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Sample records for antiepileptic drugs compelling

  1. [Endocrine effects of antiepileptic drugs].

    PubMed

    Leśkiewicz, Monika; Budziszewska, Bogusława; Lasoń, Władysław

    2008-01-01

    Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was

  2. Antiepileptic Drugs and Pregnancy Outcomes

    PubMed Central

    Wlodarczyk, Bogdan J.; Palacios, Ana M.; George, Timothy M.; Finnell, Richard H.

    2012-01-01

    The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos. PMID:22711424

  3. Antiepileptic drugs and memory.

    PubMed

    Thompson, P J

    1992-01-01

    Assessing the effects of medication on cognitive functions including memory is fraught with methodological problems. This article illustrates the range of approaches that have been employed. Medication effects have been more readily demonstrated in patients with intractable epilepsy, in whom drug dosages are higher and the risk of polytherapy is greater. Newly diagnosed cases and individuals treated with monotherapy show fewer effects. Evaluation of memory functions in most studies has been very limited, and where effects have been recorded these may well be secondary to changes in attentional level or mental processing speed.

  4. Teratogenic effects of antiepileptic drugs

    PubMed Central

    Hill, Denise S; Wlodarczyk, Bogdan J; Palacios, Ana M; Finnell, Richard H

    2010-01-01

    Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure. PMID:20518610

  5. Neurodevelopmental effects of antiepileptic drugs.

    PubMed

    Meador, Kimford J

    2002-07-01

    Although the vast majority of children born to women with epilepsy are normal, these children are at increased risk for both anatomic and cognitive impairments. Current evidence suggests that the defects are the result of in utero antiepileptic drug (AED) exposure combined with a genetic predispositon. However, the exact mechanisms underlying these effects remain to be delineated. AED polytherapy increases the risk, but it remains uncertain if specific AEDs pose an overall greater threat. Most women with epilepsy cannot avoid AEDs during pregnancy because of the greater risks posed by seizures to the mother and fetus. Therefore, current recommendations emphasize definitive diagnosis and the use of AED monotherapy at the lowest effective dose if treatment is indicated. Prenatal folate and multivitamins should also be given routinely to women of childbearing age who require AED therapy. PMID:12044257

  6. Efficacy of New Antiepileptic Drugs

    PubMed Central

    Schmidt, Dieter

    2011-01-01

    Regarding efficacy of new antiepileptic drugs (AEDs) for seizure control, there are three important clinical questions. How effective are new AEDs when corrected for the efficacy of placebo? And even more important: How do new AEDs fare in terms of seizure remission compared with established agents? And finally: Have patients seizure-free on new AEDs a better chance for lasting remission after withdrawal versus those withdrawing from older agents? The answers raise concerns. Although add-on therapy with marketed new AEDs is more effective than placebo, as expected, the treatment difference for becoming seizure-free is disappointingly small (6%; 95% CI: 4–8%; z = 6.47; p < 0.001). Although many, but not all, new AEDs have comparable efficacy to old standard drugs in well-controlled trials, none of the new AEDs is superior to old drugs in terms of seizure remission. So far, we have no antiepileptogenic treatments that prevent the development of epilepsy or modify its detrimental course. The sobering results suggest the need for novel experimental and clinical strategies for the development of more effective new AEDs that interrupt ictogenesis more effectively and prevent or abort epileptogenesis. Ideally, we need new drugs that block both ictogenesis and epileptogenesis, resulting in complete cure of epilepsy. PMID:21461260

  7. Advances in anti-epileptic drug testing.

    PubMed

    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

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

    PubMed

    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

  9. Effects of antiepileptic drugs in electrophysiological tests.

    PubMed

    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.

  10. Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies.

    PubMed

    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

  11. Epilepsy, sex hormones, and antiepileptic drugs.

    PubMed

    Mattson, R H; Cramer, J A

    1985-01-01

    Many factors associated with hormone function have an impact on the course of epilepsy. Patients with epilepsy may have disturbances in sexual function such as anovulatory cycles in women and decreased libido and potency in men. Data indicate seizures, especially those arising in the limbic system, may influence the hypothalamic pituitary axis. Antiepileptic drugs also influence sexual function through direct brain effects as well as through induced changes in pharmacokinetics of the sex steroid hormones. Pregnancy has been reported to be a time of increased seizures; however, this has often been associated with low drug levels, for reasons that include inadequate drug dose, possible changes in pharmacokinetics, and noncompliance. Some evidence suggests that hormones affect seizure frequency. Changes in seizures during the menstrual cycle (catamenial epilepsy) have been found in some women: seizures were fewer during the luteal phase but increased when progesterone levels declined. Some improvement in seizure frequency has been shown in pilot studies using medroxyprogesterone acetate, a synthetic progesterone. Current concepts of the interrelationship among epilepsy, sex hormones, and antiepileptic drugs are discussed.

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

    PubMed

    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.

    PubMed

    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. Interactions between antiepileptic drugs and hormones.

    PubMed

    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. PMID:25797888

  15. [New antiepileptic drugs: characteristics and clinical applications].

    PubMed

    Ohtsuka, Yoko

    2014-05-01

    New antiepileptic drugs (AEDs) that have been used in many other countries for more than 10 years have only recently became available for use in Japan. Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs. Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide, and perampanel are in progress. In this review, the general characteristics of the new AEDs are discussed with regards to their effectiveness, tolerability, drug interaction, safety and mechanisms of action. The effectiveness, of the new AEDs compared with established AEDs is also discussed. Clinical applications of the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam are also discussed based on our domestic experience as well as overseas reports. PMID:24912297

  16. Antiepileptic Drug Withdrawal in Dogs with Epilepsy

    PubMed Central

    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. PMID:26664952

  17. Antiepileptic Drug Withdrawal in Dogs with Epilepsy.

    PubMed

    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.

  18. Chemical properties of antiepileptic drugs (AEDs).

    PubMed

    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

  19. Reflex sympathetic dystrophy associated with antiepileptic drugs.

    PubMed

    Falasca, G F; Toly, T M; Reginato, A J; Schraeder, P L; O'Connor, C R

    1994-01-01

    Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEDs. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond to a change in AEDs, but all improved with a course of prednisone. One patient with phenobarbital (PB)-associated RSDS relapsed on inadvertent rechallenge with secobarbital. A review of the literature showed that several other fibrosing disorders are associated with AED administration, including Dupuytren's contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease. RSD associated with AEDs is important to recognize because it may result in permanent disability if treatment is delayed.

  20. The Impact of Psychoactive Drugs on Seizures and Antiepileptic Drugs.

    PubMed

    Habibi, Mitra; Hart, Felecia; Bainbridge, Jacquelyn

    2016-08-01

    Psychiatric comorbidities are very common in patients with epilepsy, and in fact, a bidirectional relationship between epilepsy and some psychiatric disorders have been identified. However, despite their high prevalence, these comorbidities are not routinely recognized or adequately treated causing a significant burden for these patients. Atypical presentations of some of these psychiatric comorbidities in epilepsy, the concern that some psychotropic drugs may lower seizure threshold worsening frequency of seizures, possibility of many drug-drug interactions, and the negative impact of some antiepileptic drugs on psychiatric conditions are some of the challenges faced by clinicians. Although the main focus in epilepsy has remained on treatment of seizures, acknowledgment of these comorbidities and their timely diagnosis and appropriate treatment not only can impact patients' quality of life but also may improve their response to antiepileptic therapies. PMID:27315249

  1. Idiosyncratic adverse reactions to antiepileptic drugs.

    PubMed

    Zaccara, Gaetano; Franciotta, Diego; Perucca, Emilio

    2007-07-01

    Idiosyncratic drug reactions may be defined as adverse effects that cannot be explained by the known mechanisms of action of the offending agent, do not occur at any dose in most patients, and develop mostly unpredictably in susceptible individuals only. These reactions are generally thought to account for up to 10% of all adverse drug reactions, but their frequency may be higher depending on the definition adopted. Idiosyncratic reactions are a major source of concern because they encompass most life-threatening effects of antiepileptic drugs (AEDs), as well as many other reactions requiring discontinuation of treatment. Based on the underlying mechanisms, idiosyncratic reactions can be differentiated into (1) immune-mediated hypersensitivity reactions, which may range from benign skin rashes to serious conditions such as drug-related rash with eosinophilia and systemic symptoms; (2) reactions involving unusual nonimmune-mediated individual susceptibility, often related to abnormal production or defective detoxification of reactive cytotoxic metabolites (as in valproate-induced liver toxicity); and (3) off-target pharmacology, whereby a drug interacts directly with a system other than that for which it is intended, an example being some types of AED-induced dyskinesias. Although no AED is free from the potential of inducing idiosyncratic reactions, the magnitude of risk and the most common manifestations vary from one drug to another, a consideration that impacts on treatment choices. Serious consequences of idiosyncratic reactions can be minimized by knowledge of risk factors, avoidance of specific AEDs in subpopulations at risk, cautious dose titration, and careful monitoring of clinical response.

  2. Antiepileptic drugs, sex hormones, and PCOS.

    PubMed

    Verrotti, Alberto; D'Egidio, Claudia; Mohn, Angelika; Coppola, Giangennaro; Parisi, Pasquale; Chiarelli, Francesco

    2011-02-01

    Reproductive endocrine dysfunction in women with epilepsy is an important issue, and in recent years there is growing evidence to support the effect on sex hormones of both epilepsy per se and various antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic-pituitary axis, thereby altering the release of sex steroid hormones. The role of laterality and severity of epilepsy is still conflicting. The use of the liver enzyme-inducing AEDs--such as phenobarbital, phenytoin, and carbamazepine--can increase serum sex hormone-binding globulin concentrations, leading to diminished bioactivity of testosterone (T) and estradiol. Valproic acid, an enzyme inhibitor, has been associated with the occurrence of reproductive endocrine disorders characterized by high serum T, free androgen index, androstenedione, dehydroepiandrosterone sulfate concentrations, and with polycystic changes in ovaries and menstrual disorders. A better understanding of the effects of AEDs on sex hormones is key to selecting the appropriate AEDs and is crucial for reproductive health in female patients.

