗疗效及与电压依赖性钠通道α1亚基基因突变的关系%Efficacy of anti-epileptic drugs in patients with epilepsy with febrile seizures plus and the relation with voltage-gated sodium channel α1-subunit gene mutations

    Institute of Scientific and Technical Information of China (English)

    余璐; 何娜; 刘晓蓉; 黎冰梅; 徐海清; 石奕武; 高玫梅; 易咏红; 廖卫平

    2014-01-01

    Objective To analyze the efficacy of seizure control by anti-epileptic drugs (AEDs) in patients with epilepsy with febrile seizure plus (EFS +),and explore the proper medication choice in early stage of EFS + and its relation with voltage-gated sodium channel α1-subunit (SCN1A) gene mutations.Methods In 202 patients with EFS +,the data of detected voltage-gated SCN1A gene mutations and their treatment history by AEDs were retrospectively reviewed.The comparative analysis of efficacy of seizure control was performed in each AED administrated and further compared between EFS + patients with or without SCN1A gene mutations.Results Nine AEDs were administered in more than 10 cases,including valproate (VPA),topiramete (TPM),clonazepam (CNZ),phenobarbital (PB),levetiracetam (LEV),lamotrigine (LTG),carbamazepine (CBZ),oxcarbazepine (OXC) and phenytoin (PHT).Combined therapy was predominant (166/202,82.2%).Compared with other AEDs,the improvement rates were the highest in VPA (169/187,90.4%),TPM (111/120,92.5%) and CNZ (69/78,88.5% ;P =0.000),and were lowest in PHT and LTG (0 and 8.9% (4/45); P < 0.01).The improvement rate (58.1% (25/43) and 44.7% (21/47)) and no change rate (39.5% (17/43) and 48.9% (23/47)) of PB and LEV were approximately intermediate,without statistically significant difference between them but with statistically significant difference with others (P < 0.01).The aggravation rats of LTG and CBZ were the highest (57.8% (26/45) and 36.7% (18/49)) followed by OXC and PHT(33.3% (15/45) and 26.9% (7/26)).All of them showed statistically significant difference compared with others (P < 0.01).The aggravation rate of LTG in patients with SCN1A mutations (13/16,81.3%) was significantly higher than those without SCN1A mutations (13/29,44.8%),and there was statistically significant difference between them (x2 =5.607,P =0.018); similarly,the aggravation rates of CBZ,OXC and PHT showed an increased tendency,but no significant

  4. 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.

  5. 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 f

  6. 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.

  7. Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

    OpenAIRE

    Krasowski, Matthew D

    2010-01-01

    In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monito...

  8. Levetiracetam Induced Drug Reaction with Eosinophilia and Systemic Symptom Syndrome.

    Science.gov (United States)

    Dar, Waseem Raja; Sofi, Najeebullah; Latief, Muzamil; Dar, Imtiyaz Ahmad; Kasana, Basharat Ahmad

    2016-01-01

    Drug reaction with eosinophilia and systemic symptom syndrome (DRESS) is a hypersensitivity drug reaction, most frequently associated with antiepileptic drugs, characterized by skin rash, fever, pharyngitis, lymphadenopathy, and visceral organ involvement, typically presenting within 8 weeks of initiation of therapy. Management involves prompt withdrawal of the offending drug and use of systemic corticosteroids. We here present a rare case of DRESS secondary to levetiracetam. Only few case reports of DRESS secondary to levetiracetam have been published so far. PMID:27057042

  9. 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…

  10. 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.

  11. 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

  12. Transformation of the antiepileptic drug oxcarbazepine upon different water disinfection processes.

    Science.gov (United States)

    Li, Zhi; Fenet, Hélène; Gomez, Elena; Chiron, Serge

    2011-02-01

    Transformation of the pharmaceutical oxcarbazepine (OXC), a keto analogue of carbamazepine (CBZ) was investigated under different water disinfection processes (ozonation, chlorination and UV irradiation) to compare its persistence, toxicity and degradation pathways with those of CBZ. Analysis by LC-ion trap-MS(n) allowed for the identification of up to thirteen transformation products (TPs). The major abundant and persistent TPs (10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (DiOH-CBZ), acridine (ACIN) and 1-(2-benzaldehyde)-(1H, 3H)-quinazoline-2,4-dione (BQD)) were identical to those previously reported during water treatment of CBZ. Only one new compound arising from an intramolecular cyclisation reaction was identified during UV irradiation. OXC reacted quickly with hydroxyl radical and relatively rapidly with free chlorine while slow reaction rates were recorded in presence of ozone and upon UV irradiation. An increase of the acute toxicity of UV irradiated solutions, monitored by a Daphnia magna bioassay, was recorded, probably due to the accumulation of ACIN. The formation of ACIN is of concern due to the carcinogenic properties of this chemical. ACIN was also generated during the direct UV photo transformation of DiOH-CBZ and 10-hydroxy-10,11-dihydro-carbamazepine (OH-CBZ), two metabolites of OXC and CBZ widely detected in water resources. Analysis of tap water samples revealed the occurrence at ng/L levels of the major TPs detected under laboratory scale experiments, except ACIN.

  13. [Drugs from the classes of tricyclic antidepressives and antiepileptics, nitrosatable under simulated human gastric conditions].

    Science.gov (United States)

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

    The nitrosatability of Pryleugan (imipramine), Herphonal (trimipramine), and Finlepsin (carbamazepine) was investigated under simulated human gastric conditions using a colorimetric measuring method. All of them proved to be nitrosatable even at very low nitrite concentrations. In the presence of ascorbic acid, the formation of N-nitroso compounds under model conditions was inhibited markedly. N-nitroso-dihydrodibenzazepine and N-nitroso-dibenzazepine could be identified by thin layer chromatography as main products. The biological effects of these N-nitroso compounds are not known up to now. PMID:2802933

  14. 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

    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...

  15. [Pharmacogenetics and antiepileptic drug metabolism: implication of genetic variants in cytochromes P450].

    Science.gov (United States)

    Saldaña-Cruz, Ana Miriam; Sánchez-Corona, José; Márquez de Santiago, Daniel Alejandro; García-Zapién, Alejandra Guadalupe; Flores-Martínez, Silvia Esperanza

    2013-05-01

    Introduccion. Los farmacos antiepilepticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteinas implicadas en el metabolismo de algunos de los principales FAE, con enfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteinas involucradas en el metabolismo de farmacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clinica en el manejo terapeutico. La presencia de estas variantes geneticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapeutica, e incluso en la aparicion de efectos adversos. Conclusiones. La identificacion de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualizacion del tratamiento con la intencion de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clinica y los efectos adversos se presenten en una minoria de pacientes.

  16. Clinical Risk Factors Associated with Anti-Epileptic Drug Responsiveness in Canine Epilepsy

    OpenAIRE

    Packer, Rowena M. A.; Shihab, Nadia K.; Bruno B J Torres; Volk, Holger A

    2014-01-01

    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 ...

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    of 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...

  19. Effects of common anti-epileptic drugs on the serum levels of homocysteine and folic acid

    Directory of Open Access Journals (Sweden)

    Zamzam Paknahad

    2012-01-01

    Conclusions: Homocysteine (Hcy was not different between the epileptic and nonepileptic groups, although the means of the serum folic acid were similar. Possible mechanisms by which AEDs could cause hyper-homocysteinemia might be through the dysfunction of homocysteine metabolism, the acceleration of vitamin metabolism, and the interference in the metabolism of folic acid coenzymes.

  20. Outcome and antiepileptic drug policies after childhood epilepsy surgery in children

    NARCIS (Netherlands)

    Boshuisen, K.

    2015-01-01

    Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Of patients with newly diagnosed epilepsy, 70–80% respond well to medical treatment, while 20–30% develop intractable epilepsy. For intractable epilepsy patients with a clearly

  1. 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

    adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM...

  2. Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research.

    Science.gov (United States)

    Damar, U; Gersner, R; Johnstone, J T; Schachter, S; Rotenberg, A

    2016-06-01

    Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor extracted from Huperzia Serrata, a firmoss, which has been used for various diseases in traditional Chinese medicine for fever and inflammation. More recently, it has been used in Alzheimer's disease and other forms of dementia with a presumed mechanism of action via central nicotinic and muscarinic receptors. HupA is marketed as a dietary supplement in the U.S. This article reviews newly proposed neuroprotective and anticonvulsant HupA properties based on animal studies. HupA exerts its effects mainly via α7nAChRs and α4β2nAChRs, thereby producing a potent anti-inflammatory response by decreasing IL-1β, TNF-α protein expression, and suppressing transcriptional activation of NF-κB signaling. Thus, it provides protection from excitotoxicity and neuronal death as well as increase in GABAergic transmission associated with anticonvulsant activity. PMID:27086593

  3. [Prevalence, type of epilepsy and use of antiepileptic drugs in primary care].

    Science.gov (United States)

    Fernández-Suárez, Elena; Villa-Estébanez, Rubén; Garcia-Martinez, Alberto; Fidalgo-González, José A; Zanabili Al-Sibbai, Ahmad A; Salas-Puig, Javier

    2015-06-16

    Introduccion. La epilepsia es una enfermedad con gran repercusion social y economica. La prevalencia deberia ser usada como la base mas importante para planificar la prevencion secundaria y terciaria. Objetivos. Identificar los pacientes con diagnostico de epilepsia en un centro de atencion primaria y determinar la prevalencia, las caracteristicas demograficas, el tipo de sindrome epileptico y el uso de los farmacos antiepilepticos. Pacientes y metodos. Estudio descriptivo transversal retrospectivo. Incluyo 196 pacientes con diagnostico de epilepsia pertenecientes a un centro de salud y revision de la historia clinica hospitalaria, con el estudio de las variables sociodemograficas y clinicofarmacologicas. Resultados. Prevalencia de epilepsia: 8,4/1.000 habitantes. Edad media: 50,3 años. Sexo: 52,6%, hombres. Ambito: 79,6%, urbano. Antecedentes familiares de epilepsia: 14,8%. Tipo de epilepsia: focal sintomatica por ictus (14,3%), generalizada idiopatica (13,8%), focal criptogenica (8,7%), no clasificada (31,1%). Edad media al inicio de la crisis: 31,6 años. Comorbilidad neurologica o psiquiatrica: 62,8%. Ultima revision: el 18,9% sin tratamiento antiepileptico, el 56,6% en monoterapia y el 24,5% en politerapia. Libres de crisis: 76,5%. Farmacos mas prescritos: acido valproico, carbamacepina, fenitoina, lamotrigina y levetiracetam. Un 78,6% sin efectos secundarios. Fallecimiento: 4,1%. Conclusiones. La prevalencia de pacientes con epilepsia fue de 8,4/1.000 habitantes y predomina la focal sintomatica por ictus. Casi un tercio de los pacientes referia algun factor desencadenante de crisis, principalmente consumo de alcohol o fiebre. Predomina la monoterapia, los efectos secundarios son escasos y, en la ultima revision, la mayoria se hallaba libre de crisis.

  4. 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.

  5. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    Science.gov (United States)

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

  6. 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

    .5-448), of gabapentin with glaucoma (ASR 8.0; 95%CI 1.1-355) and of valproic acid with hypothyroidism (ASR 8.0; 95%CI 1.1-355). CONCLUSIONS: Few unsuspected adverse AED effects were recognized in our study. Sequence symmetry analysis is a feasible method of monitoring for adverse AED effects. Copyright (c) 2009 John...

  7. 新型抗癫痫药加巴喷丁%Gabapentin:a new antiepileptic drug

    Institute of Scientific and Technical Information of China (English)

    陈宝泉; 刘肖英; 李彩文

    2007-01-01

    加巴喷丁(gabapentin)是一种新型抗癫痫药,为γ-氨基丁酸(GABA)类似物,口服易吸收,与其他抗癫痫药物相互作用小,且耐受性好.临床研究表明,其作为添加用药治疗癫痫具有良好的临床疗效和安全性.现对其作用机制、药动学、药物相互作用、临床应用和药物不良反应等作一综述.

  8. Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy

    Directory of Open Access Journals (Sweden)

    S. Dwajani

    2014-08-01

    Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy. [Int J Basic Clin Pharmacol 2014; 3(4.000: 692-695

  9. 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 ...

  10. Role of adenosine in the antiepileptic effects of deep brain stimulation

    Science.gov (United States)

    Miranda, Maisa F.; Hamani, Clement; de Almeida, Antônio-Carlos G.; Amorim, Beatriz O.; Macedo, Carlos E.; Fernandes, Maria José S.; Nobrega, José N.; Aarão, Mayra C.; Madureira, Ana Paula; Rodrigues, Antônio M.; Andersen, Monica L.; Tufik, Sergio; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine. PMID:25324724

  11. Impact of variability in carbamazepine raw materials on drug release

    OpenAIRE

    Flicker, Felicia

    2011-01-01

    Variability in raw materials presents a challenge for pharmaceutical companies. The varying physicochemical properties can critically influence drug release and bioavailability of the final dosage form. Therefore, a strategy to control this variability is required. In this study the well-established antiepileptic drug carbamazepine (CBZ) was selected as the model drug as it presents one example where variability in raw materials has been linked to bioinequivalence and clinical failures. CBZ s...