  3. Neurodevelopmental effects of fetal antiepileptic drug exposure.

    PubMed

    Velez-Ruiz, Naymee J; Meador, Kimford J

    2015-03-01

    Many studies investigating cognitive outcomes in children of women with epilepsy report an increased risk of mental impairment. Verbal scores on neuropsychometric measures may be selectively more involved. While a variety of factors contribute to the cognitive problems of children of women with epilepsy, antiepileptic drugs (AEDs) appear to play a major role. The mechanisms by which AEDs affect neurodevelopmental outcomes remain poorly defined. Animal models suggest that AED-induced apoptosis, altered neurotransmitter environment, and impaired synaptogenesis are some of the mechanisms responsible for cognitive and behavioral teratogenesis. AEDs that are known to induce apoptosis, such as valproate, appear to affect children's neurodevelopment in a more severe fashion. Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains, and these appear to persist at least until the age of 6. Some studies have shown neurodevelopmental deficiencies associated with the use of phenobarbital and possibly phenytoin. So far, most of the investigations available suggest that fetal exposures to lamotrigine or levetiracetam are safer with regard to cognition when compared with other AEDs. Studies on carbamazepine show contradictory results, but most information available suggests that major poor cognitive outcomes should not be attributed to this medication. Overall, children exposed to polytherapy prenatally appear to have worse cognitive and behavioral outcomes compared with children exposed to monotherapy, and with the unexposed. There is an increase risk of neurodevelopmental deficits when polytherapy involves the use of valproate versus other agents. PMID:25693658

  4. Antiepileptic drug treatment strategies in neonatal epilepsy.

    PubMed

    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

  5. Availability of antiepileptic drugs across Europe.

    PubMed

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

    2015-12-01

    Europe consists of 53 countries with widely different economic conditions and different political, educational, and health care systems. This study was aimed at determining the availability of antiepileptic drugs (AEDs) across Europe. An electronic questionnaire was submitted to all 43 European chapters of the International League Against Epilepsy (ILAE). Outcome measures were availability of older, newer, and newest AEDs, generic products, indications, reimbursement rules, and reasons for lack of availability of AEDs. Countries were divided according to economic status as defined by the World Bank. Thirty-four chapters (79%) provided data. There were large differences in AED availability across countries, especially between high-income countries and the other countries. The newest AEDs were not available in any of the 12 non-high-income countries. Availability was higher in countries with public reimbursement systems. Reimbursement policies ranged from full reimbursement for all AEDs to complete lack of reimbursement. Main hurdles for poor access to AEDs included lack of regulatory approval, high prices and reimbursement restrictions. The availability of AEDs differs across European countries, with many hurdles hampering access to epilepsy medicines, particularly to new medications. These findings raise major concerns on the quality of epilepsy care in many countries. PMID:26477534

  6. Molecular Targets for Antiepileptic Drug Development

    PubMed Central

    Meldrum, Brian S.; Rogawski, Michael A.

    2007-01-01

    Summary This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the α subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, α2–δ voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABAA receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABAB and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABAA receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the

  7. Use of antiepileptic drugs in hepatic and renal disease.

    PubMed

    Asconapé, Jorge J

    2014-01-01

    The use of antiepileptic drugs in patients with renal or hepatic disease is common in clinical practice. Since the liver and kidney are the main organs involved in the elimination of most drugs, their dysfunction can have important effects on the disposition of antiepileptic drugs. Renal or hepatic disease can prolong the elimination of the parent drug or an active metabolite leading to accumulation and clinical toxicity. It can also affect the protein binding, distribution, and metabolism of a drug. The protein binding of anionic acidic drugs, such as phenytoin and valproate, can be reduced significantly by renal failure, causing difficulties in the interpretation of total serum concentrations commonly used in clinical practice. Dialysis can further modify the pharmacokinetic parameters or result in significant removal of the antiepileptic drugs. Antiepileptic drugs that are eliminated unchanged by the kidneys or undergo minimal metabolism include gabapentin, pregabalin, vigabatrin, and topiramate when used as monotherapy. Drugs eliminated predominantly by biotransformation include phenytoin, valproate, carbamazepine, tiagabine, and rufinamide. Drugs eliminated by a combination of renal excretion and biotransformation include levetiracetam, lacosamide, zonisamide, primidone, phenobarbital, ezogabine/retigabine, oxcarbazepine, eslicarbazepine, ethosuximide, and felbamate. Drugs in the latter group can be used cautiously in patients with either renal or liver failure. Antiepileptic drugs that are at high risk of being extracted by hemodialysis include ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin and topiramate. The use of antiepileptic drugs in the presence of hepatic or renal disease is complex and requires great familiarity with the pharmacokinetics of these agents. Closer follow-up of the patients and more frequent monitoring of serum concentrations are required to optimize clinical outcomes. PMID:24365310

  8. Hypoactive sexual desire disorder caused by antiepileptic drugs

    PubMed Central

    Singh, M.; Bathla, Manish; Martin, A.; 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. PMID:26157303

  9. Current approaches to the use of generic antiepileptic drugs.

    PubMed

    Krämer, G; Biraben, A; Carreno, M; Guekht, A; de Haan, G J; Jedrzejczak, J; Josephs, D; van Rijckevorsel, K; Zaccara, G

    2007-08-01

    Generic substitution is encouraged as a cost containment strategy for the management of health care resources. However, in epilepsy, the consequences of loss of symptom control are important, and antiepileptic drugs have narrow therapeutic indices. For this reason, generic substitution may be problematic, and certain health authorities have excluded antiepileptic drugs from overall policy recommendations on generic prescribing. The absence of bioequivalence data among generic forms and the relatively broad criteria for bioequivalence with the branded drug allow differences in drug exposure to arise that may be clinically relevant and necessitate monitoring of plasma levels when switching formulations to avoid loss of seizure control or emergence of side effects. Management of these issues carries a significant cost, which should be weighed carefully against the cost savings acquired when purchasing the drug. Both physicians and patients have a right to be informed and approve before pharmacists make a generic substitution or switch between generics.

  10. Cutaneous Adverse Drug Reactions in Dogs Treated with Antiepileptic Drugs

    PubMed Central

    Koch, Tina; Mueller, Ralf S.; Dobenecker, Britta; Fischer, Andrea

    2016-01-01

    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 AED 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 AED 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 were further investigated as potential diagnostic methods to confirm AED hypersensitivity. They were of high specificity but sensitivity and positive predictive value appeared inappropriate to recommend their routine use in clinical practice. PMID:27148543

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

    PubMed Central

    HANAYA, Ryosuke; ARITA, Kazunori

    2016-01-01

    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

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

    PubMed

    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.

  13. The rise and fall of borax as an antiepileptic drug.

    PubMed

    Jensen, John P A

    2006-04-01

    Five hundred eighty-six patients with epilepsy were treated with borax (hydrated sodium tetraborate) between 1912 and 1948 at the Kolonien Filadelfia Epilepsy Hospital, Dianalund, Denmark. A rough estimation shows that less than 5% experienced a more than 50% reduction in the total number of seizures. Charts were reviewed to find a connection between the concept of Bacillus epilepticus (1916) and the so-called renaissance of borax treatment described in 1923, and to find an explanation for the popularity of this seemingly ineffective antiepileptic drug.

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

    PubMed

    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.

  15. Old versus New: Why Do We Need New Antiepileptic Drugs?

    PubMed Central

    Lee, Sang Kun

    2014-01-01

    Achieving complete seizure remission without adverse events is the goal of epilepsy treatment. Recently, many new antiepileptic drugs (AEDs) have been developed. Even though the efficacy of new AEDs is not stronger than that of old AEDs, there are advantages in using new AEDs. They have unique or different mechanisms of action that enable the creation of possible synergistic combinations. They usually exhibit fewer or no pharmacokinetic drug interactions. Furthermore, the response to AEDs varies individually. A similar efficacy does not imply a similar response from all patients. Many new AEDs have fewer adverse events, including induction of congenital malformations. Other concerns about the long-term effects of established AEDs, such as bone health and development of atherosclerosis, may be alleviated by the use of new AEDs. New AEDs are needed to achieve better care of patients with epilepsy. PMID:25625087

  16. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    PubMed Central

    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

  17. Neurological teratogenic effects of antiepileptic drugs during pregnancy

    PubMed Central

    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.

  18. Modifications of Antiepileptic Drugs for Improved Tolerability and Efficacy

    PubMed Central

    Landmark, Cecilie Johannessen; Johannessen, Svein I.

    2008-01-01

    Introduction A large number of antiepileptic drugs (AEDs) are available today, but they may not be satisfactory regarding clinical efficacy, tolerance, toxicity or pharmacokinetic properties. The purpose of this review is to focus upon the rationale behind the chemical modifications of several recently marketed AEDs or drugs in development and to categorize them according to the main purposes for the improvements: better efficacy or tolerability accompanied by improved pharmacokinetic properties. Material and Method AEDs that have been chemically modified to new derivatives during the last years are reviewed based on recent publications and PubMed-searches. Results and Discussion Improvement in pharmacokinetic parameters may affect both tolerability and efficacy. Modifications to improve tolerability include various valproate analogues, divided into aliphatic amides, cyclic derivatives or amino acid conjugates. Furthermore, there are the carbamazepine analogues oxcarbazepine and eslicarbazepine, the felbamate analogues fluorofelbamate and carisbamate (RWJ 33369), and the lamotrigine analogue JZP-4. The levetiracetam analogues brivaracetam and seletracetam and the derivatives of gabapentin, pregabalin and XP13512, have improved selectivity compared to their parent compounds. Other new drugs have new mechanisms of action related to GABA and glutamate receptors; the glutamate antagonists like topiramate (talampanel and NS-1209), and GABAA receptor agonists, benzodiazepine or progesterone analogues (ELB-139 and ganaxolone). Conclusion Further challenges for development of new AEDs include investigations of target molecules affected by pathophysiological processes and detailed structure-activity relationships with focus on stereoselectivity. These potential drugs may become of importance in future drug therapy in epilepsy and other CNS disorders. PMID:19787095

  19. Effects of the antiepileptic drug carbamazepine on human erythrocytes.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Villena, Fernando; Sotomayor, Carlos P

    2006-12-01

    The structural effects of the antiepileptic drug carbamazepine (CBZ) on the human erythrocyte membrane and molecular models have been investigated in the present work. This report presents the following evidence that CBZ interacts with red cell membranes: (a) X-ray diffraction and fluorescence spectroscopy of phospholipid bilayers showed that CBZ perturbed a class of lipids found in the outer moiety of the erythrocyte membrane; (b) in isolated unsealed human erythrocytes (IUM) the drug induced a disordering effect on the polar head groups and acyl chains of the membrane lipid bilayer; (c) in scanning electron microscopy (SEM) studies on human erythrocytes the formation of echinocytes was observed, due to the preferential insertion of CBZ in the outer monolayer of the red cell membrane. The effects of the drug detected in the present work were observed at concentrations of the order of those currently appearing in serum when it is therapeutically administered. This is the first time that toxic effects of carbamazepine on the human erythrocyte membrane have been described. PMID:16844339

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

    ERIC Educational Resources Information Center

    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…

  1. The antiepileptic drug carbamazepine affects sodium transport in toad epithelium.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Cardenas, Hernán

    2006-09-01

    The present work investigates the effects of the antiepileptic drug carbamazepine (CBZ) on sodium transport in the isolated skin of the toad Pleurodema thaul. A submaximal concentration of the drug (0.2 mM) applied to the outer surface of the epithelium increased the electrical parameters short-circuit current (Isc) and potential difference (PD) by over 28%, whereas only a higher concentration (1 mM) induced over a 45% decrease in these parameters when applied to the inner surface. The amiloride test showed that the outer surface stimulatory effect was accompanied by an increase and the inner surface inhibitory effect by a decrease in the sodium electromotive force (ENa). Exploration of these effects of CBZ on the outer surface showed that 0.2 mM increased net Na+ (22Na) influx by 20% and 0.6 mM CBZ decreased Na+ mucosa-serosa flux by 19%, a result in agreement with the finding that higher concentrations of CBZ applied to the inner surface not only decreased ENa but also sodium conductance (GNa). PMID:16542818

  2. Polycystic ovary syndrome in patients on antiepileptic drugs

    PubMed Central

    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

  3. Cognitive side-effects of antiepileptic drugs in children.

    PubMed

    Ijff, Dominique M; Aldenkamp, Albert P

    2013-01-01

    Although the causes of cognitive impairment in patients with epilepsy have not been completely elucidated, three factors are clearly involved: the underlying etiology of epilepsy, the effects of seizures or the epileptiform EEG discharges themselves, and the central nervous system effects of antiepileptic drugs (AEDs). All commonly used AEDs have some effect on cognitive function, and the effect may be substantial when crucial functions are involved, such as learning in children. With phenobarbital, there is a high risk for serious cognitive effects impacting attention and memory. Phenytoin may affect mental speed, mainly in higher dosing and polytherapy. Moderate monotherapy doses do not seem to induce much effect. Valproate does not seem to impair cognition if sufficiently controlled for hyperammonemia. For carbamazepine, there are conflicting reports, which may be due to selection bias or dosing. For oxcarbazepine, there is no evidence for any detrimental change compared to valproate but mild improvements on attentional tests. For topiramate, there is clear evidence for topiramate-induced cognitive impairment (attention, memory, and language function) in adults and children. Although data is sketchy, levetiracetam does not seem to have a negative impact on cognition. For lamotrigine, there is evidence of a cognitive-enhancing effect on attention. No evidence for cognitive side-effects has been found for vigabatrin. Ethosuximide is not associated with cognitive impairment although the evidence is sketchy. For gabapentin, tiagabine, zonisamide, and rufinamide no studies in children are available. PMID:23622218

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

    PubMed Central

    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

  5. Epilepsy, sex hormones and antiepileptic drugs in female patients.

    PubMed

    Verrotti, Alberto; D'Egidio, Claudia; Coppola, Giangennaro; Parisi, Pasquale; Chiarelli, Francesco

    2009-12-01

    Women with epilepsy have a higher incidence of reproductive endocrine disorders than the general female population. These alterations include polycystic ovary syndrome, hyperandrogenemia, infertility, hypothalamic amenorrhea and hyperprolactinemia. Reproductive dysfunction is attributed both to epilepsy itself and to antiepileptic drugs (AEDs). Focal epileptic discharges from the temporal lobe may have a direct influence on the function of the hypothalamic-pituitary axis, thus altering the release of sex steroid hormones, including the production of luteinizing hormone, follicle-stimulating hormone, gonadotropin-releasing hormone and prolactin. AEDs may modulate hormone release from the hypothalamic-pituitary-gonadal axis and they may alter the metabolism of sex hormones and their binding proteins. Hepatic enzyme-inducing AEDs, such as carbamazepine and phenytoin, may be most clearly linked to altered metabolism of sex steroid hormones, but valproic acid, an enzyme inhibitor, has also been associated with a frequent occurrence of polycystic ovary syndrome and hyperandrogenism in women with epilepsy. Therefore, treatment of epilepsy and selection of AEDs are important for reproductive health in female patients. The aim of the present review is to critically evaluate the recently published data concerning the interactions between sex hormones, epilepsy and AEDs.

  6. The antiepileptic drug phenytoin affects sodium transport in toad epithelium.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Cárdenas, Hernan

    2006-01-01

    The effects of phenytoin on isolated Pleurodema thaul toad skin were investigated. Low (micromolar) concentrations of the antiepileptic agent applied to the outside surface of the toad epithelium increased the electrical parameters (short-circuit current and potential difference) by over 40%, reflecting stimulation of Na(+) transport, whereas higher (millimolar concentrations, outside and inside surface) decreased both electric parameters, the effect being greater at the inside surface (40% and 80% decrease, respectively). The amiloride test showed that the stimulatory effect was accompanied by an increase and the inhibitory effect by a decrease in the sodium electromotive force (ENa). It is concluded that the drug interaction with membrane lipid bilayers might result in a distortion of the lipid-protein interface contributing to disturbance of Na(+) epithelial channel activity. After applying the Na(+)-K(+)-ATPase blocker ouabain and replacing the Na(+) ions in the outer Ringer's solution by choline, it was concluded that both active and passive transport are involved in sodium absorption, although active transport predominates. PMID:16314149

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

    PubMed

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

    2016-07-01

    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

  8. Initial treatment of epilepsy with antiepileptic drugs: pediatric issues.

    PubMed

    Sankar, Raman

    2004-11-23

    The selection of an antiepileptic drug (AED) for initial treatment of epilepsy in infancy, childhood, and adolescence should ideally be made after a clear syndromic diagnosis of the patient's seizure disorder. A common cause of failure of the first AED is erroneous diagnosis. The availability of new-generation AEDs has expanded the choice of available agents with comparable efficacy for most syndromes. Efficacy data based on class I or II evidence are not available for many syndromes of childhood, and selection must therefore be based on the best data available. It is also important to assess the relative toxicity and tolerability of AEDs in making the selection. It is especially important to appreciate age-specific organ toxicities. Moreover, the use of AEDs in childhood requires an understanding of their neurobehavioral effects. Important neuropsychiatric co-morbidities in children with epilepsy include attention deficit/hyperactivity disorder, autistic spectrum disorders, depression and anxiety, and thought disorders. These problems can be exacerbated or ameliorated by specific AEDs. The effect of AEDs on body weight, insulin sensitivity, lipid profile, and bone health is becoming better appreciated. Newer AEDs may offer significant advantages in this regard. Co-morbid migraine in children with epilepsy may benefit from some AEDs. There remains a continuing need for the development of newer AEDs that are targeted for the developing brain to improve the efficacy and tolerability of treatment in childhood seizure disorders. PMID:15557549

  9. Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs

    PubMed Central

    Jia, Kailiang; Grill, Brock; Dawson-Scully, Ken

    2016-01-01

    The microscopic nematode Caenorhabditis elegans has emerged as a valuable model for understanding the molecular and cellular basis of neurological disorders. The worm offers important physiological similarities to mammalian models such as conserved neuron morphology, ion channels, and neurotransmitters. While a wide-array of behavioral assays are available in C. elegans, an assay for electroshock/electroconvulsion remains absent. Here, we have developed a quantitative behavioral method to assess the locomotor response following electric shock in C. elegans. Electric shock impairs normal locomotion, and induces paralysis and muscle twitching; after a brief recovery period, shocked animals resume normal locomotion. We tested electric shock responses in loss-of-function mutants for unc-25, which encodes the GABA biosynthetic enzyme GAD, and unc-49, which encodes the GABAA receptor. unc-25 and unc-49 mutants have decreased inhibitory GABAergic transmission to muscles, and take significantly more time to recover normal locomotion following electric shock compared to wild-type. Importantly, increased sensitivity of unc-25 and unc-49 mutants to electric shock is rescued by treatment with antiepileptic drugs, such as retigabine. Additionally, we show that pentylenetetrazol (PTZ), a GABAA receptor antagonist and proconvulsant in mammalian and C. elegans seizure models, increases susceptibility of worms to electric shock. PMID:27668426

  10. Breastfeeding in Children of Women Taking Antiepileptic Drugs

    PubMed Central

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

    2014-01-01

    IMPORTANCE Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P italic> .001 [adjusted IQ worse by 7–13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, −0.1; 95% CI, −0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95% CI, 2–10] points higher for folate, P = .005), and breastfeeding

  11. Antiepileptic drugs in the treatment of psychiatric disorders.

    PubMed

    Kaufman, Kenneth R

    2011-05-01

    The clinical interface between psychiatry and neurology is epilepsy; the pharmacological expression of this interface is antiepileptic drugs (AEDs), as they are used to treat both epilepsy and psychiatric disorders, especially bipolar disorders. The prevalence of psychiatric comorbidity and the risk of suicidal behavior/ideation/suicide are markedly increased in patients with epilepsy (PWE). Though AEDs receive initial indications for the treatment of epilepsy, currently the majority of AEDs are used to treat pain and psychiatric disorders. Thus in selecting the appropriate AEDs for treatment of PWE, consideration should be given to which AEDs best treat the epileptic disorder and the psychiatric comorbidity. This review is an overview of 21 AEDs in which negative psychotropic properties, approved indications in psychiatry, off-label studied uses in psychiatry, and principal uses in psychiatry are presented with literature review. A total of 40 psychiatric uses have been identified. Of the 21 AEDs reviewed, only 5 have U.S. Food and Drug Administration and/or European Medicines Agency psychiatric approval for limited uses; the majority of AEDs are used off-label. Many of these off-label uses are based on case reports, open-label studies, and poorly controlled or small-sample-size studies. In some instances, off-label use persists in the face of negative pivotal trials. Further placebo-controlled (augmentation and monotherapy) parallel-arm research with active comparators is required in the complex field of AED treatment of psychiatric disorders to minimize the treatment gap not only for PWE with psychiatric disorders, but also for psychiatric patients who would benefit from properly studied AEDs while minimizing adverse effects.

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

    PubMed

    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. Role of antiepileptic drugs in the management of eating disorders.