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Drug: D00512 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00512 Drug Phenytoin (JP16/USP/INN); Dilantin (TN) C15H12N2O2 252.0899 252.268 D00...here is a strong association between the risk of developing SJS/TEN with Phenytoin treatment and the presenc...ystem 113 Antiepileptics 1132 Hydantoins D00512 Phenytoin (JP16/USP/INN) Anatomic...PTICS N03AB Hydantoin derivatives N03AB02 Phenytoin D00512 Phenytoin (JP16/USP/INN) USP drug classification ...[BR:br08302] Anticonvulsants Sodium Channel Agents Phenytoin D00512 Phenytoin (JP

  14. A new hypothesis of drug refractory epilepsy: neural network hypothesis.

    Science.gov (United States)

    Fang, Min; Xi, Zhi-Qin; Wu, Yuan; Wang, Xue-Feng

    2011-06-01

    Drug refractory is an important clinical problem in epilepsy, affecting a substantial number of patients globally. Mechanisms underlying drug refractory need to be understood to develop rational therapies. Current two prevailing theories on drug refractory epilepsy (DRE) include the target hypothesis and the transporter hypothesis. However, those hypotheses could not be adequate to explain the mechanisms of all the DRE. Thus, we propose another possible mechanism of DRE, which is neural network hypothesis. It is hypothesized that seizure-induced alterations of brain plasticity including axonal sprouting, synaptic reorganization, neurogenesis and gliosis could contribute to the formation of abnormal neural network, which has not only avoided the inhibitory effect of endogenous antiepileptic system but also prevented the traditional antiepileptic drugs from entering their targets, eventually leading to DRE. We will illustrate this hypothesis at molecular and structural level based on our recent studies and other related researches.

  15. 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

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

    Science.gov (United States)

    Lee, Jinsoo; Son, Kwanghyun; Hwang, Gwiseo; Kim, Moonju

    2016-01-01

    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. PMID:27047568

  17. 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.

  18. Compelling Diversity through Discrimination

    Science.gov (United States)

    Seligman, Clive

    2003-01-01

    Wilfrid Laurier University would consider only women for an opening in the psychology department, and credentials be damned. Clive Seligman protested on the grounds that the university's blatant attempt at social engineering fatally interferes with the epistemological mission of higher education. It confuses academic merit with biology, he…

  19. AED Treatment Through Different Ages: As Our Brains Change, Should Our Drug Choices Also?

    OpenAIRE

    French, Jacqueline A.; Staley, Brigid A.

    2012-01-01

    Patient age can impact selection of the optimal antiepileptic drug for a number of reasons. Changes in brain physiology from neonate to elderly, as well as changes in underlying etiologies of epilepsy, could potentially affect the ability of different drugs to control seizures. Unfortunately, much of this is speculative, as good studies demonstrating differences in efficacy across age ranges do not exist. Beyond the issue of efficacy, certain drugs may be more or less appropriate at different...

  20. [Drug resistant epilepsy. Clinical and neurobiological concepts].

    Science.gov (United States)

    Espinosa-Jovel, Camilo A; Sobrino-Mejía, Fidel E

    2015-08-16

    Drug-resistant epilepsy, is a condition defined by the International League Against Epilepsy as persistent seizures despite having used at least two appropriate and adequate antiepileptic drug treatments. Approximately 20-30% of patients with epilepsy are going to be resistant to antiepileptic drugs, with different patterns of clinical presentation, which are related to the biological basis of this disease (de novo resistance, relapsing-remitting and progressive). Drug resistant epilepsy, impacts negatively the quality of life and significantly increases the risk of premature death. From the neurobiological point of view, this medical condition is the result of the interaction of multiple variables related to the underlying disease, drug interactions and proper genetic aspects of each patient. Thanks to advances in pharmacogenetics and molecular biology research, currently some hypotheses may explain the cause of this condition and promote the study of new therapeutic options. Currently, overexpression of membrane transporters such as P-glycoprotein, appears to be one of the most important mechanisms in the development of drug resistant epilepsy. The objective of this review is to deepen the general aspects of this clinical condition, addressing the definition, epidemiology, differential diagnosis and the pathophysiological bases.

  1. Drug hypersensitivity syndrome.

    Science.gov (United States)

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    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. PMID:21220873

  2. 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.

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

    International Nuclear Information System (INIS)

    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

  4. 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.

  5. Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in an Adolescent Treated With Lamotrigine

    OpenAIRE

    Ginory, Almari; Chaney-Catchpole, Michelle; Demetree, Julie M.; Mayol Sabatier, Laura M.; Nguyen, Mathew

    2013-01-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome most commonly associated with antiepileptic agents, allopurinol, and sulfonamides. It is a severe adverse reaction associated with fever, rash, eosinophilia, lymphadenopathy, and internal organ involvement. We present the case of a 17-year-old Caucasian female with bipolar disorder type II and posttraumatic stress disorder treated with lamotrigine for a non-Food and Drug Administration-approved indica...

  6. 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

  7. The anti-epileptic drug valproic acid (VPA inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Claire Glister

    Full Text Available Valproic acid (VPA is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC and granulosa (GC cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001 with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05. VPA only reduced TC progesterone secretion induced by the highest (luteinizing LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001 by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001. The potent histone deacetylase (HDAC inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

  8. 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...

  9. 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 27m......M (logKm 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 that...

  10. Uptake of Three Antibiotics and an Antiepileptic Drug by Wheat Crops Spray Irrigated with Wastewater Treatment Plant Effluent.

    Science.gov (United States)

    Franklin, Alison M; Williams, Clinton F; Andrews, Danielle M; Woodward, Emily E; Watson, John E

    2016-03-01

    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 WWTP processes. Concern has arisen about the environmental fate of PPCPs, especially regarding plant uptake. The aim of this study was to analyze uptake of sulfamethoxazole, trimethoprim, ofloxacin, and carbamazepine in wheat ( L.) plants that were spray-irrigated with WWTP effluent. Wheat was collected before and during harvest, and plants were divided into grain and straw. Subsamples were rinsed with methanol to remove compounds adhering to surfaces. All plant tissues underwent liquid-solid extraction, solid-phase extraction cleanup, and liquid chromatography-tandem mass spectrometry analysis. Residues of each compound were present on most plant surfaces. Ofloxacin was found throughout the plant, with higher concentrations in the straw (10.2 ± 7.05 ng g) and lower concentrations in the grain (2.28 ± 0.89 ng g). Trimethoprim was found only on grain or straw surfaces, whereas carbamazepine and sulfamethoxazole were concentrated within the grain (1.88 ± 2.11 and 0.64 ± 0.37 ng g, respectively). These findings demonstrate that PPCPs can be taken up into wheat plants and adhere to plant surfaces when WWTP effluent is spray-irrigated. The presence of PPCPs within and on the surfaces of plants used as food sources raises the question of potential health risks for humans and animals.

  11. 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

    formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin....... The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems...

  12. Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.

    Science.gov (United States)

    Tolbert, Dwain; Bekersky, Ihor; Chu, Hui-May; Ette, Ene I

    2016-03-01

    A metabolic mechanism-based characterization of antiepileptic drug-drug interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach. To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability study OV-1017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of clobazam and its metabolite, N-desmethylclobazam (N-CLB): CYP3A inducers (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate, oxcarbazepine). CYP3A4 inducers-which did not affect the oral clearance of clobazam-significantly increased the formation of N-CLB by 9.4%, while CYP2C19 inducers significantly increased the apparent elimination rate of N-CLB by 10.5%, resulting in a negligible net change in the PK of the active metabolite. CYP2C19 inhibitors did not affect N-CLB elimination. Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here.

  13. The effect of community-based drug rehabilitation programs on recidivism in Malta

    OpenAIRE

    Axiak, Claire

    2016-01-01

    Background: The argument for financing therapeutic community-based drug rehabilitation programs for inmates is compelling. Numerous studies have established the positive effect of such treatment on reducing recidivism, especially treatment based on the therapeutic community model. Methods: This quasiexperimental retrospective cohort study examined the impact of therapeutic community-based drug rehabilitation programs on recidivism amongst drug inmates released from ...

  14. Deep brain stimulation of the posterior hypothalamus activates the histaminergic system to exert antiepileptic effect in rat pentylenetetrazol model.

    Science.gov (United States)

    Nishida, Namiko; Huang, Zhi-Li; Mikuni, Nobuhiro; Miura, Yoshiki; Urade, Yoshihiro; Hashimoto, Nobuo

    2007-05-01

    Deep brain stimulation (DBS) is a promising therapy for intractable epilepsy, yet the optimum target and underlying mechanism remain controversial. We used the rat pentylenetetrazol (PTZ) seizure model to evaluate the effectiveness of DBS to three targets: two known to be critical for arousal, the histaminergic tuberomammillary nucleus (TMN) and the orexin/hypocretinergic perifornical area (PFN), and the anterior thalamic nuclei (ATH) now in clinical trial. TMN stimulation provided the strong protection against the seizure, and PFN stimulation elicited a moderate effect yet accompanying abnormal behavior in 25% subjects, while ATH stimulation aggravated the seizure. Power density analysis showed EEG desynchronization after DBS on TMN and PFN, while DBS on ATH caused no effect with the same stimulation intensity. EEG desynchronization after TMN stimulation was inhibited in a dose-dependent manner by pyrilamine, a histamine H(1) receptor selective antagonist, while the effect of PFN stimulation was inhibited even at a low dose. In parallel, in vivo microdialysis revealed a prominent increase of histamine release in the frontal cortex after TMN stimulation, a moderate level with PFN and none with ATH. Furthermore, antiepileptic effect of DBS to TMN was also blocked by an H(1) receptor antagonist. This study clearly indicates that EEG desynchronization and the activation of the histaminergic system contributed to the antiepileptic effects caused by DBS to the posterior hypothalamus.

  15. The management of drug resistant seizures in tuberous sclerosis

    Directory of Open Access Journals (Sweden)

    Romina MOAVERO

    2009-12-01

    Full Text Available Tuberous Sclerosis Complex (TSC is a multisystem autosomal dominant genetic disorder resulting from mutations in one of two genes, TSC1 and TSC2. Pathologically TSC is characterized by abnormal cellular differentiation and proliferation, as well as abnormal neuronal migration. The majority of patients with TSC have epilepsy, although the mechanisms underlying epileptogenesis remain unknown. Seizures onset is frequently during the first year of life, and in a sizable proportion of individuals tend to be refractory to antiepileptic drug treatment. This article reviews the progress in understanding drug resistant seizures in TSC, from molecular pathogenesis to the pathophysiological mechanisms of epileptogenesis, and the rationale for appropriate medical and surgical treatment.

  16. Molecular Genetics of Drug-resistance in Epilepsies

    OpenAIRE

    Kurupath Radhakrishnan

    2015-01-01

    Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2...

  17. 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 clozapine in 2 patients with schizophrenia, who both suffered from severe anxiety symptoms. RESULTS: Both patients experienced falls and consequently bone fractures. Increased plasma levels of clozapine likely contributed to the outcome. One patient had confirmed seizures whereas the mechanism in the other...

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

    Science.gov (United States)

    Fusco, Ferdinando; Franco, Marco; Longo, Nicola; Palmieri, Alessandro; Mirone, Vincenzo

    2014-03-01

    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. PMID:24704935

  19. 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.

  20. Antiepileptic and neuroprotective effects of human umbilical cord blood mononuclear cells in a pilocarpine-induced epilepsy model.

    Science.gov (United States)

    Costa-Ferro, Zaquer Suzana Munhoz; de Borba Cunha, Fernanda; de Freitas Souza, Bruno Solano; Leal, Marcos Maurício Tosta; da Silva, Adelson Alves; de Bellis Kühn, Telma Ingrid Borges; Forte, Andresa; Sekiya, Eliseo Joji; Soares, Milena Botelho Pereira; Dos Santos, Ricardo Ribeiro

    2014-03-01

    Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.

  1. Health care organization drug testing.

    Science.gov (United States)

    Brooks, J P; Dempsey, J

    1992-09-01

    Health care managers are being required to respond to the growing concerns of the public about alcohol and drug use in the health care workplace. To this end, the following recommendations are offered. A drug testing policy should be developed with input from and support of employees and unions. "For cause" testing should be used because it results in more definitive results and better employee acceptance. Unless there are compelling reasons for random testing, "for cause" testing is the preferable method. All levels of employees and the medical staff should be subject to the drug-testing policy. Rehabilitation rather than punishment should be emphasized in dealing with employees with alcohol and drug problems.