    PubMed

    McElroy, Susan L; Guerdjikova, Anna I; Martens, Brian; Keck, Paul E; Pope, Harrison G; Hudson, James I

    2009-01-01

    Growing evidence suggests that antiepileptic drugs (AEDs) may be useful in managing some eating disorders. In the present paper, we provide a brief overview of eating disorders, the rationale for using AEDs in the treatment of these disorders and review the data supporting the effectiveness of specific AEDs in the treatment of patients with eating disorders. In addition, the potential mechanisms of action of AEDs in these conditions are discussed. Of the available AEDs, topiramate appears to have the broadest spectrum of action as an anti-binge eating, anti-purging and weight loss agent, as demonstrated in two placebo-controlled studies in bulimia nervosa and three placebo-controlled studies in binge-eating disorder (BED) with obesity. Topiramate may also have beneficial effects in night-eating syndrome and sleep-related eating disorder, but controlled trials in these conditions are needed. The results of one small controlled study suggest that zonisamide may have efficacy in BED with obesity. However, both topiramate and zonisamide are associated with adverse effect profiles that may limit their use in patients with eating disorders. Phenytoin may be effective in some patients with compulsive binge eating, particularly if co-morbid EEG abnormalities are present, but available data are too varied to allow definitive conclusions to be made. Carbamazepine and valproate may be effective in treating patients with bulimia nervosa or anorexia nervosa when they are used to treat an associated psychiatric (e.g. mood) or neurological (e.g. seizure) disorder; otherwise, both agents, particularly valproate, are associated with weight gain. In conclusion, AEDs have an emerging role in the management of some eating disorders.

  14. The long-term safety of antiepileptic drugs.

    PubMed

    Gaitatzis, Athanasios; Sander, Josemir W

    2013-06-01

    Antiepileptic drugs (AEDs) are used by millions of people worldwide for the treatment of epilepsy, as well as in many other neurological and psychiatric conditions. They are frequently associated with adverse effects (AEs), which have an impact on the tolerability and success of treatment. Half the people who develop intolerable AEs discontinue treatment early on after initiation, while the majority of people will continue to be exposed to their effects for long periods of time. The long-term safety of AEDs reflects their potential for chronic, cumulative dose effects; rare, but potentially serious late idiosyncratic effects; late, dose-related effects; and delayed, teratogenic or neurodevelopmental effects. These AEs can affect every body system and are usually insidious. With the exception of delayed effects, most other late or chronic AEs are reversible. To date, there is no clear evidence of a carcinogenic effect of AEDs in humans. While physicians are aware of the long-term AEs of old AEDs (the traditional liver enzyme-inducing AEDs and valproate), information about AEs of new AEDs (such as lamotrigine, levetiracetam, oxcarbazepine, topiramate or zonisamide), particularly of their teratogenic effects, has emerged over the years. Sporadic publications have raised issues about AEs of the newer AEDs eslicarbazepine, retigabine, rufinamide, lacosamide and perampanel but their long-term safety profiles may take years to be fully appreciated. Physicians should not only be aware of the late and chronic AEs of AEDs but should systematically enquire and screen for these according to the individual AED AE profile. Care should be taken for individuals with comorbid conditions that may render them more susceptible to specific AEs. Prevention and appropriate management of long-term AED AEs is expected to improve adherence to treatment, quality of life and control of epilepsy. PMID:23673774

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed Central

    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

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

    PubMed

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

    2016-05-01

    To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, magnesium sulfate, oxcarbazepine, phenytoin, primidone, tiagabine, topiramate, valproic acid, and vigabatrin. Dexamethasone and temozolomide were used as a negative and positive control respectively. Our results showed temozolomide and oxcarbazepine significantly inhibited glioblastoma cell growth and reached IC50 at therapeutic concentrations. The other antiepileptic drugs screened were unable to reach IC50 at therapeutic concentrations. The metabolites of oxcarbazepine were also unable to reach IC50. Dexamethasone, ethosuximide, levetiracetam, and vigabatrin showed some growth enhancement though they did not reach statistical significance. The growth enhancement effects of ethosuximide, levetiracetam, and vigabatrin found in the study may indicate that these compounds should not be used for prophylaxis or short term treatment of epilepsy in glioblastoma. While valproic acid and oxcarbazepine were effective, the required dose of valproic acid was far above that used for the treatment of epilepsy and the metabolites of oxcarbazepine failed to reach significant growth inhibition ruling out the use of oral oxcarbazepine or valproic acid as monotherapy in glioblastoma. The possibility of using these compounds as local treatment is a future area of study. PMID:26758059

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

    SciTech Connect

    Myllynen, Paeivi . E-mail: paivi.k.myllynen@oulu.fi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

    2005-09-01

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

  20. Psychotropic and Antiepileptic Drug Treatment in Early Childhood Special Education. Final Report.

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.

    The effectiveness of psychotropic and antiepileptic drug treatment was investigated with approximately 2500 children receiving educational services in early childhood special education programs. The study consisted of three phases: phase 1 in which all teachers were surveyed to determine the prevalence of drug therapy and patterns of usage, phase…

  1. Adjusting to a seizure-free "new normal" life following discontinuation of antiepileptic drugs during adolescence.

    PubMed

    Chiu, Ya-Ping; Lee, Tzu-Ying; Lin, Kuang-Lin; Laadt, Virginia L

    2014-04-01

    This qualitative study sought to understand how children in adolescence adjust to their newly acquired normal life without epilepsy, following discontinuation of antiepileptic drugs during this dynamic period of growth and development. Three major themes with subthemes were identified: 1) setting the body and mind free; 2) engaging in self-regulation; and 3) protection by significant others. A sense of relief from constraints related to treatment schedules, special diets, and avoiding seizure-provoking activities was expressed by all participants. Freedom from side effects of the antiepileptic drugs improved life at home and school. Most of the participants said that they were not worried about seizure recurrence but would use caution against a possible relapse. Family members also must adjust to a new lifestyle. Medical staff needs to provide support and adequate care to adolescents during their period of identity adjustment following antiepileptic drug discontinuation. PMID:24632354

  2. Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.

    PubMed

    Van Ameringen, Michael; Mancini, Catherine; Pipe, Beth; Bennett, Mark

    2004-01-01

    Pharmacotherapy for anxiety disorders is an active area of research. A variety of drug groups have been shown to be effective in treating many of the anxiety disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered first-line agents for virtually all anxiety disorders. There is a clinical need for alternative drug treatments, as many patients do not achieve a complete response and experience significant adverse effects. The successful use of antiepileptic drugs in mood disorders has led clinicians and researchers to investigate their potential efficacy in other psychiatric disorders, particularly in anxiety disorders. There have been a number of investigations conducted in the form of case reports, case series and open-label trials, suggesting the potential usefulness of antiepileptic drug treatment in a variety of anxiety disorders. More reliable evidence for the use of antiepileptic drugs in anxiety disorders can be gleaned from recent placebo-controlled trials. Thus far, the strongest placebo-controlled evidence has demonstrated the efficacy of pregabalin in treating social phobia and generalised anxiety disorder, while smaller or less robust controlled trials have suggested the potential efficacy of gabapentin in social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid in panic disorder. Antiepileptic drugs may have a place in the treatment of anxiety disorders; however, further investigation is warranted to determine in what circumstances they should be used as monotherapy or as augmenting agents in individuals who are partially or non-responsive to conventional therapy.

  3. Changes in Antiepileptic Drug Prescribing Patterns in Large Institutions: Preliminary Results of a Five-Year Experience.

    ERIC Educational Resources Information Center

    Poindexter, Ann R.; And Others

    1993-01-01

    Antiepileptic drug prescriptions were analyzed for 337 institutionalized individuals with mental retardation, over 54 months. Results indicated decreasing numbers of individuals receiving (1) more than 2 antiepileptic drugs concurrently, and (2) barbiturates. Over 90% of a group undergoing barbiturate taper maintained the same or improved seizure…

  4. Antiepileptic drugs for the treatment of neuropathic pain: A systematic review

    PubMed Central

    Vargas-Espinosa, Maríam L.; Sanmartí-García, Gemma; Vázquez-Delgado, Eduardo

    2012-01-01

    Many therapies have been proposed for the management of neuropathic pain, and they include the use of different antiepileptic drugs. However, the lack of high quality studies indicates that results on the different neuropathic disorders under study do not recommend a particular drug treatment. This study makes a systematic review of the published literature on the use of several antiepileptic drugs to treat neuropathic pain, and has the objective of considering both its clinical characteristics and pharmacological use, which will depend on their level of scientific evidence and will follow the principles of evidence-based dentistry. The articles were stratified according to their scientific evidence using the SORT criteria (Strength of Recommendation Taxonomy), and it included those articles that only have level 1 or 2. Randomized clinical trials were stratified according to their level of quality using the JADAD scale, an instrument described by Jadad et al. (7). to assess the quality of clinical trials, while studies with a level below 3 were discarded. Recently, type A or B recommendations are given in favor or against the use of antiepileptic drugs to treat neuropathic pain on the basis of their scientific quality. Key words:Neuropathic pain, antiepileptic drugs (AEDs), trigeminal neuralgia, glossopharyngeal neuralgia, post- herpetic neuralgia, burning mouth syndrome, persistent idiopathic facial pain. PMID:22549682

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

    PubMed Central

    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

  6. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth

    PubMed Central

    Dean, J; Hailey, H; Moore, S; Lloyd, D; Turnpenny, P; Little, J

    2002-01-01

    Objective: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. Design: Retrospective population based study. Setting: Population of the Grampian region of Scotland. Participants: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. Main outcome measures: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. Results: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). Conclusion: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation. PMID:11950853

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed Central

    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 the various hypotheses of drug resistance and to explore possible links to the severity of epilepsy. The observation that a high frequency of seizures prior to onset of treatment is a prognostic signal of increased severity and future drug failure suggests that common neurobiological factors may underlie both disease severity and pharmacoresistance. Such a link has been proposed for depression; however, the evidence for a direct mechanistic link, genetic or otherwise, between drug response and disease severity of human epilepsy is still elusive. Although emerging data from experimental studies suggest that alterations in GABAA receptors may present one example of a mechanistic link, clearly more work is needed to explore whether common neurobiological factors may underlie both epilepsy severity and drug failure. PMID:19421380

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

    PubMed

    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. A prospective study of adverse drug reactions to antiepileptic drugs in children

    PubMed Central

    Anderson, Mark; Egunsola, Oluwaseun; Cherrill, Janine; Millward, Claire; Fakis, Apostolos; Choonara, Imti

    2015-01-01

    Objectives To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. Setting A single centre prospective observational study. Participants Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. Primary and secondary outcomes Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. Results 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. Conclusions Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children. Trail registration number EudraCT (2007-000565-37). PMID:26033949

  14. Adverse reactions to antiepileptic drugs: a follow-up study of 355 patients with chronic antiepileptic drug treatment. Collaborative Group for Epidemiology of Epilepsy.