  2. Emerging drugs for partial-onset epilepsy: a review of brivaracetam

    Directory of Open Access Journals (Sweden)

    Gao L

    2016-05-01

    Full Text Available Lan Gao,1 Shuchuen Li2 1Deakin Population Health SRC, Faculty of Health, Deakin University, Burwood, Victoria, 2School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia Abstract: There are more than 12 new antiepileptic drugs approved in the last 2 decades. Even with these newer agents, seizure remission is still unachievable in around 30% of patients with partial-onset seizures (POS. Brivaracetam (BRV is chemically related to levetiracetam (LEV and possesses a strong binding affinity for the synaptic vesicle protein 2A tenfold above that of LEV, and other possible modes of antiepileptic actions. BRV is now under Phase III development for POS, but data from one Phase III trial also suggested its potential efficacy for primary generalized seizures. The purpose of this review is to provide updated information on the mechanisms of action of the available antiepileptic drugs, with a focus on BRV to assess its pharmacology, pharmacokinetics, clinical efficacy, safety, and tolerability in patients with uncontrolled POS. To date, six Phase IIb and III clinical trials have been performed to investigate the efficacy, safety, and tolerability of BRV as an adjunctive treatment for patients with POS. Generally, BRV was well tolerated and did not show significant difference in safety profile, compared to placebo. The efficacy outcomes of BRV, although not consistent across trials, did indicate that BRV was a promising add-on therapy for patients with POS. In conclusion, the many favorable attributes of BRV, like its high oral efficacy, good tolerability, dosing regimen, and minimal drug interaction, make it a promising antiepileptic therapy for patients with uncontrolled partial-onset epilepsy. Keywords: brivaracetam, partial-onset epilepsy, drug-resistant epilepsy, randomized controlled trial, review

  3. 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.

  4. 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...

  5. Pattern of drug eruptions in a tertiary care hospital

    International Nuclear Information System (INIS)

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

  6. Analysis of reasons for low adherence to antiepileptic therapy in patients with symptomatic epilepsy

    Directory of Open Access Journals (Sweden)

    M. A. Vagina

    2014-01-01

    Full Text Available Objective: to study the major factors that influence treatment adherence.Patients and methods. One hundred patients aged 20 to 68 years (mean age 42.9±3.0 years for women and 43.3±5.0 years for men diagnosed with a ≥3-year history of symptomatic epilepsy were screened. The minimal and maximal durations of the disease were 5 and 59 years, respectively (mean 20.8±3.9 years.Results and discussion. There was a female preponderance in the treatment adherence group. The patients who had secondary special education were unemployed, disabled, and single were in both comparison groups. These data are indicative of social stigmatization in epileptic patients. Patients with severe epilepsy on multiple drug therapy were prevalent. Neuropsychological testing revealed higher levels of anxiety and depression among those who were non-adherent to therapy.Conclusion. The sex, age, and social characteristics (education level, disability of patients with epilepsy and its clinical picture, neurological symptoms and changes were ascertained by magnetic resonance imaging had no significant impact on therapy adherence.The factors influencing treatment adherence should include multiple drug therapy (co-administration of two or three drugs and the high frequency of drug use, which is more frequently observed in patients with severe treatment-resistant epilepsy. Anxiety and depressive disorders in epileptic patients resulted in impaired compliance with anticonvulsant therapy.

  7. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were ...

  8. Status report 1976 on radioprotective action of some drugs

    International Nuclear Information System (INIS)

    The radioprotecting effect of several tranquilizers or antiepileptic drugs (Equanil, Largactil, Nozinan, Depakine, Rimifon, Polaramine, Insulin, Glutamag, Transfusine), against gamma radiation was investigated in mice. The radiation dose was LD 100/30 (evaluated to be between 900 and 1000 R as a function of mice strain). The tests performed were based on the evaluation of survival fractions after 30 days. The mice were given the drugs at the maximum tolerated dose. For each drug, the following results were given: MST 30 which is the mean survival time calculated for a 30 days period and ST 50 which is the time leading to 50% survivors. Among the various drugs tested Polaramine led to the best results

  9. Flurbiprofen-induced generalized bullous fixed drug eruption.

    Science.gov (United States)

    Balta, I; Simsek, H; Simsek, G G

    2014-01-01

    Fixed drug eruption (FDE) is an unusual drug-related side effect that results in recurrent lesions whenever the causative drugs are used. FDEs usually occur as a single, sharply demarcated, round erythematous patch or plaque, occasionally with localized bullae. The most common offending agents include antimicrobials, nonsteroidal anti-inflammatory drugs, and antiepileptics. There are some reports where contact dermatitis and cutaneous vasculitis have been associated with the use of flurbiprofen. We present the case of a 50-year-old man with flurbiprofen-induced generalized bullous FDE. To the best of our knowledge, the most serious form of FDE, the generalized bullous FDE, to be caused by flurbiprofen has not been reported previously.

  10. Determination of the antiepileptics vigabatrin and gabapentin in dosage forms and biological fluids using Hantzsch reaction.

    Science.gov (United States)

    al-Zehouri, J; al-Madi, S; Belal, F

    2001-02-01

    A selective and sensitive method was developed for the determination of the anticonvulsants vigabatrin (I) (CAS 60643-86-9) and gabapentin (II) (CAS 60142-96-3). The method is based on the condensation of the drugs through their amino groups with acetylacetone and formaldehyde according to Hantzsch reaction yeilding the highly fluorescent dihydropyridine derivatives. The yellowish-orange color was also measured spectrophotometrically at 410 nm and 415 nm for I and II, respectively. The absorbance-concentration plots were rectilinear over the ranges 10-70 micrograms/ml and 20-140 micrograms/ml for I and II, respectively. As for the fluorescence-concentration plots, they were linear over the ranges 0.5-10 micrograms/ml and 2.5-20 micrograms/ml with minimum detection limits (S/N = 2) of 0.05 microgram/ml (approximately 2.1 x 10(-8) mol/l) and 0.1 microgram/ml (approximately 5.8 x 10(-7) mol/l) for I and II, respectively. The spectrophotometric method was applied to the determination of I and II in their tablets. The percentage recoveries +/- SD (n = 6) were 99.45 +/- 0.13 and 98.05 +/- 0.53, respectively. The spectrofluorimetric method was successfully applied to the determination of I and II in spiked human urine and plasma. The % recoveries +/- SD (n = 5) were 98.77 +/- 0.29 and 98.39 +/- 0.53 for urine and 99.32 +/- 0.74 and 98.90 +/- 0.96 for plasma, for I and II, respectively. No interference was encountered with the co-administered drugs: valproic acid (CAS 99-66-1), diphenylhydantoin (CAS 57-41-0), phenobarbital (CAS 50-06-6), carbamazepine (CAS 298-46-4), clonazepam (CAS 1622-61-3), clobazam (CAS 22316-47-8) or cimetidine (CAS 51481-61-9). A proposal of the reaction pathway is suggested. The advantages of the proposed methods over existing method are discussed. PMID:11258050

  11. 治疗药物监测临床应用现状%Clinical application of therapeutic drug monitoring

    Institute of Scientific and Technical Information of China (English)

    陈婷; 梅义将

    2012-01-01

    回顾治疗药物监测(TDM)的临床应用等,本文重点综述抗癫痫药物与免疫抑制约物的TDM临床应用评价,分析开展TDM过程中存在的问题.%To retrospect the application of therapeutic drug monitoring (TDM), this review focuses on the clinical evaluation of anti-epileptic drugs and immunosuppressive drugs, and some problems in the TDM processes.

  12. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn ...

  13. Drug Facts

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    Full Text Available ... Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug ...

  14. Central Nervous System Drug Development: An Integrative Biomarker Approach toward Individualized Medicine

    OpenAIRE

    Gomez-Mancilla, B.; Marrer, E.; Kehren, J.; Kinnunen, A. (Aulis); Imbert, G.; Hillebrand, R.; Bergström, M.; Schmidt, M. E.

    2005-01-01

    Summary: Drug development for CNS disorders faces the same formidable hurdles as other therapeutic areas: escalating development costs; novel drug targets with unproven therapeutic potential; and health care systems and regulatory agencies demanding more compelling demonstrations of the value of new drug products. Extensive clinical testing remains the core of registration of new compounds; however, traditional clinical trial methods are falling short in overcoming these development hurdles. ...

  15. [Interactions between oral contraceptives and other drugs].

    Science.gov (United States)

    Hansen, T H; Jensen, S B

    1991-10-28

    Failures of oral contraceptives are possible when combined with rifampicin or antiepileptics, especially phenobarbitone and phenytoin. The mode of action is shown by clinical trials to be due to induction of hepatic enzymes thus increasing the steroid metabolism. Failure or oral contraceptives has occurred with the concomitant use of antibiotics, i.e. ampicillin and sulfonamides. Clinical trials have focused upon the changes in the intestinal flora induced by antibiotics. This might influence the enterohepatic circulation of estrogen and thereby decrease reabsorption of estrogen, but this has not been definitely proved. The failures may be caused by individual pharmacokinetics of oral contraceptives. Oral contraceptives are able to influence the pharmacodynamics of various other drugs metabolized by oxidation or conjugation but besides an increased pharmacological effect of prednisolone and increased toxicity of imipramine the clinical importance is uncertain. PMID:1949335

  16. 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. PMID:26535466

  17. Drug Facts

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    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug Abuse and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? ...

  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. Drug-induced status epilepticus.

    Science.gov (United States)

    Cock, Hannah R

    2015-08-01

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

  20. [Drug interactions with contraceptive methods].

    Science.gov (United States)

    Simon, P; Hakkou, F; Warot, D

    1984-03-01

    3 possible types of drug interactions with contraceptives involve oral contraceptives (OCs), IUDs, and spermicides. The interaction of combined OCs with various drugs is frequently discussed in the literature, but the reported facts are sometimes contradictory. Case studies have indicated failure of OCs in patients taking ampicillin, but comparative studies using ampicillin and placebos have shown no difference in rates of estrogen, progestogens, follicle stimulating hormone, or luteinizing hormone in the 2 groups. Individual differences and predispositions among some women appear to play a role in drug interactions. The clinician should be wary of modifying accepted prescription practices too readily in the face of findings that may be explained by other as yet undisclosed factors. Interactions are difficult to establish, as are their mechanisms. They may perhaps be explained by the estrogen or progestogen components of the pills, the timing of the antibiotic dose, the duration of treatment and the dosage used, resistance of the intestinal flora, self-medication, or other factors. The drug troleandomycin is a special case; it appears to favor the already existing tendency of OCs to provoke cholestatic jaundice. A table of drug interactions with OCs can be divided into 2 parts, those that have been confirmed and whose mechanisms of action are known, including antiepileptics such as phenobarbital, butobarbital, phenytoin, and primidone, and the drug rifampicin, which are enzyme inductors; and those that are suspected but as yet unconfirmed and whose mechanism of action is not established. The unconfirmed interactions involve a variety of effects in addition to pregnancy. It is not yet established whether enzyme inductors are a greater problem for users of low-dose pills, but the probable existence of individual variations in sensitivity causes problems in setting recommendations applicable to all patients. Interactions between progestogen-only OCs and other drugs

  1. Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

    Science.gov (United States)

    Rocha, Luisa; Cuellar-Herrera, Manola; Velasco, Marcos; Velasco, Francisco; Velasco, Ana-Luisa; Jiménez, Fiacro; Orozco-Suarez, Sandra; Borsodi, Anna

    2007-10-01

    Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.

  2. New drug classes for the treatment of partial onset epilepsy: focus on perampanel

    Directory of Open Access Journals (Sweden)

    Shih JJ

    2013-07-01

    Full Text Available Jerry J Shih,1 William O Tatum,1 Leslie A Rudzinski21Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; 2Department of Neurology, Emory University, Atlanta, GA, USAAbstract: Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile hydrate is the latest in the line of new antiepileptic drugs with a novel mechanism of action. Perampanel inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA-induced increases in intracellular Ca2+ and selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing neuronal excitation. Three Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated the efficacy and good tolerability of perampanel as adjunctive treatment in patients with refractory partial-onset seizures. The drug is approved for use in the European Union and United States, with expected release onto the American market in June–September 2013, pending US Drug Enforcement Agency classification. The pharmacology of perampanel offers potential as more than just another new antiepileptic drug. This first-in-class drug will provide another option for practitioners of rational polytherapy. As an AMPA-receptor antagonist, perampanel may possess antiepileptogenic properties in addition to its demonstrated antiseizure properties.Keywords: perampanel, mechanism of action, efficacy, review

  3. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  4. Generic Drugs

    Science.gov (United States)

    ... name drug. A brand- name drug has a patent. When the patent runs out— usually after 10 to 14 years— ... if you do not have drug coverage. Condition Diabetes Heart failure High cholesterol Migraine Brand-name drug ...

  5. Drug Facts

    Science.gov (United States)

    ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  6. 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.