    PubMed

    1988-01-01

    Three hundred fifty-five patients receiving chronic antiepileptic drug (AED) treatment were followed in 15 university and hospital centers for an average of 11 months to assess the effects of intensive monitoring of adverse drug reactions (ADRs) on the frequency of reports and on the overall management of epilepsy. One hundred forty-eight patients (41.6%) had one or more ADRs during the entire follow-up period. ADRs were reported by 31% of patients at admission and by 20% at last visit, with a downward trend in the number of reports. Concurrently, the number of patients who were seizure-free rose from 24.5 to 42.8%. During the observation period, the number of prescriptions fell from 640 to 568, mostly for phenobarbital (PB), phenytoin (PHT), and valproate (VPA). The outcome of the most common ADR was only partially related to drug changes. Even with the limitations of the unstandardized criteria used for ADR reporting, the present study shows that intensive monitoring of drug-related clinical events is not only a valuable tool to provide a comprehensive survey of drug toxicity in clinical practice, but is also an educational effort to improve the quality of care for patients with epilepsy. PMID:3191896

  15. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics.

    PubMed

    Spina, Edoardo; Pisani, Francesco; de Leon, Jose

    2016-04-01

    Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses≥1200mg/day), topiramate doses≥400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID:26896788

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

    PubMed

    Haneef, Zulfi; Levin, Harvey S; Chiang, Sharon

    2015-06-01

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

  17. Prenatal Exposure to Antiepileptic Drugs and Dental Agenesis

    PubMed Central

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

    2014-01-01

    Objective The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used. Methods Data on 214 exposed and 255 unexposed children, aged 12–18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis. Results Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8–3.6]). The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3–7.4]) in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4–51.9]) in children exposed to valproate and carbamazepine or oxcarbazepine in combination. Conclusions The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate. PMID:24416231

  18. Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII).

    PubMed

    Bialer, Meir; Johannessen, Svein I; Kupferberg, Harvey J; Levy, René H; Perucca, Emilio; Tomson, Torbjörn

    2004-01-01

    The Seventh Eilat Conference on New Antiepileptic Drugs (AEDs) (EILAT VII) took place in Villasimius, Sardinia, Italy from the 9th to 13th May 2004. Basic scientists, clinical pharmacologists and neurologists from 24 countries attended the conference,whose main themes included advances in pathophysiology of drug resistance, new AEDs in pediatric epilepsy syndromes, modes of AED action and spectrum of adverse effects and a re-appraisal of comparative responses to AED combinations. Consistent with previous formats of this conference, the central part of the conference was devoted to a review of AEDs in development, as well as updates on second-generation AEDs. This article summarizes the information presented on drugs in development, including atipamezole, BIA-2-093, fluorofelbamate, NPS 1776, pregabalin, retigabine, safinamide, SPM 927, stiripentol, talampanel,ucb 34714 and valrocemide (TV 1901). Updates on felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine,topiramate, vigabatrin, zonisamide, new oral and parenteral formulations of valproic acid and SPM 927 and the antiepileptic vagal stimulator device are also presented.

  19. Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years

    PubMed Central

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

    2014-01-01

    The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6 years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales. Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System—Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD. The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine

  20. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age.

    PubMed

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

    2011-02-01

    We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and

  1. Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age

    PubMed Central

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

    2011-01-01

    We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and

  2. The effects of antiepileptic drugs on cognitive functional magnetic resonance imaging

    PubMed Central

    Beltramini, Guilherme Coco; Cendes, Fernando

    2015-01-01

    The cognitive dysfunction caused by antiepileptic drugs (AEDs) has been extensively described, although the mechanisms underlying such collateral effects are still poorly understood. The combination of functional magnetic resonance imaging (fMRI) studies with pharmacological intervention (pharmaco-MRI or ph-MRI) offers the opportunity to investigate the effect of drugs such as AEDs on brain activity, including cognitive tasks. Here we review the studies that investigated the effects of AEDs [topiramate (TPM), lamotrigine (LMT), carbamazepine (CBZ), pregabalin (PGB), valproate (VPA) and levetiracetam (LEV)] on cognitive fMRI tasks. Despite the scarcity of fMRI studies focusing on the impact of AEDs on cognitive task, the results of recent work have provided important information about specific drug-related changes of brain function. PMID:25853082

  3. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI).

    PubMed

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

    2013-01-01

    The Eleventh Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT XI, took place in Eilat, Israel from the 6th to 10th of May 2012. About 100 basic scientists, clinical pharmacologists and neurologists from 20 countries attended the conference, whose main themes included "Indications overlapping with epilepsy" and "Securing the successful development of an investigational antiepileptic drug in the current environment". 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 EILAT X report, the current manuscript focuses only on the preclinical and clinical pharmacology of AEDs that are currently in development. These include brivaracetam, 2-deoxy-glucose, ganaxolone, ICA-105665, imepitoin, NAX 801-2, perampanel and other AMPA receptor antagonists, tonabersat, valnoctamide and its homologue sec-propylbutylacetamide (SPD), VX-765 and YK3089. Since the previous Eilat conference, retigabine (ezogabine) has been marketed and four newer AEDs in development (NAX 810-2, SPD, tonabersat and VX-765) are included in this manuscript.

  4. Epileptiform activity and cognitive deficits in SNAP-25(+/-) mice are normalized by antiepileptic drugs.

    PubMed

    Corradini, Irene; Donzelli, Andrea; Antonucci, Flavia; Welzl, Hans; Loos, Maarten; Martucci, Roberta; De Astis, Silvia; Pattini, Linda; Inverardi, Francesca; Wolfer, David; Caleo, Matteo; Bozzi, Yuri; Verderio, Claudia; Frassoni, Carolina; Braida, Daniela; Clerici, Mario; Lipp, Hans-Peter; Sala, Mariaelvina; Matteoli, Michela

    2014-02-01

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble NSF attachment protein receptor complex and modulates voltage-gated calcium channels activity. The Snap25 gene has been associated with schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. We used SNAP-25 heterozygous (SNAP-25(+/-)) mice to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior. As interactions of genotype with the specific laboratory conditions may impact behavioral results, the study was performed through a multilaboratory study in which behavioral tests were replicated in at least 2 of 3 distinct European laboratories. Reductions of SNAP-25 levels were associated with a moderate hyperactivity, which disappeared in the adult animals, and with impaired associative learning and memory. Electroencephalographic recordings revealed the occurrence of frequent spikes, suggesting a diffuse network hyperexcitability. Consistently, SNAP-25(+/-) mice displayed higher susceptibility to kainate-induced seizures, paralleled by degeneration of hilar neurons. Notably, both EEG profile and cognitive defects were improved by antiepileptic drugs. These results indicate that reduction of SNAP-25 expression is associated to generation of epileptiform discharges and cognitive dysfunctions, which can be effectively treated by antiepileptic drugs.

  5. Antiepileptic drugs with histone deacetylase inhibition activity and prostate cancer risk: a population-based case-control study.

    PubMed

    Salminen, Jukka K; Tammela, Teuvo L J; Auvinen, Anssi; Murtola, Teemu J

    2016-05-01

    Previous studies suggest that antiepileptic drugs with histone deacetylase (HDAC) inhibitor properties may have prostate cancer preventive effects. We evaluated the association between antiepileptic drug use and prostate cancer risk in a population-based case-control study. The study included all new prostate cancer cases diagnosed in Finland in 1995-2002 and matched controls (24,657 case-control pairs) identified from the Finnish Cancer Registry and the Population Register Center, respectively. Information on antiepileptic drug purchases was obtained from the national prescription reimbursement database. Odds ratios and their 95 % confidence intervals were estimated using age-adjusted and multivariable-adjusted conditional logistic regression analysis. Compared to never-users of antiepileptic drugs, the overall prostate cancer risk was decreased among users of phenobarbital, carbamazepine, and valproic acid (multivariable-adjusted odds ratio (OR) 0.47, 95 % CI 0.24-0.92; OR 0.82, 95 % CI 0.71-0.94, and OR 0.62, 95 % CI 0.42-0.92, respectively), but not among users of other antiepileptic drugs. Overall prostate cancer risk decreased in a dose-dependent manner by cumulative amount, duration and yearly dosage (intensity) of HDAC inhibitors valproic acid and carbamazepine. The risk of advanced prostate cancer was decreased only among carbamazepine users (OR 0.65, 95 % CI 0.44-0.96). Our results support possible prostate cancer preventive effects of HDAC inhibitors. However, also phenobarbital use was associated with decreased prostate cancer risk, despite not having HDAC inhibiting activity. The mechanism of action for antiepileptic drugs in prostate cancer deserves further study. PMID:27038166

  6. Quantification of sewer exfiltration using the anti-epileptic drug carbamazepine as marker species for wastewater.

    PubMed

    Fenz, R; Blaschke, A P; Clara, M; Kroiss, H; Mascher, D; Zessner, M

    2005-01-01

    The anti-epileptic drug carbamazepine was used as marker species in wastewater to identify and quantify sewer exfiltration. In several studies carbamazepine turned out to be hardly removed in wastewater treatment and not or just slightly attenuated during bank infiltration. Concentrations in wastewater are generally 1000 times higher than the limit of quantification. In contrast to many other marker species a "young" drug as carbamazepine is discharged to the environment only by wastewater. The results from this study carried out in Linz, Austria indicate an average exfiltration rate, expressed as percentage of the dry weather flow that is lost on the city-wide scale, of 1%. This rate is lower than sewage losses reported in most other studies which attempted to quantify exfiltration on the basis of groundwater pollution. However, it was also possible to identify one area with significant higher sewage losses.

  7. Successful treatment of POLG-related mitochondrial epilepsy with antiepileptic drugs and low glycaemic index diet.

    PubMed

    Martikainen, Mika H; Päivärinta, Markku; Jääskeläinen, Satu; Majamaa, Kari

    2012-12-01

    Epilepsy is a common manifestation of mitochondrial disease associated with mutations of the mitochondrial polymerase γ (POLG). Prognosis of mitochondrial epilepsy is often poor and there are few reports of successful treatment of POLG-related epilepsy. We describe a 26-year-old woman who experienced severe headache during a three-day period, followed by symptoms of visual flashing, speech difficulty, and generalised seizures. EEG recording showed non-convulsive status epilepticus (left occipital area) and brain MRI revealed parieto-occipital T2-hyperintensities. Visual aura and aphasia persisted despite antiepileptic medication with phenytoin, oxcarbazepine, and levetiracetam. Mitochondrial disorder was clinically suspected and a homozygous c.2243G>C mutation (p.Trp748Ser) was discovered in the POLG1 gene. The patient was then set on a low glycaemic index treatment (LGIT) variant of the ketogenic diet, after which the headaches, aphasia, and visual aura progressively improved and disappeared. She returned home two weeks after onset of symptoms and has not had further seizures. She continues to receive levetiracetam monotherapy and LGIT. We conclude that, at least for this patient, the combination of three antiepileptic drugs and LGIT is effective and well tolerated as treatment for severe episodes of POLG-related mitochondrial epilepsy.