  7. Interrater reliability of the international consensus definition of drug-resistant epilepsy: a pilot study.

    Science.gov (United States)

    Hao, Xiao-ting; Wong, Irina S M; Kwan, Patrick

    2011-10-01

    We evaluated the interrater reliability of the consensus definition of drug-resistant epilepsy proposed by the International League Against Epilepsy. According to the definition framework, outcome of each antiepileptic drug (AED) trial was categorized as "seizure freedom" or "treatment failure." This level 1 assessment was used to determine the level 2 classification, which defined drug-resistant epilepsy as the failure of adequate trials of two or more AED schedules to achieve sustained seizure freedom. Two raters classified treatment outcomes of 150 patients independently. The patients had received a total of 428 trials of AEDs. Categorization of level 1 outcome to individual AED trials by the raters was consistent in 413 (96.5%). For the level 2 classification of drug-resistant or drug-responsive epilepsy, there was absolute agreement between the raters in 141 patients (94%), with a κ index of 0.91 (Pdefinition appeared to have a high degree of interrater reliability in this setting.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children ... a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free ...

  9. EFFICACY OF VIMPAT (LACOSAMIDE TN THE TREATMENT OF DRUG-RESISTANT CRYPTOGENIC FOCAL EPILEPSY WITH FOCAL AUTOMOTOR AND SECONDARILY GENERALIZED SEIZURES (A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    M. B. Mironov

    2015-07-01

    Full Text Available Despite the considerable advances of epileptology drug-resistant epilepsies consist about 30% among all forms of epilepsy. A case of successful using of a new antiepileptic drug lacosamide (vimpat in the treatment of 31 years old patient with the resistant form of cryptogenic focal epilepsy with focal automotor and secondarily generalized seizures is presented. Authors represent the review of the literature devoted to efficacy and tolerability of lacosamide in the treatment of drug-resistant epilepsy.

  10. Drug: D00538 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (6323) Dopaminergic synapse Enzyme: CYP3A4 [HSA:1576] map07033 Anticonvulsants map07057 Antiparkins...m 113 Antiepileptics 1139 Others D00538 Zonisamide (JAN/USAN/INN) 116 Antiparkinsonian agents 1169 Others D0

  11. Prescription Drugs

    Science.gov (United States)

    ... Us Search Search close Teens Teachers Parents Drugs & Health Blog NDAFW Enter Search Term(s): Teens / Drug Facts / Prescription Drugs Prescription Drugs Print What Is Prescription Drug Abuse? Also known as: Opioids: Hillbilly heroin, oxy, OC, oxycotton, percs, happy pills, vikes Depressants: ...

  12. Triazolines XV. Anticonvulsant profile of ADD 17014, a potentially unique 1,2,3-triazoline antiepileptic drug, in mice and rats.

    Science.gov (United States)

    Kadaba, P K; Slevin, J T

    1988-01-01

    ADD 17014[1-(4-chlorophenyl)-5-(4-pyridyl) delta 2-1,2,3-triazoline], is a representative member of a hitherto unknown, structurally novel family of anticonvulsant agents. The anticonvulsant profile of ADD 17014 following intraperitoneal (i.p.) and oral administration in mice and rats was evaluated using a battery of well-standardized anticonvulsant tests and compared with phenytoin (PHT), phenobarbital (PB), ethosuximide (ESM), and valproate (VPA). The results indicate that ADD 17014 is effective in nontoxic i.p. doses in mice by the maximal electroshock seizure (MES), Metrazol (subcutaneous, s.c. Met), bicuculline (s.c. Bic) and picrotoxin (s.c. Pic) tests, but ineffective against strychnine-induced seizures; it is also effective after nontoxic oral doses in both mice and rats by the MES and s.c. Met tests. Protective indices (PI = TD50/ED50), calculated from i.p. data in mice, were highest for ADD 17014 by the s.c. Met (26.02) and s.c. Bic (93.93) tests; the PIs, after oral administration in mice and rats, were equal to or higher than those of the prototype agents. In vitro receptor binding studies of ADD 17014 and potential metabolites indicated no significant inhibitory activity except for the beta-amino alcohol, which displaced almost 93% of [3H]glutamate from the glutamate receptors, suggesting that ADD 17014 may be functioning as a prodrug and an excitatory amino acid antagonist. The overall results indicate that ADD 17014 is a relatively nontoxic agent that more closely resembles PB and VPA, with a broad and unique spectrum of anticonvulsant activity. PMID:3371287

  13. A novel antiepileptic drug-eslicarbazepine acetate%新型抗癫痫药醋酸艾司利卡西平

    Institute of Scientific and Technical Information of China (English)

    赵蕾蕾; 杜小莉; 徐小薇

    2014-01-01

    癫痫是一种常见的脑部疾病,由大脑神经元的反复异常放电引起.尽管目前有很多种抗癫痫药物可用,但是约30%的患者存在抗药性或者用药过程中出现了严重的不良反应.醋酸艾司利卡西平是卡马西平的衍生物,由Sunovion Pharmaceuticals Inc.公司研究开发,用于伴有或不伴有继发性全身发作的成人癫痫部分性发作的治疗.它是一种新型电压门控钠通道抑制剂,通过阻断动作电位的传导,以抑制脑神经元的反复异常放电,控制癫痫发作.本文对其作用机制、药动学、药效动力学、临床研究、安全性评价等做一介绍.

  14. Treatment Effects of Onion (Allium cepa) and Ginger (Zingiber officinale) on Sexual Behavior of Rat after Inducing an Antiepileptic Drug (lamotrigine)

    OpenAIRE

    Khaki, Arash; Farnam, Alireza; Badie, Arash Davatgar; Nikniaz, Hussein

    2012-01-01

    Objective: The aim of the present study was to evaluate the beneficial degree of sexual behavior in male rats after inducement of onion and ginger in lamotrigine receiving groups. Material and Methods: Wistar rats (n=70) (male=35, female=35) were allocated so that males were divided into seven groups: control (n=5) and test groups (n=35). Control group used normal Saline (3 cc for each rat). Lamotrigine group were given Lamotrigine (10 mg/kg). Onion group used onion fresh juice (3 ...

  15. Anticonvulsant activity, neural tube defect induction, mutagenicity and pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide.

    Science.gov (United States)

    Sobol, Eyal; Yagen, Boris; Lamb, John G; White, H Steve; Wlodarczyk, Bogdan J; Finnell, Richard H; Bialer, Meir

    2007-01-01

    N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide (OM-TMCD) is a methoxyamide derivative of a cyclopropyl analogue of valproic acid (VPA). The structural considerations used in the design of OM-TMCD were aimed to enhance OM-TMCD anticonvulsant potency (compared to VPA) and to prevent VPA's two life-threatening side effects, i.e., induction of neural tube defects (NTDs) and hepatotoxicity. Following i.p. administration to rats OM-TMCD demonstrated a broad spectrum of anticonvulsant activity and showed better potency than VPA in the maximal electroshock seizure and subcutaneous pentylenetetrazole tests as well as in the hippocampal kindling model. OM-TMCD was inactive in the mouse 6-Hz test at 100 mg/kg dose. Teratogenicity studies performed in a SWV/Fnn-mouse model for VPA-induced-exencephaly showed that on the equimolar basis OM-TMCD possesses the same fetal toxicity and ability to induce NTDs as VPA, but since OM-TMCD is a much more potent anticonvulsant its activity/exencephaly formation ratio appears to be much more beneficial than that of VPA. OM-TMCD was found to be non-mutagenic and non-pro-mutagenic in the Ames test. It showed a beneficial pharmacokinetic profile in rats, having a high oral bioavailability of 75% and satisfactory values of clearance and volume of distribution. These results support further studies to fully characterize the therapeutic potential of OM-TMCD.

  16. Primidone - An antiepileptic drug - characterisation by quantum chemical and spectroscopic (FTIR, FT-Raman, 1H, 13C NMR and UV-Visible) investigations

    Science.gov (United States)

    Arjunan, V.; Santhanam, R.; Subramanian, S.; Mohan, S.

    2013-05-01

    The solid phase FTIR and FT-Raman spectra of primidone were recorded in the regions 4000-400 cm-1 and 4000-100 cm-1, respectively. The vibrational spectra were analysed and the observed fundamentals were assigned and analysed. The experimental wavenumbers were compared with the theoretical scaled vibrational wavenumbers determined by DFT methods. The Raman intensities were also determined with B3LYP/6-31G(d,p) method. The total electron density and molecular electrostatic potential surface of the molecule were constructed by using B3LYP/6-311++G(d,p) method to display electrostatic potential (electron + nuclei) distribution. The HOMO and LUMO energies were measured. Natural bond orbital analysis of primidone has been performed to indicate the presence of intramolecular charge transfer. The 1H and 13C NMR spectra were recorded and the chemical shifts of the molecule were calculated.

  17. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  18. Club Drugs

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Learn more Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  20. Drug Reactions

    Science.gov (United States)

    ... 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 ...

  1. Pharmacological Treatment of Drug-Resistant Epilepsy in Adults: a Practical Guide.

    Science.gov (United States)

    Brodie, Martin J

    2016-09-01

    More than 30 % of adults with epilepsy do not fully control on the currently available antiepileptic drugs (AEDs). For these and many other patients, combinations of agents, often possessing different mechanisms of actions, are employed with the aim of achieving seizure freedom or the best available prognosis in terms of reduced seizure numbers and severity. This review discusses my own approach to optimising outcomes in as many of these patients as possible by adjusting the drug burden using a combination of two, three or sometimes four or more AEDs. Modes of drug action are reviewed and practical strategies for treating different patients with drug-resistant epilepsy have been explored. Only for sodium valproate with lamotrigine is there good evidence of synergism. The final part of this practical paper consists of six individual illustrative cases with appropriate comments. PMID:27443649

  2. Advance of drug-resistant epilepsy's definition and its application%耐药性癫(癎)的定义及其应用进展

    Institute of Scientific and Technical Information of China (English)

    吴勇; 廖建湘

    2015-01-01

    In the use of antiepileptic drugs in patients with epilepsy,1/3 of the patients with epilepsy can not get effective control,showing resistance to antiepileptic drugs.Now the mechanism of drug resistance is considered to be caused by multiple factors work together.The concept and connotation between drug-resistant epilepsy and refractory epilepsy are different.Since 2010,the international union of antiepileptic proposed " drug-resistant epilepsy" expert consensus,different medical centers use the new defition to study different populations and confirm that the new definition is effective and reliable.However,there are some controversier about the drug dosage,drug kinds,judge for determining evaluation index and the treatment judgement in that definition.%使用抗癫(癎)药物治疗的癫(癎)患者中,大约1/3癫(癎)发作不能得到有效控制,表现为对抗癫(癎)药物耐药.耐药性产生的机制目前考虑可能是多种因素共同作用所致.耐药性癫(癎)与难治性癫(癎)2个概念语义及内涵存在区别.自2010年国际抗癫(癎)联盟提出“耐药性癫(癎)”定义的专家共识以来,不同医疗中心应用新定义标准针对不同人群进行研究,证实新定义的有效性和可靠性较好,同时对于定义中药物剂量、药物种类、评判时间、治疗结果判定等评价指标的设定存在争议.

  3. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

    Science.gov (United States)

    Kwan, Patrick; Arzimanoglou, Alexis; Berg, Anne T; Brodie, Martin J; Allen Hauser, W; Mathern, Gary; Moshé, Solomon L; Perucca, Emilio; Wiebe, Samuel; French, Jacqueline

    2010-06-01

    To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.

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

    Directory of Open Access Journals (Sweden)

    Priscila de Freitas-Lima

    2013-11-01

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

  5. Drug Abuse

    Science.gov (United States)

    ... as drugged driving, violence, stress, 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 abuse. But the best is to prevent drug ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  7. Analgesic drugs

    OpenAIRE

    Kerec Kos, Mojca

    2015-01-01

    In the management of pain analgesic drugs are chosen regarding the intensity and type of pain. The selection of analgesic drug depends on pharmacokinetic properties of the drug and available pharmaceutical dosage forms. Beside non-opioid analgesics (non-steroidal antiinflammatory drugs, acetaminophen), opioid analgesic drugs have an important role in the treatment of pain. Pri zdravljenju bolečine izberemo analgetik glede na jakost in vrsto bolečine. Na izbiro ustreznega analgetika vplivaj...

  8. 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.

  9. 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 use; Hypnotic - substance ...

  10. [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. PMID:20095393

  11. [Severe drug-induced skin reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis].

    Science.gov (United States)

    Mockenhaupt, M

    2014-05-01

    Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are characterized by extensive blistering of the skin and mucosa; they are considered as one disease entity with varying severity. They are rare but potentially life-threatening and accompanied by high mortality. A clear clinical diagnosis is needed to direct specific therapy, but supportive therapy remains most important. In order to identify and withdraw the inducing drug, a very detailed and thorough medication history has to be obtained. Among the highly suspected (strongly associated) agents are allopurinol, antibacterial sulfonamides, non-steroidal anti-inflammatory drugs of the oxicam type, various anti-epileptics and nevaripine. Together they account for more than half of the cases of SJS/TEN. Although a drug is not always the cause, it is considered very like in approximately 75% of cases. Infections have also to be considered as etiologic factors. PMID:24820799

  12. 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

  13. Epilepsy drugs and effects on fetal development: Potential mechanisms

    Directory of Open Access Journals (Sweden)

    Leila Etemad

    2012-01-01

    Full Text Available Approximately 1% of all pregnancies are in woman with epilepsy. Although, the majority of children born to women with epilepsy are normal, they are at increased risk for malformations. Notably, the teratogenicity of antiepileptic drugs is a well-defined subject. The incidence of major malformations in offspring of mothers with epilepsy who were treated with AEDs is higher than women with untreated epilepsy and in the general population. These malformations include spina bifida, cleft palate, limb reduction defects, cardiac abnormalities, hypospadias, and gastrointestinal atresia. The exact mechanism by which the AEDs mediate abnormalities in the fetus is uncertain. However, there are several hypotheses to explain them. Some of the most important include folate-related actions, ischemia, reactive intermediates (e.g., free radicals, and genetic susceptibility. Thus, understanding the mechanisms of AED-related abnormalities is of vital importance for the care of epileptic women and their offspring.

  14. Epilepsy drugs and effects on fetal development: Potential mechanisms.

    Science.gov (United States)

    Etemad, Leila; Moshiri, Mohammad; Moallem, Seyed Adel

    2012-09-01

    Approximately 1% of all pregnancies are in woman with epilepsy. Although, the majority of children born to women with epilepsy are normal, they are at increased risk for malformations. Notably, the teratogenicity of antiepileptic drugs is a well-defined subject. The incidence of major malformations in offspring of mothers with epilepsy who were treated with AEDs is higher than women with untreated epilepsy and in the general population. These malformations include spina bifida, cleft palate, limb reduction defects, cardiac abnormalities, hypospadias, and gastrointestinal atresia. The exact mechanism by which the AEDs mediate abnormalities in the fetus is uncertain. However, there are several hypotheses to explain them. Some of the most important include folate-related actions, ischemia, reactive intermediates (e.g., free radicals), and genetic susceptibility. Thus, understanding the mechanisms of AED-related abnormalities is of vital importance for the care of epileptic women and their offspring. PMID:23826017

  15. Drug Facts

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    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts Meth (Crank, Ice) Facts Pain ... Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can ...

  16. 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 Cocaine Heroin Marijuana Meth Pain ...

  17. Drug Facts

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    Full Text Available Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ...

  18. Drug Facts

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    Full Text Available ... People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, ... and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs ...

  19. Drug Facts

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    Full Text Available ... People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs ...

  20. Drug Facts

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

  1. Drug Facts

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    Full Text Available ... Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between ... This Website Tools and Resources | Contact Us | Site Map | Accessibility | Privacy | FOIA (NIH) The National Institute on ...

  2. Drug Facts

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    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, ... Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What is Addiction? Do You or a Loved ...

  3. Drug Facts

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    Full Text Available ... Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts Meth ( ... treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You ...

  4. Drug Addiction

    OpenAIRE

    Justinova, Zuzana; Panlilio, Leigh V; Goldberg, Steven R.

    2009-01-01

    Many drugs of abuse, including cannabinoids, opioids, alcohol and nicotine, can alter the levels of endocannabinoids in the brain. Recent studies show that release of endocannabinoids in the ventral tegmental area can modulate the reward-related effects of dopamine and might therefore be an important neurobiological mechanism underlying drug addiction. There is strong evidence that the endocannabinoid system is involved in drug-seeking behavior (especially behavior that is reinforced by drug-...

  5. Medicaid Drugs

    OpenAIRE

    Poisal, John A.

    2004-01-01

    The following commentary unites a collection of articles primarily concerned with prescription drug issues in Medicaid. It also features highlights from a piece outlining Australia's pharmaceutical delivery system. Specifically, in this issue, you will find comprehensive analyses of drug expenditure trends, issues regarding access to pharmaceuticals in Medicaid, and an evaluation of ongoing generic drug cost-containment programs.

  6. Drug Facts

    Medline Plus

    Full Text Available ... Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment centers near ... different people around me. To stop using marijuana, "Cristina" is making positive changes in her life. ...

  7. 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.

  8. Progress of the antiepileptic mechanisms of ketogenic diet%生酮饮食抗癫(疒间)机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    姬辛娜; 秦炯

    2010-01-01

    生酮饮食(ketogenic diet,KD)是一种高脂低糖低蛋白饮食,直接引发酮体、脂肪酸升高以及糖酵解抑制等全身性变化.癫疒间发病机制主要与离子通道、神经递质和神经细胞损伤等相关.该文着重从癫(疒间)发生的角度阐述KD所引发的全身性变化,通过调控离子通道的开放和关闭,调节兴奋性和抑制性神经递质的平衡,增加能量代谢、减少氧自由基的生成和促进神经细胞再生等方式发挥抗癫疒间作用.%Ketogenic diet (KD) is a high-fat,low-protein,low-carbohydrate diet that results in series of adaptive changes such as ketosis,fatty acid increasing and glycolysis depression.The mechanisms of the epilepsy correlated with the iron channel,neurotransmitter and neurocyte injury.The novel stresses the antiepileptic effects of above general changes in controlling the iron channels open or close,balancing the excitable and inhibitive neurotransmitters,increasing energy reserve,inhibiting free radical production and promoting neurocyte regeneration.

  9. Orphan drugs

    Directory of Open Access Journals (Sweden)

    Goločorbin-Kon Svetlana

    2013-01-01

    Full Text Available 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 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. Conclusion. 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. [Projekat Ministarstva nauke Republike Srbije, br. III 41012

  10. Study Drugs

    Science.gov (United States)

    ... messages back and forth by releasing chemicals called neurotransmitters. Prescription stimulants have chemical structures that are similar to some neurotransmitters. When someone takes them, the drugs boost the ...

  11. 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.

  12. Pharmacokinetics and drug interactions of eslicarbazepine acetate.

    Science.gov (United States)

    Bialer, Meir; Soares-da-Silva, Patricio

    2012-06-01

    Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life (t(1/2,eff) ) of eslicarbazepine was 20-24 h, which is approximately two times longer than its terminal half-life (t(1/2)). At clinically relevant doses (400-1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral contraceptive and simvastatin. PMID:22612290

  13. Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice

    Institute of Scientific and Technical Information of China (English)

    Abrar M Tamboli; Rukhsana A Rub; Pinaki Ghosh; SL Bodhankar

    2012-01-01

    Objective:To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models. Methods:The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison. Results:Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P<0.050–0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model. Conclusions:In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.

  14. Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease.

    Science.gov (United States)

    Xiao, Rong

    2016-01-01

    Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD.

  15. Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in an Adolescent Treated With Lamotrigine.

    Science.gov (United States)

    Ginory, Almari; Chaney-Catchpole, Michelle; Demetree, Julie M; Mayol Sabatier, Laura M; Nguyen, Mathew

    2013-07-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity syndrome most commonly associated with antiepileptic agents, allopurinol, and sulfonamides. It is a severe adverse reaction associated with fever, rash, eosinophilia, lymphadenopathy, and internal organ involvement. We present the case of a 17-year-old Caucasian female with bipolar disorder type II and posttraumatic stress disorder treated with lamotrigine for a non-Food and Drug Administration-approved indication that developed DRESS syndrome at an initial dose higher than that recommended. Her symptoms were atypical in that she developed a rash with influenza-like symptoms that resolved after discontinuation of lamotrigine and returned 8 days later. She was hospitalized because of elevated liver enzymes and treated with corticosteroids. In patients presenting with rash and systemic symptoms, DRESS syndrome should be considered and treated appropriately to reduce mortality, which can be as high as 10%. Treatment includes withdrawal of the offending agent and corticosteroids. PMID:24052787

  16. Drug Interactions

    Science.gov (United States)

    ... WITH HIV MEDICATIONS? Protease inhibitors and non-nucleoside reverse transcriptase inhibitors are processed by the liver and cause many ... taken with any protease inhibitor or non-nucleoside reverse transcriptase inhibitor. You can also check for drug-drug and ...

  17. Drug treatment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010263 Drug resistance mechanism of non-small cell lung cancer PC9/AB2 cell line with acquired drug resistance to gefitinib.JU Lixia(鞠立霞),et al. Dept Oncol,Shanghai Pulm Hosp,Tongji Univ,Shanghai 200433. Chin J Tuberc Respir Dis 2010;33(5):354-358. Objective To

  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. Concurrency revisited: increasing and compelling epidemiological evidence

    Directory of Open Access Journals (Sweden)

    Mah Timothy L

    2011-06-01

    Full Text Available Abstract Multiple sexual partnerships must necessarily lie at the root of a sexually transmitted epidemic. However, that overlapping or concurrent partnerships have played a pivotal role in the generalized epidemics of sub-Saharan Africa has been challenged. Much of the original proposition that concurrent partnerships play such a role focused on modelling, self-reported sexual behaviour data and ethnographic data. While each of these has definite merit, each also has had methodological limitations. Actually, more recent cross-national sexual behaviour data and improved modelling have strengthened these lines of evidence. However, heretofore the epidemiologic evidence has not been systematically brought to bear. Though assessing the epidemiologic evidence regarding concurrency has its challenges, a careful examination, especially of those studies that have assessed HIV incidence, clearly indicates a key role for concurrency. Such evidence includes: 1 the early and dramatic rise of HIV infection in generalized epidemics that can only arise from transmission through rapid sequential acute infections and thereby concurrency; 2 clear evidence from incidence studies that a major portion of transmission in the population occurs via concurrency both for concordant negative and discordant couples; 3 elevation in risk associated with partner's multiple partnering; 4 declines in HIV associated with declines in concurrency; 5 bursts and clustering of incident infections that indicate concurrency and acute infection play a key role in the propagation of epidemics; and 6 a lack of other plausible explanations, including serial monogamy and non-sexual transmission. While other factors, such as sexually transmitted infections, other infectious diseases, biological factors and HIV sub-type, likely play a role in enhancing transmission, it appears most plausible that these would amplify the role of concurrency rather than alter it. Additionally, critics of concurrency have not proposed plausible alternative explanations for why the explosive generalized epidemics occurred. Specific behaviour change messaging bringing the concepts of multiple partnering and concurrency together appears salient and valid in promoting safer individual behaviour and positive social norms.

  2. Compelled to do the right thing

    CERN Document Server

    Laguna, M F; Iglesias, J R

    2012-01-01

    We use a model of opinion formation to study the consequences of some mechanisms attempting to enforce the right behaviour in a society. We start from a model where the possible choices are not equivalent (such is the case when the agents decide to comply or not with a law) and where an imitation mechanism allow the agents to change their behaviour based on the influence of a group of partners. In addition, we consider the existence of two social constraints: a) an external authority, called monitor, that imposes the correct behaviour with infinite persuasion and b) an educated group of agents that act upon their fellows but never change their own opinion, i.e., they exhibit infinite adamancy. We determine the minimum number of monitors to induce an effective change in the behaviour of the social group, and the size of the educated group that produces the same effect. Also, we compare the results for the cases of random social interactions and agents placed on a network. We have verified that a small number o...

  3. Compelled to do the right thing

    Science.gov (United States)

    Fabiana Laguna, M.; Abramson, Guillermo; Iglesias, J. Roberto

    2013-05-01

    We use a model of opinion formation to study the consequences of some mechanisms attempting to enforce the right behaviour in a society. We start from a model where the possible choices are not equivalent (such is the case when the agents decide to comply or not with a law) and where an imitation mechanism allow the agents to change their behaviour based on the influence of a group of partners. In addition, we consider the existence of two social constraints: (a) an external authority, called monitor, that imposes the correct behaviour with infinite persuasion and (b) an educated group of agents that act upon their fellows but never change their own opinion, i.e., they exhibit infinite adamancy. We determine the minimum number of monitors to induce an effective change in the behaviour of the social group, and the size of the educated group that produces the same effect. Also, we compare the results for the cases of random social interactions and agents placed on a network. We have verified that a small number of monitors are enough to change the behaviour of the society. This also happens with a relatively small educated group in the case of random interactions.

  4. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    International Nuclear Information System (INIS)

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  5. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Valeria A.; Escandar, Graciela M., E-mail: escandar@iquir-conicet.gov.ar

    2013-06-11

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  6. Drug eruptions: An 8-year study including 106 inpatients at a dermatology clinic in Turkey

    Directory of Open Access Journals (Sweden)

    Fatma Akpinar

    2012-01-01

    Full Text Available Background: Few clinical studies are found in the literature about patients hospitalized with a diagnosis of cutaneous drug eruption. Aims: To determine the clinical types of drug eruptions and their causative agents in a hospital-based population. Materials and Methods: This retrospective study was performed in the Dermatology Department of Haseki General Hospital. Through 1751 patients hospitalized in this department between 2002 and 2009, inpatients diagnosed as drug eruption were evaluated according to WHO causality definitions. 106 patients composed of probable and possible cases of cutaneous drug eruptions were included in this study. Results: Seventy one females and 35 males were evolved. Mean age was 44.03±15.14. Duration between drug intake and onset of reaction varied from 5 minutes to 3 months. The most common clinical type was urticaria and/or angioedema in 48.1% of the patients, followed by maculopapular rash in 13.2%, and drug rash with eosinophilia and systemic symptoms in 8.5%. Drugs most frequently associated with cutaneous drug eruptions were antimicrobial agents in 40.5% of the patients, followed by antipyretic/anti-inflammatory analgesics in 31.1%, and antiepileptics in 11.3%. Conclusion: Urticaria and/or angioedema and maculopapular rash comprised majority of the drug eruptions. Rare reactions such as acute generalized exanthematous pustulosis, sweet syndrome, oral ulceration were also found. Antimicrobial agents and antipyretic/anti-inflammatory analgesics were the most commonly implicated drugs. Infrequently reported adverse reactions to myorelaxant agents, newer cephalosporins and fluoroquinolones were also detected. We suppose that studies on drug eruptions should continue, because the pattern of consumption of drugs is changing in every country at different periods and many new drugs are introduced on the market continuously.