  8. The Portland Neurotoxicity Scale: Validation of a Brief Self-Report Measure of Antiepileptic-Drug-Related Neurotoxicity

    ERIC Educational Resources Information Center

    Salinsky, Martin C.; Storzbach, Daniel

    2005-01-01

    The Portland Neurotoxicity Scale (PNS) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs (AEDs). The authors present data on the validity of this scale, particularly when used in longitudinal studies. Participants included 55 healthy controls, 23 epilepsy patient controls, and 86…

  9. Medical management of refractory epilepsy--practical treatment with novel antiepileptic drugs.

    PubMed

    Ben-Menachem, Elinor

    2014-01-01

    The ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review. PMID:24400690

  10. Patients' preferences for treatment outcomes of add-on antiepileptic drugs: a conjoint analysis.

    PubMed

    Manjunath, Ranjani; Yang, Jui-Chen; Ettinger, Alan B

    2012-08-01

    To understand the relative importance of the outcomes of add-on antiepileptic drugs (AEDs) and the willingness of patients with epilepsy to accept therapeutic trade-offs between seizure control and tolerability, we administered a Web-enabled, choice-format conjoint survey to patients with a self-reported physician diagnosis of epilepsy and symptoms of partial seizures. Patients answered nine choice questions to evaluate treatment outcomes of two different hypothetical add-on AEDs. Patients were first asked to choose the better of the two medicines and then asked a follow-up question about whether or not they would add the selected AED to their current treatment regimen. Our study demonstrated that patients with epilepsy consider seizure reduction to be the top priority when ranking it against the reduction or elimination of side effects. This study aids in better understanding of patients' AED treatment preferences and may aid in management of epilepsy.

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

    PubMed

    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

  12. Postpartum depression in women with epilepsy: Influence of antiepileptic drugs in a prospective study

    PubMed Central

    Galanti, Melanie; Newport, D. Jeffrey; Pennell, Page B.; Titchner, Denicia; Newman, Melanee; Knight, Bettina T.; Stowe, Zachary N.

    2013-01-01

    Patients with epilepsy are at high risk for major depressive disorder (MDD) and, according to one report, postpartum depression (PPD) as well. The study described here sought to determine the prevalence and risk factors for PPD among women with epilepsy. Fifty-six women with epilepsy participating in a prospective study of perinatal antiepileptic drug (AED) pharmacokinetics were included. Participants completed the Beck Depression Inventory (BDI) during pregnancy and the postpartum period. Fourteen participants (25.0%) had a postnatal BDI score ≥12 indicative of PPD. Logistic regression indicated that significant risk factors for PPD among women with epilepsy included multiparity (odds ratio = 12.5) and AED polytherapy (odds ratio = 9.3). The rate of PPD was unaffected by the use of specific AEDs. In conclusion, PPD rates are higher among women with epilepsy than the general population, particularly those who are multiparous or receiving AED polytherapy, and there is no evidence that AED selection modifies this risk. PMID:19854113

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

    PubMed Central

    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

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

    PubMed

    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

  15. Are there potential problems with generic substitution of antiepileptic drugs? A review of issues.

    PubMed

    Crawford, P; Feely, M; Guberman, A; Kramer, G

    2006-04-01

    In response to increasing cost pressures, healthcare systems are encouraging the use of generic medicines. This review explores potential problems with generic substitution of antiepileptic drugs (AEDs). A broad search strategy identified approximately 70 relevant articles. Potential problems with generic substitution included: The limited evidence (mainly case reports with some pharmacokinetic studies) appears to support these concerns for older AEDs. As a result, restrictions on use of specific generic AEDs are in place in some countries and recommended by some lay epilepsy organisations. As more AEDs lose patent protection, it is important to examine the question of whether generic substitution may pose problems for patients with epilepsy, and whether there should be safeguards to ensure that both physician and patient are informed when generic substitution occurs.

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

    PubMed

    Galindo-Mendez, Brahyan; Mayor, Luis C; Velandia-Hurtado, Fernando; Calderon-Ospina, Carlos

    2015-01-01

    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. PMID:26101746

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

    PubMed Central

    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. PMID:26664367

  18. Seizure control and pharmacokinetics of antiepileptic drugs in pregnant women with epilepsy.

    PubMed

    Brodtkorb, Eylert; Reimers, Arne

    2008-03-01

    The main concerns associated with epilepsy during pregnancy consist of maternal and fetal risks from uncontrolled seizures, and harmful effects of the treatment on the development of the offspring. Although seizure control is maintained in the majority, worsening occurs in a fraction of childbearing women with epilepsy. As multiple factors associated with pregnancy may have a negative impact on epilepsy, a careful analysis of the situation should be performed in those who deteriorate. Emotional and behavioural influence, including insufficient sleep and treatment non-compliance, as well as physical factors, such as emesis and pelvic distortion, should receive attention. The serum concentrations of almost all antiepileptic drugs decrease during pregnancy, particularly those which are metabolised by glucuronidation. The inter-individual variability is pronounced. In highly protein-bound drugs, such as phenytoin and valproate, unbound drug is less affected than total concentrations. Lamotrigine and levetiracetam concentrations may decrease by more than 50% in the course of pregnancy; monohydroxyoxcarbazepine by up to 30-40%. Appropriate clinical follow-up tailored to individual needs and supported by therapeutic drug monitoring should be performed in pregnant women with epilepsy. Education concerning reproductive issues is an essential part of the epilepsy service to fertile women.

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

    PubMed

    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

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

    PubMed

    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.

  1. Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs.

    PubMed

    Stöllberger, Claudia; Finsterer, Josef

    2016-10-01

    Atrial fibrillation (AF) is a frequent cause of stroke. Secondary prophylaxis by oral anticoagulants (OAC) is recommended after stroke in AF-patients. OAC can be achieved by vitamin-K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran, rivaroxaban, apixaban or edoxaban. Seizures are frequent after stroke, and antiepileptic drugs (AEDs) are indicated. The review, based on a literature research, aims to give an overview about pharmacokinetic knowledge and clinical data about drug-drug interactions (DDIs) between NOACs and AED. Carbamazepine, levetiracetam, phenobarbital, phenytoin and valproic acid might decrease the effect of NOACs by inducing P-glycoprotein (P-gp) activity. Carbamazepine, oxcarbazepine, phenytoin, phenobarbital and topiramate might decrease the effect of NOACs by inducing CYP3A4 activity. Controversial data - inhibition as well as induction of CYP3A4 - were found about valproic acid. The relevance of these DDIs is largely unknown since there are only sporadic case reports available. To increase the knowledge about DDIs between NOACs and AEDs we suggest subgroup analyses addressing effects and safety of VKAs versus NOACs in patients with AF on AEDs, in case they have been included in previously completed or still ongoing trials or registries. This could be easily feasible and would be desirable in view of the large data already accumulated. PMID:27450623

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

    PubMed Central

    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 < 0.0001) in patients on long-term therapy with conventional antiepileptic agents than in the control group. No significant change in thyroid 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. PMID:27512707

  3. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety?

    PubMed

    French, Jacqueline A; Gazzola, Deana M

    2011-08-01

    Over the last two decades a total of 11 antiepileptic drugs (AEDs) have been introduced to the US market. Randomized, placebo-controlled trials have yielded information about each drug's efficacy, tolerability, and safety profile; however, few studies have compared the newer generation AEDs directly with the older generation. Comparative studies are not always straightforward in their interpretation, as many characteristics of drugs, both favorable and unfavorable, may not be highlighted by such studies. In general, findings from the literature suggest that the newer generation AEDs (including vigabatrin, felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, zonisamide, pregabalin, rufinamide, and lacosamide) enjoy both improved tolerability and safety compared with older agents such as phenobarbital, phenytoin, carbamazepine, and valproate. This is partially supported by some of the findings of the QSS and the TTA Committee of the American Academy of Neurology (AAN), whose review of four AEDs (gabapentin, lamotrigine, topiramate, and tiagabine) is discussed. Briefly, when compared with carbamazepine, lamotrigine was better tolerated; topiramate adverse events (AEs) were fairly comparable to carbamazepine and valproate; and tiagabine compared with placebo was associated with a higher discontinuation rate due to AEs. The findings of the SANAD trial are also presented; when administered to patients with partial epilepsy, carbamazepine was most likely to fail due to AEs, and lamotrigine and gabapentin were least likely to fail due to AEs. When administered to patients with idiopathic generalized epilepsy, topiramate was most frequently associated with AE-related discontinuation, followed by valproate; and while valproate was the most efficacious drug in this arm of the study, lamotrigine was more tolerable. What makes the SANAD study valuable and somewhat unique is its head-to-head comparison of one drug with another. Such

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

    PubMed Central

    Ma, Aimei; Wang, Cuicui; Chen, Yinghui; Yuan, Weien

    2013-01-01

    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. PMID:24348021

  5. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety?

    PubMed Central

    Gazzola, Deana M.

    2011-01-01

    Over the last two decades a total of 11 antiepileptic drugs (AEDs) have been introduced to the US market. Randomized, placebo-controlled trials have yielded information about each drug’s efficacy, tolerability, and safety profile; however, few studies have compared the newer generation AEDs directly with the older generation. Comparative studies are not always straightforward in their interpretation, as many characteristics of drugs, both favorable and unfavorable, may not be highlighted by such studies. In general, findings from the literature suggest that the newer generation AEDs (including vigabatrin, felbamate, gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, zonisamide, pregabalin, rufinamide, and lacosamide) enjoy both improved tolerability and safety compared with older agents such as phenobarbital, phenytoin, carbamazepine, and valproate. This is partially supported by some of the findings of the QSS and the TTA Committee of the American Academy of Neurology (AAN), whose review of four AEDs (gabapentin, lamotrigine, topiramate, and tiagabine) is discussed. Briefly, when compared with carbamazepine, lamotrigine was better tolerated; topiramate adverse events (AEs) were fairly comparable to carbamazepine and valproate; and tiagabine compared with placebo was associated with a higher discontinuation rate due to AEs. The findings of the SANAD trial are also presented; when administered to patients with partial epilepsy, carbamazepine was most likely to fail due to AEs, and lamotrigine and gabapentin were least likely to fail due to AEs. When administered to patients with idiopathic generalized epilepsy, topiramate was most frequently associated with AE-related discontinuation, followed by valproate; and while valproate was the most efficacious drug in this arm of the study, lamotrigine was more tolerable. What makes the SANAD study valuable and somewhat unique is its head-to-head comparison of one drug with another. Such

  6. Selecting anti-epileptic drugs: a pediatric epileptologist’s view, a computer’s view

    PubMed Central

    Pestian, J; Matykiewicz, P; Holland-Bouley, K; Standridge, S; Spencer, M; Glauser, T

    2012-01-01

    Objective To identify which clinical characteristics are important to include in clinical decision support systems developed for Antiepileptic Drug (AEDs) selection. Methods Twenty-three epileptologists from the Childhood Absence Epilepsy network completed a survey related to AED selection. Using cluster analysis their responses where classified into subject matter groups and weighted for importance. Results Five distinct subject matter groups were identified and their relative weighting for importance were determined: disease characteristics (weight 4.8 ± 0.049), drug toxicities (3.82 ± 0.098), medical history (3.12 ± 0.102), systemic characteristics (2.57 ± 0.048) and genetic characteristics (1.08 ± 0.046). Conclusion Research about prescribing patterns exists but research on how such data can be used to train advanced technology is novel. As machine learning algorithms becomes more and more prevalent in clinical decisions support systems, developing methods for determining which data should be part of those algorithms is equally important. PMID:22998126

  7. Risk of recurrence after discontinuation of antiepileptic drug therapy in children with epilepsy

    PubMed Central

    Incecik, Faruk; Herguner, Ozlem M.; Altunbasak, Sakir; Mert, Gulen; Kiris, Nurcihan

    2014-01-01

    Objectives: The numerous antiepileptic drug (AED) withdrawal studies published in the last 40 years have relied mainly on heterogeneous study groups. There is still no general agreement on the criteria to predict safe discontinuation. The goal of this study was to assess the outcome of AED withdrawal in epileptic children. Materials and Methods: Three hundred and eight children with epilepsy were enrolled, and these patients followed at least 1 year after drug withdrawal. Time to seizure relapse and predictive factors were analyzed by survival methods. Results: Among the 308 patients, 179 (58.1%) were boys and 129 (41.9%) were girls and the mean age at the seizure onset was 60.41 ± 36.54 months (2-144 months). The recurrence occurred in 73 (23.7%) patients. Mental retardation, history of febrile seizure, etiological of epilepsy, abnormal first electroencephalogram (EEG), abnormal neuroimaging findings, and total number of AED before remission were significantly associated with relapse risk according to univariate analysis. In the multivariate analysis, abnormal first EEG and number of AED before remission (polytherapy) were the risk factors influencing seizure recurrence. Conclusions: In our study, recurrence rate was 23.7% in children and most occurred during the 1st year. The potential risk factors of recurrence are history of febrile seizure, mental retardation, etiological of epilepsy, abnormal first EEG, abnormal neuroimaging findings, and total number of AED before remission. However, we found abnormal first EEG and polytherapy as risk factors of recurrence in multivariate analysis. PMID:25250060

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

    PubMed

    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.

  9. The antiepileptic drug diphenylhydantoin affects the structure of the human erythrocyte membrane.

    PubMed

    Suwalsky, Mario; Mennickent, Sigrid; Norris, Beryl; Villena, Fernando; Cuevas, Francisco; Sotomayor, Carlos P

    2004-01-01

    Phenytoin (diphenylhydantoin) is an antiepileptic agent effective against all types of partial and tonic-clonic seizures. Phenytoin limits the repetitive firing of action potentials evoked by a sustained depolarization of mouse spinal cord neurons maintained in vitro. This effect is mediated by a slowing of the rate of recovery of voltage activated Na+ channels from inactivation. For this reasons it was thought of interest to study the binding affinities of phenytoin with cell membranes and their perturbing effects upon membrane structures. The effects of phenytoin on the human erythrocyte membrane and molecular models have been investigated in the present work. This report presents the following evidence that phenytoin interacts with cell membranes: a) X-ray diffraction and fluorescence spectroscopy of phospholipid bilayers showed that phenytoin perturbed a class of lipids found in the outer moiety of cell membranes; b) in isolated unsealed human erythrocyte membranes (IUM) the drug induced a disordering effect on the polar head groups and acyl chains of the erythrocyte membrane lipid bilayer; c) in scanning electron microscopy (SEM) studies on human erythrocytes the formation of echinocytes was observed, due to the insertion of phenytoin in the outer monolayer of the red cell membrane. This is the first time that an effect of phenytoin on the red cell shape is described. However, the effects of the drug were observed at concentrations higher than those currently found in plasma when phenytoin is therapeutically administered. PMID:18998414

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

    PubMed Central

    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 neurodevelopmental effects exist across four commonly used antiepileptic drugs (AEDs). Here, we examined the relationship of IQ and education in both parents to child IQ at age 3 years. IQ and education for both parents were statistically correlated to child IQ. However, paternal IQ and education were not significant after accounting for maternal IQ effects. Because maternal IQ and education are independently related to child cognitive outcome, both should be assessed in studies investigating the effects of fetal drug exposures or other environmental factors that could affect the child’s cognitive outcome. PMID:21546316

  11. Dried blood spots for monitoring and individualization of antiepileptic drug treatment.

    PubMed

    Milosheska, Daniela; Grabnar, Iztok; Vovk, Tomaž

    2015-07-30

    Therapeutic drug monitoring (TDM) is a multi-disciplinary clinical specialty used for optimization and individualization of drug therapy in the general and special populations. Since most antiepileptic drugs (AEDs) are characterized by pronounced intra- and inter-individual variability, it can be especially valuable as an aid for dosing adjustments in patients with epilepsy. Dried blood spots (DBS) sampling technique is recognized as a suitable alternative for conventional sampling methods as TDM interventions should be applied in the most cost-effective, rational and clinically useful manner. In the present review we summarize the latest trends and applications of DBS in TDM of epilepsy. Quantification of AEDs in DBS was employed in various clinical settings and has been already reported for phenobarbital, phenytoin, valproic acid, clonazepam, clobazam, carbamazepine, topiramate, rufinamide, lamotrigine, 10-hydroxycarbazepine and levetiracetam. The major limitation of the published studies are restricted evaluation of critical parameters such as the impact of spotted blood volume, spot homogeneity and haematocrit effect, limited clinical validation and non-established correlations between the DBS and plasma concentrations of AEDs. Standardization of critical technical aspects for appropriate sampling, sample preparation and validation of the analytical procedures for quantification of the drugs, as well as appropriate interpretation of the results are the fields which should get more attention in upcoming studies. Limited data on clinical validation and the fact that this technique has been used in practice only for a few AEDs makes the routine implementation of TDM of AEDs using DBS method a big challenge that should be faced by the pharmaceutical scientists in the future. PMID:25896371

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

    PubMed

    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

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

    PubMed Central

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

    2013-01-01

    Summary Background Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. Methods In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. Findings We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94–101) than to carbamazepine (105, 102–108; p=0·0015), lamotrigine (108, 105–110; p=0·0003), or phenytoin (108, 104–112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=−0·56, p<0·0001), verbal ability (r=−0·40, p=0·0045), non-verbal ability (r=−0·42, p=0·0028), memory (r=−0·30, p=0·0434), and executive function (r=−0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ

  14. Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

    PubMed Central

    Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Hyun; Jun, Min-Young

    2011-01-01

    Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring. PMID:21660146

  15. The safety and tolerability of newer antiepileptic drugs in children and adolescents.

    PubMed

    Kayani, Saima; Sirsi, Deepa

    2012-01-01

    Childhood epilepsy continues to be intractable in more than 25% of patients diagnosed with epilepsy. The introduction of new anti-epileptic drugs (AEDs) provides more options for treatment of children with epilepsy. We review the safety and tolerability of seven new AEDs (levetiracetam, lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin and zonisamide) focusing on their side effect profiles and safety in children and adolescents. Many considerations that are specific for children such as the impact of AEDs on the developing brain are not addressed during the development of new AEDs. They are usually approved as adjunctive therapies based upon clinical trials involving adult patients with partial epilepsy. However, 2 of the AEDs reviewed here (rufinamide and vigabatrin) have FDA approval in the U.S. for specific Pediatric epilepsy syndromes, which are discussed below. The Pediatrician or Neurologists decision on the use of a new AED is an evolutionary process largely dependent on the patient characteristics, personal/peer experiences and literature about efficacy and safety profiles of these medications. Evidence based guidelines are limited due to a lack of randomized controlled trials involving pediatric patients for many of these new AEDs. PMID:23650467

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    McCorry, D; Bromley, R

    2015-05-01

    A clinical scenario of a young female on 800 mg of sodium valproate (VPA) who has recently failed lamotrigine (LTG) and levetiracetam (LEV) and who is currently planning a pregnancy is presented. Currently available data pertaining to the longer-term development of children exposed to antiepileptic drugs (AEDs) are reviewed along with considerations around the methodology and interpretation of such research. There is an accumulation of data highlighting significant risks associated with prenatal exposed to VPA, with the level of risk being mediated by dose. The majority of published evidence does not find a significant risk associated with carbamazepine (CBZ) exposure in utero for global cognitive abilities however the evidence for more specific cognitive skills are unclear. Limited data indicate that LTG may be a preferred treatment to VPA in terms of foetal outcome but further evidence is required. Too little data pertaining to LEV exposure is available and a lack of evidence regarding risk of this and other new AEDs should not be interpreted as evidence of safety. PMID:25819874

  19. Effects of pharmaceuticals on aquatic invertebrates. Part I. The antiepileptic drug carbamazepine.

    PubMed

    Oetken, M; Nentwig, G; Löffler, D; Ternes, T; Oehlmann, J

    2005-10-01

    The effects of the antiepileptic drug carbamazepine (CBZ) were studied in three freshwater invertebrate species representing different taxonomic groups, life histories, and habitats in aquatic ecosystems. The oligochaete Lumbriculus variegatus was exposed by way of CBZ-spiked sediments at nominal concentrations between 0.625 and 10 mg/kg dry weight (dw) for 28 days. At the end of the test, reproduction and biomass were monitored as end points. The non-biting midge Chironomus riparius was exposed to CBZ in a series of tests at nominal CBZ concentrations in sediment ranging from 0.16 to 100 mg/kg dw at 20 degrees C and 23 degrees C. Emergence and gender ratio were monitored at the end of the test. The freshwater snail Potamopyrgus antipodarum as the third test species was used in a chronic reproduction test for 28 days at aqueous CBZ concentrations from 0.4 to 250 mg/L. Whereas for the oligochaete and the snail no effects were observed, C. riparius exhibited a significant and concentration-dependent decrease of emergence in all test series. No observed effect concentrations and 10% effect concentrations were in the range of 33 to 140 and 70 to 210 microg/kg dw, respectively, based on measured CBZ concentrations in sediments. These low values indicate that CBZ may pose a potential threat for the survival of C. riparius and probably also for other aquatic insect populations in the field.

  20. Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII).