  7. 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. PMID:27470339

  8. 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 ...

  9. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  10. Drug Facts

    Medline Plus

    Full Text Available ... Websites Search Share Listen English Español Information about this page Click on the button that says "Listen" ... the computer will read the text to you. This web site talks about drug abuse, addiction and ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... computer will read the text to you. This web site talks about drug abuse, addiction and treatment. ... of the U.S. Department of Health and Human Services . PDF documents require the free Adobe Reader . Microsoft ...

  12. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  13. Club Drugs

    Science.gov (United States)

    ... following information: Facts and Figures – Includes the latest information and statistics. Legislation – A sample of links to online Federal and ... recognized agencies and organizations that provide services or information. CLUB DRUGS Summary Facts & ... & Technical Assistance Grants & Funding Related ...

  14. 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 - ...

  15. Herbal drugs and drug interactions

    Directory of Open Access Journals (Sweden)

    Gül Dülger

    2012-01-01

    Full Text Available Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions of some most commanly used herbals (St John's wort, ginkgo biloba, ginseng, ginger, garlic, echinacea, ephedra and valerian with the conventional drugs were reviewed. Pharmacokinetic interactions involve mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoproteins by the herbal medicine, thus changing the absorption and/or elimination rate and consequently the efficacy of the concommitantly used drugs. St John's wort, a well known enzyme inducer, decreases the efficacy of most of the other drugs that are known to be the substrates of these enzymes.Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

  16. Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

    OpenAIRE

    Dina Indrati; Herry Prasetyo

    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...

  17. 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!

  18. 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.

  19. Drug Allergy.

    Science.gov (United States)

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  20. Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects.

    Science.gov (United States)

    Convertino, Irma; Sansone, Alice Capogrosso; Marino, Alessandra; Galiulo, Maria T; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado; Tuccori, Marco

    2016-10-01

    Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about

  1. Effects of Drug Abuse

    Science.gov (United States)

    ... Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking ...

  2. Other Drugs of Abuse

    Science.gov (United States)

    ... Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking ...

  3. 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) | ...

  4. 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 ( ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help ... her life. She finds support from family and friends who don't use marijuana. Haga clic aquí ...

  6. Antineoplastic Drugs.

    Science.gov (United States)

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  7. Drugged Driving

    Science.gov (United States)

    ... View All NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home Site Map FAQs Accessibility Privacy FOIA(NIH) Working at NIDA Contact Subscribe Archives PDF documents require the free Adobe Reader . Microsoft Word documents require the free Microsoft Word ...

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

    Directory of Open Access Journals (Sweden)

    Francesca Pizzo

    2013-12-01

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

  9. 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.

  10. Drug Rash (Unclassified Drug Eruption) in Children

    Science.gov (United States)

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  11. 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...

  12. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  13. AIDSinfo Drug Database

    Science.gov (United States)

    ... Widgets Order Publications Skip Nav AIDS info Drug Database Home > Drugs Español small medium large Text Size ... health care providers and patients. Search the Drug Database Help × Search by drug name Performs a search ...

  14. Urine drug screen

    Science.gov (United States)

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

  15. Teenagers and drugs

    Science.gov (United States)

    ... and drugs; Symptoms of drug use in teenagers; Drug abuse - teenagers; Substance abuse - teenagers ... for a specialist who has experience working with teenagers. DO NOT ... drug abuse . You can find more information at teens.drugabuse. ...

  16. 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.

  17. 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.

  18. 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...

  19. Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Pierangelo eCifelli

    2013-07-01

    Full Text Available The pharmacological treatment of mesial temporal lobe epilepsy (mTLE, the most common epileptic syndrome in adults, is still unsatisfactory, as one third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown of the evoked currents (IGABA, which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam and on the neurotrophin BDNF, which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, levetiracetam did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of levetiracetam was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome.

  20. Drug reaction with eosinophilia and systemic symptoms syndrome in a patient taking phenytoin and levetiracetam: a case report

    Directory of Open Access Journals (Sweden)

    Hall David Jeffrey

    2013-01-01

    Full Text Available Abstract Introduction Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening hypersensitivity reaction with rash, fever, and internal organ involvement, often hepatitis, occurring most commonly two to eight weeks after initiation of a medication. The present case is an example of severe and potentially life-threatening hepatitis as a manifestation of drug reaction with eosinophilia and systemic symptoms syndrome. Case presentation We report a case of anti-epileptic-induced drug reaction with eosinophilia and systemic symptoms syndrome in an 18-year-old African-American man who presented with a five-day history of rash, periorbital and upper extremity edema, hepatitis and fever. Laboratory findings revealed an atypical lymphocytosis, eosinophilia, and elevated serum transaminases. No drug allergies were reported at the time of presentation, but phenytoin and levetiracetam therapy had been initiated five weeks prior to hospital admission for new-onset seizures. Both medications were discontinued on hospital admission, and after three days of high-dose corticosteroid therapy the patient experienced resolution of both his symptoms and laboratory markers of inflammation. Conclusion Given the significant mortality attributed to drug reaction with eosinophilia and systemic symptoms syndrome, medical personnel should be aware of the potential for this severe hypersensitivity reaction and should ensure close follow-up and offer anticipatory guidance when beginning any new medication, particularly anti-epileptic therapy. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and initiation of appropriate therapy are imperative in limiting morbidity.

  1. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

    Directory of Open Access Journals (Sweden)

    Dini Gabriele

    2004-10-01

    Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

  2. Drug abuse

    International Nuclear Information System (INIS)

    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

  3. Drug-drug interactions in the hospital

    OpenAIRE

    Vonbach, Priska

    2007-01-01

    Introduction Drug interaction screening programs are an important tool to check prescriptions of multiple drugs for potential drug-drug interactions (pDDIs). Several programs are available on the market. They differ in layout, update frequency, search functions, content and price. The aim of the current study was to critically appraise several interaction screening programs in the Department of Medicine of a Swiss public teaching hospital. Methods A drug interaction screening program had to f...

  4. Mozart's music in children with drug-refractory epileptic encephalopathies.

    Science.gov (United States)

    Coppola, Giangennaro; Toro, Annacarmela; Operto, Francesca Felicia; Ferrarioli, Giuseppe; Pisano, Simone; Viggiano, Andrea; Verrotti, Alberto

    2015-09-01

    Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozart's compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozart's compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior. PMID:26093514

  5. [Drug treatment and interventional pain therapy in back pain patients].

    Science.gov (United States)

    Sprott, Haiko; Klauke, Wolfgang

    2013-09-01

    The treatment of chronic, non-malignant low-back pain is based on the patients' history and the clinical examination. It can be assumed that half of the cases present with a neuropathic pain component which needs to be treated with antidepressive and antiepileptic drugs instead of "pure" analgesics. Opioids should be considered with extreme caution because of their toxicity. Chronic non-malignant back pain is the prototype for interdisciplinary treatment approaches and multi-modal interdisciplinary settings, including pain programmes. However, a personalised strategy has to be preferred in most cases. A quick relief of pain is important in order to improve function as well as to re-integrate the patient into professional life. Spinal infiltrations can be of both diagnostic as well as therapeutic benefits. Their indication must be considered carefully, especially if the invasive diagnostic intervention has no therapeutic consequences. The interventional procedures should only be used as part of a multimodal approach in patients without any psychological problem. The sole use of interventions supports the purely somatic orientation of many patients and thus leads us in the wrong direction.

  6. Neuropeptides as targets for the development of anticonvulsant drugs.

    Science.gov (United States)

    Clynen, Elke; Swijsen, Ann; Raijmakers, Marjolein; Hoogland, Govert; Rigo, Jean-Michel

    2014-10-01

    Epilepsy is a common neurological disorder characterized by recurrent seizures. These seizures are due to abnormal excessive and synchronous neuronal activity in the brain caused by a disruption of the delicate balance between excitation and inhibition. Neuropeptides can contribute to such misbalance by modulating the effect of classical excitatory and inhibitory neurotransmitters. In this review, we discuss 21 different neuropeptides that have been linked to seizure disorders. These neuropeptides show an aberrant expression and/or release in animal seizure models and/or epilepsy patients. Many of these endogenous peptides, like adrenocorticotropic hormone, angiotensin, cholecystokinin, cortistatin, dynorphin, galanin, ghrelin, neuropeptide Y, neurotensin, somatostatin, and thyrotropin-releasing hormone, are able to suppress seizures in the brain. Other neuropeptides, such as arginine-vasopressine peptide, corticotropin-releasing hormone, enkephalin, β-endorphin, pituitary adenylate cyclase-activating polypeptide, and tachykinins have proconvulsive properties. For oxytocin and melanin-concentrating hormone both pro- and anticonvulsive effects have been reported, and this seems to be dose or time dependent. All these neuropeptides and their receptors are interesting targets for the development of new antiepileptic drugs. Other neuropeptides such as nesfatin-1 and vasoactive intestinal peptide have been less studied in this field; however, as nesfatin-1 levels change over the course of epilepsy, this can be considered as an interesting marker to diagnose patients who have suffered a recent epileptic seizure.

  7. 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)…

  8. Drugs and lactation

    International Nuclear Information System (INIS)

    Different kinds of drugs who can be transferred through the mother's milk to the lactant and its effects are showed in this work. A list of them as below: cardiotonics, diuretics, anti-hypertensives, beta-blockings, anti-arrythmics, drugs with gastrintestinal tract action, hormones, antibiotics and chemotherapeutics, citostatic drugs, central nervous system action drugs and anticoagulants drugs. (L.M.J.)

  9. [Drug-drug interactions in antirheumatic treatment].

    Science.gov (United States)

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  10. Drugs and drug policy in the Netherlands

    OpenAIRE

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against illegal trafficking in hard drugs. This multifaceted approach established the basic principles and operating practices of contemporary social and criminal drug policy in the Netherlands.

  11. [Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

    Science.gov (United States)

    Jóźwiak, Sergiusz

    2007-01-01

    Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy.

  12. Drug: D06717 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0 Crude drugs D06717 Safflower (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs... for removing blood stasis D06717 *Safflower; Safflower Drugs for external use Drugs

  13. Drug: D06912 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs for removing blood stasis D06912 *Quercus cortex; Bokusoku Drug...s for external use Drugs for external use D06912 *Quercu

  14. Attitudes towards drug legalization among drug users.

    Science.gov (United States)

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  15. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  16. Drugs Approved for Leukemia

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  17. Prescription Drug Abuse

    Science.gov (United States)

    ... a drug abuser aggressive or paranoid. Although stimulant abuse might not lead to physical dependence and withdrawal, the feelings these drugs give people can cause them to use the drugs more and more ...

  18. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  19. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  20. Drug-induced hepatitis

    Science.gov (United States)

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  1. Drug Development Process

    Science.gov (United States)

    ... Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Step 1 Discovery and Development Discovery and Development Research for a new drug ...

  2. 高效液相色谱法同时测定四种抗癫痫药物的血药浓度%Simultaneous determination of the plasma concentration in four antiepileptic drugs using high performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    盛高峰; 詹少卿

    2014-01-01

    目的 建立用HPLC同时测定血清中多种抗癫痫药物卡马西平(carbamazepine,CBZ)、苯巴比妥(phenobarbital,PB)、硝西泮(nitrazepam,NTZ)、氯硝西泮(clonazepam,CNZ)等的方法. 方法 用一定方法处理血清样本,色谱柱为Nova-pak C18柱(150 mm ×3.9 mm,4μm);流动相为0.01 mol/L磷酸二氢钾缓冲液(pH 2.15)-乙腈(29∶71,V/V),监测波长223 nm;流速1 ml/min,柱温30℃. 结果 样品血清经处理,所留杂质不干扰被检测药品.在该色谱条件下以上药物能良好分离,在0.01-10 mg/L范围浓度与峰面积呈良好的线性关系(r>0.999 0),方法回收率均大于90%,日内、日间RSD均小于10%.结论 该方法快速、准确、简便、实用,适用于以上治疗药物的治疗监测.

  3. 癫痫过程及药物治疗对生长激素分泌的影响%Effect of seizures and antiepileptic drugs on growth hormone secretions

    Institute of Scientific and Technical Information of China (English)

    王明芳; 毛向辉

    2003-01-01

    目的:探讨癫痫发作和抗癫痫药物治疗对GH分泌的影响.方法:利用RIA法测定88例癫痫患者癫痫发作前后和110例用不同AEDs治疗和21例未用AEDs的癫痫患者血清中GH的水平.结果:癫痫发作后GH分泌明显升高,发作后30min有57例病人GH分泌达到峰值,是基础GH水平的4倍,发作后90min,有89.8%的病例的GH水平下降,其中有53例GH水平下降至正常值范围,癫痫发作后血清GH水平的变化与癫痫病灶位置无关,发作后均可引起GH水平的升高;SFI越短,基础GH水平越低,发作后GH的峰值越低;在AEDs治疗组和纯中医药治疗组中,GH水平与癫痫对照组无明显差异,而且所有病人的GH基础水平比正常对照低.结论:癫痫过程影响GH分泌,使基础GH水平减低.AEDs单一治疗和联合治疗不明显影响血清GH水平.结果揭示由于长期的反复发作,垂体GH的储备下降或耗竭,引起GH的脉冲分泌量减少,从而导致基础GH水平低于正常.

  4. Antiepileptic Drugs as a Possible Neuroprotective Strategy in Brain Ischemia%抗癫(癎)药--脑缺血时的一种可能的神经保护策略

    Institute of Scientific and Technical Information of China (English)

    Paolo Calabresi; Letizia M. Cupini; Diego Centonze; Francesco Pisani; Giorgio Bernardi; 李继英; 承颖亮

    2004-01-01

    最近,已有一些新的抗癫(癎)药(AED)用于临床.同传统AED的作用一样,这些新的AED作用于突触前和突触后的多个细胞位点.应用AED进行药物治疗的主要共同目标是通过减少兴奋传递或增强神经元抑制来抵消异常的脑兴奋性.有趣的是,脑缺血时也会出现兴奋性氨基酸的过度释放和神经元抑制的减弱.因此,作为一种可能的脑缺血神经保护策略,最近AED的应用正受到越来越多的关注.许多AED已经在卒中动物模型中进行过实验,并取得了令人鼓舞的结果.利用啮齿动物全脑或局灶性缺血模型进行的实验研究,已使人们对各种AED可能的神经保护作用有所了解.但是,对人急性卒中的治疗,这些研究的含义却并非总是那么显而易见.事实上,应用多种针对大多数AED调控的同一电压和配体门控通道的药物进行的各种临床研究均未显示出神经保护作用.在实验性动物模型与人类卒中方面,局灶性缺血性损伤形成的机制不同,还需要进一步研究,以展示一种新的在将来可用于神经保护的治疗远景.

  5. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    Directory of Open Access Journals (Sweden)

    Chandra Prakash

    2015-12-01

    Full Text Available Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs, and transport proteins coordinate drug influx (phase 0 and drug/drug-metabolite efflux (phase III. Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs, i.e. PXR (pregnane X receptor and CAR (constitutive androstane receptor, and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR, due to transactivation of xenobiotic-response elements (XREs present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug's impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse

  6. 治疗药物监测的研究进展%The research progress in therapeutic drug monitoring

    Institute of Scientific and Technical Information of China (English)

    谢吉科; 姜德春

    2011-01-01

    本文对治疗药物监测的药物如中药、抗癫痫药、免疫抑制药、抗逆转录病毒药物、抗精神病药物、抗肿瘤药物和抗微生物药物的最新研究进展进行综述,介绍其方法学上的最新进展,如利用液质联用将成为发展方向.结合群体药动学和药物遗传学的最新发展,研究疾病药物治疗中的新方法,指导临床个体化用药,提出治疗药物监测(TDM)新的发展方向,如利用基因分型和基因芯片对患者测定基因型,以指导临床合理用药.%In this article, the recent progresses on therapeutic drug monitoring which involves those drugs such as traditional Chinese medicine, antiepileptic drugs, immunosuppressive drugs, antiretroviral drugs, antipsychotic drugs, antitumor drugs and anti-microbial drugs were reviewed. The latest development of methodology was described, and the use of LC-MS will be the development direction. Combined with the latest developments of population pharmacokinetic and pharmacogenetic, new methods for individualized medicine were developed, and new development directions for therapeutic drug monitoring were proposed, such as use of genotyping and gene chips to identify the genotype for personalized medicine.

  7. Drug: D06770 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ommia family) Eucommia bark (dried) Major component: Gutta-percha Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs... and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D0...e Drugs Drugs for Qi Drugs for replenishing Qi D06770 Eucommia bark Crude drugs [BR:br08305] Dicot plants: a

  8. Intrathecal drug administration in chronic pain syndromes.

    Science.gov (United States)

    Ver Donck, Ann; Vranken, Jan H; Puylaert, Martine; Hayek, Salim; Mekhail, Nagy; Van Zundert, Jan

    2014-06-01

    Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long-term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo-controlled trials. A randomized study showed this treatment option to be effective over a short follow-up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drug administration in patients suffering from cancer-related pain is more compelling than that of chronic noncancer pain. PMID:24118774

  9. Managing drug-resistant epilepsy: challenges and solutions

    Science.gov (United States)

    Dalic, Linda; Cook, Mark J

    2016-01-01

    Despite the development of new antiepileptic drugs (AEDs), ~20%–30% of people with epilepsy remain refractory to treatment and are said to have drug-resistant epilepsy (DRE). This multifaceted condition comprises intractable seizures, neurobiochemical changes, cognitive decline, and psychosocial dysfunction. An ongoing challenge to both researchers and clinicians alike, DRE management is complicated by the heterogeneity among this patient group. The underlying mechanism of DRE is not completely understood. Many hypotheses exist, and relate to both the intrinsic characteristics of the particular epilepsy (associated syndrome/lesion, initial response to AED, and the number and type of seizures prior to diagnosis) and other pharmacological mechanisms of resistance. The four current hypotheses behind pharmacological resistance are the “transporter”, “target”, “network”, and “intrinsic severity” hypotheses, and these are reviewed in this paper. Of equal challenge is managing patients with DRE, and this requires a multidisciplinary approach, involving physicians, surgeons, psychiatrists, neuropsychologists, pharmacists, dietitians, and specialist nurses. Attention to comorbid psychiatric and other diseases is paramount, given the higher prevalence in this cohort and associated poorer health outcomes. Treatment options need to consider the economic burden to the patient and the likelihood of AED compliance and tolerability. Most importantly, higher mortality rates, due to comorbidities, suicide, and sudden death, emphasize the importance of seizure control in reducing this risk. Overall, resective surgery offers the best rates of seizure control. It is not an option for all patients, and there is often a significant delay in referring to epilepsy surgery centers. Optimization of AEDs, identification and treatment of comorbidities, patient education to promote adherence to treatment, and avoidance of triggers should be periodically performed until further

  10. Young drug addicts and the drug scene.

    Science.gov (United States)

    Lucchini, R

    1985-01-01

    The drug scene generally comprises the following four distinct categories of young people: neophytes, addicts who enjoy a high status vis-à-vis other addicts, multiple drug addicts, and non-addicted drug dealers. It has its own evolution, hierarchy, structure and criteria of success and failure. The members are required to conform to the established criteria. The integration of the young addict into the drug scene is not voluntary in the real sense of the word, for he is caught between the culture that he rejects and the pseudo-culture of the drug scene. To be accepted into the drug scene, the neophyte must furnish proof of his reliability, which often includes certain forms of criminal activities. The addict who has achieved a position of importance in the drug world serves as a role model for behaviour to the neophyte. In a more advanced phase of addiction, the personality of the addict and the social functions of the drug scene are overwhelmed by the psychoactive effects of the drug, and this process results in the social withdrawal of the addict. The life-style of addicts and the subculture they develop are largely influenced by the type of drug consumed. For example, it is possible to speak of a heroin subculture and a cocaine subculture. In time, every drug scene deteriorates so that it becomes fragmented into small groups, which is often caused by legal interventions or a massive influx of new addicts. The fragmentation of the drug scene is followed by an increase in multiple drug abuse, which often aggravates the medical and social problems of drug addicts. PMID:4075000

  11. Molecular Genetics of Drug-resistance in Epilepsies

    Directory of Open Access Journals (Sweden)

    Kurupath Radhakrishnan

    2015-06-01

    Full Text Available Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to antiepileptic drugs (AEDs, etiopathogenesis of which is poorly understood. The genes encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein [ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1, ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7], and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense investigation to unravel the mysteries of AED-resistance. However, till today, a consistent and reliable result that could help the clinician either to predict drug resistance or to overcome it has not been forthcoming. The discrepant results may be related to variations in the definition of drug-resistance, heterogeneous patient populations, ethnic variations in the frequency distribution of single nucleotide polymorphisms (SNPs and the selection of SNPs. Understanding of these limitations of existing studies, hopefully, will help in designing better studies. Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive toantiepileptic drugs (AEDs, etiopathogenesis of which is poorly understood. The genesencoding the proteins that regulate the pharmacokinetics such as P-glycoprotein[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABAreceptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intenseinvestigation to unravel the mysteries of AED-resistance. However, till today, aconsistent and reliable result that could help the clinician either to predict drugresistanceor to overcome it has not been forthcoming. The discrepant results may berelated to variations in the definition of drug-resistance, heterogeneous patientpopulations, ethnic

  12. Drugs and Young People

    Science.gov (United States)

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  13. Hsp90 governs dispersion and drug resistance of fungal biofilms.

    Directory of Open Access Journals (Sweden)

    Nicole Robbins

    2011-09-01

    Full Text Available Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving

  14. Food and drugs

    Directory of Open Access Journals (Sweden)

    Đaković-Švajcer Kornelija

    2002-01-01

    Full Text Available Food can exert a significant influence on the effects of certain drugs. The interactions between food and drugs can be pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions most often take place on absorption and drug metabolism levels. Absorption can be either accelerated or delayed, increased or decreased, while drug metabolism can be either stimulated or inhibited. The factors which influence food-drug interactions are as follows: composition and physic-chemical properties of drugs, the interval between a meal and drug intake and food composition. Food consistency is of lesser influence on drug bioavailability than food composition (proteins, fats, carbohydrates, cereals. Important interactions can occur during application of drugs with low therapeutic index, whereby the plasma level significantly varies due to changes in resorption or metabolism (e.g. digoxin, theophyllin, cyclosporin and drugs such as antibiotics, whose proper therapeutic effect requires precise plasma concentrations.

  15. Sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the CPRD primary care database

    Science.gov (United States)

    Fairhurst, Caroline; Martin, Fabiola; Watt, Ian; Doran, Tim; Bland, Martin

    2016-01-01

    Introduction Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. VGSCs are also widely expressed in various cancers, including those of the breast, bowel and prostate. A number of VGSC-inhibiting drugs have been shown to inhibit cancer cell proliferation, invasion, tumour growth and metastasis in preclinical models, suggesting that VGSCs may be novel molecular targets for cancer treatment. Surprisingly, we previously found that prior exposure to VGSC-inhibiting drugs may be associated with reduced overall survival in patients with cancer, but we were unable to control for the cause of death or indication for prescription. The purpose of the present study is to interrogate a different database to further investigate the relationship between VGSC-inhibiting drugs and cancer-specific survival. Methods and analysis A cohort study using primary care data from the Clinical Practice Research Datalink database will include patients with diagnosis of breast, bowel and prostate cancer (13 000). The primary outcome will be cancer-specific survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare survival of patients taking VGSC-inhibiting drugs (including antiepileptic drugs and class I antiarrhythmic agents) with patients with cancer not taking these drugs, adjusting for cancer type, age and sex. Drug exposure will be treated as a time-varying covariate to account for potential immortal time bias. Various sensitivity and secondary analyses will be performed. Ethics and dissemination The project has been reviewed and approved by the University of York Ethical Review Process. Results will be presented at an international conference and published in open access peer-reviewed journals according to the STROBE and RECORD guidelines. PMID:27601493

  16. Practice Gaps: Drug Reactions.

    Science.gov (United States)

    Wolverton, Stephen E

    2016-07-01

    The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions. PMID:27363888

  17. Drug: D06742 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Crude drugs D06742 Houttuynia herb (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for clearing heat Drug...s for clearing heat D06742 *Houttuynia herb; Houttuynia harb Drugs... for pus discharge Drugs for pus discharge D06742 *Houttuynia herb; Houttuynia harb Crude drugs [B

  18. Monitoring of drug-drug and drug-food interactions.

    Science.gov (United States)

    Garabedian-Ruffalo, S M; Syrja-Farber, M; Lanius, P M; Plucinski, A

    1988-07-01

    A program for detecting and preventing potentially serious drug-drug and drug-food interactions is described. Two clinical pharmacists developed drug interaction alert (DIA) cards for each potential interaction to be monitored. The cards contain information about the proposed mechanism and potential result of the interaction, as well as information about how to monitor or circumvent the interaction. Staff pharmacists check for the occurrence of potential interactions daily as they verify the filling of the patient-medication cassettes; a poster of all the interactions that are included in the program is posted in each satellite pharmacy to serve as a quick reference for the pharmacists. When a pharmacist detects a potential interaction, he or she completes a DIA card and places it in the medication cassette drawer (if the notice is directed to the nurse) or on the front of the patient's chart (if the notice is directed to the physician). The program was introduced to hospital personnel through inservice education programs and departmental newsletters. The results of a quality assurance review indicated that 95 of 279 (34%) cards dispensed to nurses and 40 of 49 (82%) cards dispensed to physicians resulted in some form of action. The program to detect and prevent potentially serious drug-drug and drug-food interactions has been successful. PMID:3414718

  19. Drug: D06749 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available drugs 5100 Crude drugs D06749 Nuphar rhizome (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs... for blood Drugs for removing blood stasis D06749 Nuphar rhizome; Nup

  20. Drug: D05431 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (NF) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Diaphoretic d...rugs Diaphoretic drugs pungent in flavor and cool in property D05431 *Peppermint; Peppermint Drugs for external use Drugs

  1. Drug: D09185 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Stomachic and antidiarrheal drugs Stomachic ...and antidiarrheal drugs D09185 *Myrica Drugs for external use Drugs for external use D09185 *Myrica Crude dr

  2. Drug: D03404 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available drugs D03404 Cardamon (JP16); Cardamom seed (NF) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs... for dampness Drugs for resolving dampness D03404 Cardamon; Cardamom seed; Cardamon Crude drugs [B

  3. Drug: D06767 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available gs D06767 Benincasa seed (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs... for removing blood stasis D06767 *Benincasa seed Drugs for pus discharge Drugs

  4. Drug: D06772 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Stomachic an...d antidiarrheal drugs Stomachic and antidiarrheal drugs D06772 *Ginseng; Powdered ginseng; Ginseng Drugs for Qi Drugs

  5. Drug: D06803 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 10 Crude drugs 5100 Crude drugs D06803 Nelumbo seed (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs... for Qi Drugs for replenishing Qi D06803 Nelumbo seed Crude dr

  6. Drug: D06894 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available daisy family) Artemisia leaf (dried) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs... for replenishing blood D06894 *Artemisiae folium; Gaiyo Drugs for external use Drugs

  7. Drug: D06813 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nent: Scopoletin [CPD:C01752] Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Stomachic and a...ntidiarrheal drugs Stomachic and antidiarrheal drugs D06813 *Dolichos seed Drugs for dampness Drugs

  8. Drug: D09151 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available raditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for Qi Drugs for regulating Qi D09151 Sw...eetflag rhizome Other drugs Drugs for resuscitation D09151 Acorus gramineus rhizo

  9. Drug: D04705 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 05 Lithospermum root (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs... for clearing heat Drugs for clearing heat D04705 *Lithospermum root; Lithospermum root Drugs for external use Drugs

  10. Drug: D06736 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ehmannia root (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for replenishing Ying Drugs... for replenishing Ying D06736 *Rehmannia root; Rehmannia root Drugs for blood Drugs for replenishin

  11. Treatment Approaches for Drug Addiction

    Science.gov (United States)

    ... for Drug Addiction DrugFacts: Treatment Approaches for Drug Addiction Email Facebook Twitter Revised July 2016 NOTE: This ... treatment options in your state. What is drug addiction? Drug addiction is a chronic disease characterized by ...

  12. Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy

    Science.gov (United States)

    Balestrini, Simona; Clayton, Lisa M S; Bartmann, Ana P; Chinthapalli, Krishna; Novy, Jan; Coppola, Antonietta; Wandschneider, Britta; Stern, William M; Acheson, James; Bell, Gail S; Sander, Josemir W; Sisodiya, Sanjay M

    2016-01-01

    Objective Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter ‘integrity’. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. Methods Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. Results The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient −0.16, p=0.004) and presence of intellectual disability (coefficient −4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. Conclusions Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings. PMID:25886782

  13. Best practices for the use of itraconazole as a replacement for ketoconazole in drug-drug interaction studies.

    Science.gov (United States)

    Liu, Lichuan; Bello, Akintunde; Dresser, Mark J; Heald, Donald; Komjathy, Steven Ferenc; O'Mara, Edward; Rogge, Mark; Stoch, S Aubrey; Robertson, Sarah M

    2016-02-01

    Ketoconazole has been widely used as a strong cytochrome P450 (CYP) 3A (CYP3A) inhibitor in drug-drug interaction (DDI) studies. However, the US Food and Drug Administration has recommended limiting the use of ketoconazole to cases in which no alternative therapies exist, and the European Medicines Agency has recommended the suspension of its marketing authorizations because of the potential for serious safety concerns. In this review, the Innovation and Quality in Pharmaceutical Development's Clinical Pharmacology Leadership Group (CPLG) provides a compelling rationale for the use of itraconazole as a replacement for ketoconazole in clinical DDI studies and provides recommendations on the best practices for the use of itraconazole in such studies. Various factors considered in the recommendations include the choice of itraconazole dosage form, administration in the fasted or fed state, the dose and duration of itraconazole administration, the timing of substrate and itraconazole coadministration, and measurement of itraconazole and metabolite plasma concentrations, among others. The CPLG's recommendations are based on careful review of available literature and internal industry experiences. PMID:26044116

  14. Best practices for the use of itraconazole as a replacement for ketoconazole in drug-drug interaction studies.

    Science.gov (United States)

    Liu, Lichuan; Bello, Akintunde; Dresser, Mark J; Heald, Donald; Komjathy, Steven Ferenc; O'Mara, Edward; Rogge, Mark; Stoch, S Aubrey; Robertson, Sarah M

    2016-02-01

    Ketoconazole has been widely used as a strong cytochrome P450 (CYP) 3A (CYP3A) inhibitor in drug-drug interaction (DDI) studies. However, the US Food and Drug Administration has recommended limiting the use of ketoconazole to cases in which no alternative therapies exist, and the European Medicines Agency has recommended the suspension of its marketing authorizations because of the potential for serious safety concerns. In this review, the Innovation and Quality in Pharmaceutical Development's Clinical Pharmacology Leadership Group (CPLG) provides a compelling rationale for the use of itraconazole as a replacement for ketoconazole in clinical DDI studies and provides recommendations on the best practices for the use of itraconazole in such studies. Various factors considered in the recommendations include the choice of itraconazole dosage form, administration in the fasted or fed state, the dose and duration of itraconazole administration, the timing of substrate and itraconazole coadministration, and measurement of itraconazole and metabolite plasma concentrations, among others. The CPLG's recommendations are based on careful review of available literature and internal industry experiences.

  15. Drug: D06732 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available r component: Loganin [CPD:C01433] Powdered product: Standards for non-pharmacopoeial crude drugs Therapeutic category of drugs... in Japan [BR:br08301] 5 Crude drugs and Chinese medicine formulations 51 Crude drugs 510 Crude drugs...ine in Japan [BR:br08304] Crude Drugs Drugs for Qi Drugs for replenishing Qi D06732 Cornus fruit; Sanshuyu Crude drugs... 5100 Crude drugs D06732 Cornus fruit (JP16) Traditional Chinese Medic

  16. Drugs and drug policy in the Netherlands

    NARCIS (Netherlands)

    Leuw, Ed.

    1991-01-01

    The Dutch parliament enacted the revised Opium Act in 1976. This penal law is part of the Dutch drug policy framework that includes tolerance for nonconforming lifestyles, risk reduction in regard to the harmful health and social consequences of drug taking, and penal measures directed against illeg

  17. The longer-term cognitive effects of adjunctive antiepileptic treatment with lacosamide in comparison with lamotrigine and topiramate in a naturalistic outpatient setting.

    Science.gov (United States)

    Helmstaedter, Christoph; Witt, Juri-Alexander

    2013-02-01

    In this retrospective controlled study, the impact of adjunctive lacosamide (LCM) on cognition in patients with epilepsy was evaluated and compared with that of topiramate (TPM) and lamotrigine (LTG) in a naturalistic outpatient setting. Cognition was investigated by means of objective assessment of executive functions (EpiTrack®) and verbal memory and by subjective ratings of self-perceived side effects (cognition, mood, and vegetative). Quality of life was assessed using the QOLIE-10 questionnaire. Patients underwent assessment at baseline and after a median follow-up interval of 32 weeks. Forty-four patients were treated with LCM, 11 with LTG, and 15 with TPM. Treatment arms differed with regard to the age at onset of epilepsy (LTG>TPM) and to seizure control from baseline to follow-up, which was best in patients whose seizures were treated with LTG (55% vs. 16% in patients whose seizures were treated with LCM and 13% in patients whose seizures were treated with TPM). Groups did not differ in the type of epilepsy, daily drug load or drug load change, nor in baseline seizure frequency. Repeated measures statistics controlling for epilepsy onset and seizure outcome showed deteriorated executive functions with TPM (F=7.5, p=0.001). On an individual level (reliable change indices), 53% of the patients whose seizures were treated with TPM showed losses in this domain (LCM 14%, LTG 27%) and none of the patients showed improvement (LCM 23%, LTG 27%; χ(2)=11.8, p=0.019). No differences in memory, quality of life, or mood were noted among patients in the three treatment arms. Subjective cognitive complaints increased in 5 of the 9 patients whose seizures were treated with TPM (LCM 1/9, LTG 0/9; χ(2)=11.9, p=0.025). The findings of this study demonstrate for the first time that the cognitive side effect profile of LCM is comparable to that of LTG and superior to that of TPM. This is indicated by both subjective and objective measures. Given the naturalistic setting and

  18. NEW DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sarkar Biresh K

    2011-05-01

    Full Text Available Incorporating an existing medicine into a new drug delivery system can significantly improve its performance in terms of efficacy, safety, and improved patient compliance. The need for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery systems. Today, drug delivery companies are engaged in the development of multiple platform technologies for controlled release, delivery of large molecules, liposome, taste-masking, oral fast- dispersing dosage forms, technology for in- soluble drugs, and delivery of drugs through intranasal, pulmonary, transdermal, vaginal, colon, and transmucosal routes.

  19. CORRELATION OF THE SERUM LEVEL OF CARBAMAZEPINE WITH SEIZURE CONTROL AND ADVERSE DRUG REACTIONS AMONG EPILEPTICS IN IBADAN, NIGERIA

    Directory of Open Access Journals (Sweden)

    Joseph O. Fadare

    2010-12-01

    Full Text Available Background: Epilepsy is a chronic neurological disorder requiring long-term treatment. Seizure control requires adequate blood levels of anti-seizure drugs. Carbarmazepine is one of the most prescribed antiepileptic drugs in Nigeria. This study was carried out to investigate the correlation between serum levels of carbamazepine and seizure control and adverse drug reactions among epileptics in Ibadan, Nigeria. Methods: In a cross-sectional study, sixty-nine patients with confirmed diagnosis of epilepsy who had been on treatment with carbamazepine alone or in combination with phenytoin for at least one month were enrolled into the study and divided into two groups based on seizure control. Drug level in pre-dose (steady state venous blood was analyzed using high performance liquid chromatography. Result: The mean serum concentration of carbamazepine (CBZ and carbamazepine-epoxide (CBZ-EP was 13.5±9.3ìg/mL and 6.34±12.61ìg/mL respectively. Patients with good seizure control had mean serum CBZ concentration of 12.7 ± 9.2ìg/mL versus 15.02 ± 9.7ìg/mL among patients with poor seizure control (P=0.33. The serum concentration of CBZ-EP in patients with good seizure control was 8.05 ± 15.2ìg/mL while it was 3.11 ± 3.5ìg/mL in the second group (P=0.122. Drowsiness was the commonest adverse drug reaction (26.1% and it did not necessitate withdrawal of the drug. Conclusion The study showed that serum level of carbamazepine does not correlate with seizure control and adverse drug reactions.

  20. IMPROVING ACCESS TO DRUGS

    Directory of Open Access Journals (Sweden)

    Max Joseph Herman

    2012-11-01

    Full Text Available Although essentially not all therapies need drug intervention, drugs is still an important components in health sector, either in preventive, curative, rehabilitative or promotion efforts. Hence the access to drugs is a main problem, either in international or national scale even to the smallest unit. The problem on access to drugs is very complicated and cannot be separated especially from pharmacy management problems; moreover in general from the overall lack of policy development and effective of health policy, and also the implementation process. With the policy development and effective health policy, rational drug uses, sufficient health service budget so a country can overcome the health problems. Besides infrastructures, regulations, distribution and cultural influences; the main obstacles for drug access is drugs affordability if the price of drugs is an important part and determined by many factors, especially the drug status whether is still patent orgenerics that significantly decrease cost of health cares and enhance the drugs affordability. The determination of essential drug prices in developing countries should based on equity principal so that poor people pay cheaper and could afford the essential drugs. WHO predicts two third of world population can not afford the essential drugs in which in developing countries, some are because of in efficient budget allocation in consequence of drug distribution management, including incorrect selection and allocation and also irrational uses. In part these could be overcome by enhancing performances on the allocation pharmacy needs, including the management of information system, inventory management, stock management and the distribution. Key words: access, drugs, essential drugs, generic drugs