    PubMed

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

    2015-03-01

    The Twelfth Eilat Conference on New Antiepileptic Drugs (AEDs) - EILAT XII, took place in Madrid, Spain from August 31st to September 3rd 2014. About 130 basic scientists, clinical pharmacologists and neurologists from 22 countries attended the conference, whose main themes included "Conquering pharmacoresistant epilepsy", "Innovative emergency treatments", "Progress report on second-generation treatment" and "New methods and formulations". 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 2004. Like the EILAT X and EILAT XI reports, the current article focuses on the preclinical and clinical pharmacology of AEDs that are currently in development. These include adenosine-releasing silk, allopregnanolone (SAGE-547), AMP-X-0079, brivaracetam, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-glucose, everolimus, ganaxolone, huperzine A, imepitoin, minocycline, NAX 801-2, pitolisant, PRX 0023, SAGE-217, valnoctamide and its homologue sec-butyl-propylacetamide (SPD), and VLB-01. Since the previous Eilat conference, perampanel has been introduced into the market and twelve novel potential epilepsy treatments are presented for the first time. PMID:25769377

  1. Medicine possession ratio as proxy for adherence to antiepileptic drugs: prevalence, associations, and cost implications

    PubMed Central

    Jacobs, Karen; Julyan, Marlene; Lubbe, Martie S; Burger, Johanita R; Cockeran, Marike

    2016-01-01

    Objective To determine the adherence status to antiepileptic drugs (AEDs) among epilepsy patients; to observe the association between adherence status and age, sex, active ingredient prescribed, treatment period, and number of comorbidities; and to determine the effect of nonadherence on direct medicine treatment cost of AEDs. Methods A retrospective study analyzing medicine claims data obtained from a South African pharmaceutical benefit management company was performed. Patients of all ages (N=19,168), who received more than one prescription for an AED, were observed from 2008 to 2013. The modified medicine possession ratio (MPRm) was used as proxy to determine the adherence status to AED treatment. The MPRm was considered acceptable (adherent) if the calculated value was ≥80%, but ≤110%, whereas an MPRm of <80% (unacceptably low) or >110% (unacceptably high) was considered nonadherent. Direct medicine treatment cost was calculated by summing the medical scheme contribution and patient co-payment associated with each AED prescription. Results Only 55% of AEDs prescribed to 19,168 patients during the study period had an acceptable MPRm. MPRm categories depended on the treatment period (P>0.0001; Cramer’s V=0.208) but were independent of sex (P<0.182; Cramer’s V=0.009). Age group (P<0.0001; Cramer’s V=0.067), active ingredient (P<0.0001; Cramer’s V=0.071), and number of comor-bidities (P<0.0001; Cramer’s V=0.050) were statistically but not practically significantly associated with MPRm categories. AEDs with an unacceptably high MPRm contributed to 3.74% (US$736,376.23) of the total direct cost of all AEDs included in the study, whereas those with an unacceptably low MPRm amounted to US$3,227,894.85 (16.38%). Conclusion Nonadherence to antiepileptic treatment is a major problem, encompassing ~20% of cost in our study. Adherence, however, is likely to improve with the treatment period. Further research is needed to determine the factors influencing

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

    SciTech Connect

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

    1982-02-01

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

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

    PubMed

    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 < 0.001) and to healthy controls (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 < 0.001) and healthy controls (P < 0.001), and a higher 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.

  4. Comparative study of lacosamide and classical sodium channel blocking antiepileptic drugs on sodium channel slow inactivation.

    PubMed

    Niespodziany, Isabelle; Leclère, Nathalie; Vandenplas, Catherine; Foerch, Patrik; Wolff, Christian

    2013-03-01

    Many antiepileptic drugs (AEDs) exert their therapeutic activity by modifying the inactivation properties of voltage-gated sodium (Na(v) ) channels. Lacosamide is unique among AEDs in that it selectively enhances the slow inactivation component. Although numerous studies have investigated the effects of AEDs on Na(v) channel inactivation, a direct comparison of results cannot be made because of varying experimental conditions. In this study, the effects of different AEDs on Na(v) channel steady-state slow inactivation were investigated under identical experimental conditions using whole-cell patch-clamp in N1E-115 mouse neuroblastoma cells. All drugs were tested at 100 μM, and results were compared with those from time-matched control groups. Lacosamide significantly shifted the voltage dependence of Na(v) current (I(Na) ) slow inactivation toward more hyperpolarized potentials (by -33 ± 7 mV), whereas the maximal fraction of slow inactivated channels and the curve slope did not differ significantly. Neither SPM6953 (lacosamide inactive enantiomer), nor carbamazepine, nor zonisamide affected the voltage dependence of I(Na) slow inactivation, the maximal fraction of slow inactivated channels, or the curve slope. Phenytoin significantly increased the maximal fraction of slow inactivated channels (by 28% ± 9%) in a voltage-independent manner but did not affect the curve slope. Lamotrigine slightly increased the fraction of inactivated currents (by 15% ± 4%) and widened the range of the slow inactivation voltage dependence. Lamotrigine and rufinamide induced weak, but significant, shifts of I(Na) slow inactivation toward more depolarized potentials. The effects of lacosamide on Na(v) channel slow inactivation corroborate previous observations that lacosamide has a unique mode of action among AEDs that act on Na(v) channels. PMID:23239147

  5. Antiepileptic drug treatment of rolandic epilepsy and Panayiotopoulos syndrome: clinical practice survey and clinical trial feasibility

    PubMed Central

    Mellish, Louise C; Dunkley, Colin; Ferrie, Colin D; Pal, Deb K

    2015-01-01

    Background The evidence base for management of childhood epilepsy is poor, especially for the most common specific syndromes such as rolandic epilepsy (RE) and Panayiotopoulos syndrome (PS). Considerable international variation in management and controversy about non-treatment indicate the need for high quality randomised controlled trials (RCT). The aim of this study is, therefore, to describe current UK practice and explore the feasibility of different RCT designs for RE and PS. Methods We conducted an online survey of 590 UK paediatricians who treat epilepsy. Thirty-two questions covered annual caseload, investigation and management practice, factors influencing treatment, antiepileptic drug preferences and hypothetical trial design preferences. Results 132 responded (22%): 81% were paediatricians and 95% at consultant seniority. We estimated, annually, 751 new RE cases and 233 PS cases. Electroencephalography (EEG) is requested at least half the time in approximately 70% of cases; MRI brain at least half the time in 40%–65% cases and neuropsychological evaluation in 7%–8%. Clinicians reported non-treatment in 40%: main reasons were low frequency of seizures and parent/child preferences. Carbamazepine is the preferred older, and levetiracetam the preferred newer, RCT arm. Approximately one-half considered active and placebo designs acceptable, choosing seizures as primary and cognitive/behavioural measures as secondary outcomes. Conclusions Management among respondents is broadly in line with national guidance, although with possible overuse of brain imaging and underuse of EEG and neuropsychological assessments. A large proportion of patients in the UK remains untreated, and clinicians seem amenable to a range of RCT designs, with carbamazepine and levetiracetam the preferred active drugs. PMID:25202134

  6. Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy

    PubMed Central

    Specchio, L; Tramacere, L; La Neve, A; Beghi, E

    2002-01-01

    Objectives: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. Methods: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. Results: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. Conclusions: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors. PMID:11784819

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

    PubMed

    Heidegger, Tonio; Krakow, Karsten; Ziemann, Ulf

    2010-10-01

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

  8. Use of antiepileptic drugs during pregnancy and lactation: Type of information provided by searching Google.

    PubMed

    Lavi-Blau, Tal; Ekstein, Dana; Neufeld, Miri Y; Eyal, Sara

    2016-02-01

    Surveys among women with epilepsy (WWE) show that they receive their essential pregnancy-related information from many sources, including the internet. Our aim was to assess the types of websites provided by searching Google for the use of four antiepileptic drugs (AEDs) during pregnancy and lactation. The search was performed on 40 computers used by health-care professionals, on 40 computers used by nonhealth-care professionals, and on 5 computers used by WWE in Israel and on 8 computers used by nonhealth-care professionals in the U.S. On each computer, a Google search was conducted for term combinations that included one AED name ("carbamazepine","valproic acid", "lamotrigine", "levetiracetam", or "Keppra") and "Pregnancy", "Lactation", or "Breastfeeding". The top three and top ten websites retrieved in every search were mapped (a total of 45 and 150 websites, respectively, from each computer). Across all searches in English, on both U.S. and Israeli computers, the majority of websites listed among the first three and first ten results were those of independent health portals. The representation of the Epilepsy Foundation website was 10% or less, and only a few results were obtained from the NIH's general public-oriented MedlinePlus. In Hebrew, results included almost exclusively Israeli or Hebrew-translated websites. As in English, results from public-oriented, professionally-written websites in Hebrew accounted for less than 50% of entries. Overall, the availability of readable and high-quality information on AEDs used by pregnant and breastfeeding women is limited. Guiding patients towards accurate web resources can help them navigate among the huge amount of available online information. PMID:26773680

  9. Association of Interictal Epileptiform Discharges with Sleep and Anti-Epileptic Drugs

    PubMed Central

    Mohan, Latika; Singh, Jayvardhan; Singh, Yogesh; Kathrotia, Rajesh; Goel, Arun

    2016-01-01

    Background The presence of interictal epileptiform discharges (IEDs) in electroencephalogram (EEG) is diagnostic of epilepsy. Latent IEDs are activated during sleep. Anti-epileptic drugs (AEDs) improve sleep. AEDs, sleep, and IEDs may interact and affect epilepsy management. Purpose To explore the occurrence of IEDs and its association with sleep and AED status in suspected patients of epilepsy. Methods EEG records were collected of suspected patients of epilepsy who reported to the electrophysiology laboratory of a tertiary care hospital during 1 year. The anthropometric details, clinical presentations, and AED status of the patients were recorded from the EEG records. Patients were divided into 2 categories based on whether AEDs had been started prior to the EEG evaluation (category-I) or not (category-II). The occurrences of IEDs in EEG recordings in both categories were analyzed. Results In 1 year, 138 patients were referred for diagnostic EEG evaluation. One-hundred-two patients fulfilled the inclusion criteria, of which 57 patients (53%) belonged to category-I and 45 patients (47%) belonged to category-II. Incidence of IEDs, suggestive of definite diagnosis of epilepsy in category-I was 88% and in category-II was 69%, and this difference was statistically significant (p = 0.02). Conclusion The increased proportion of IEDs in category-I patients may be due to high clinical suspicion or compounding interaction of AEDs and sleep. More extensive studies are required to delineate the complex interaction of AEDs, sleep, and IEDs so that judicious yet prompt management of epilepsy can be carried out. PMID:27780990

  10. Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS

    PubMed Central

    Birbeck, G.L.; French, J.A.; Perucca, E.; Simpson, D.M.; Fraimow, H.; George, J.M.; Okulicz, J.F.; Clifford, D.B.; Hachad, H.; Levy, R.H.

    2012-01-01

    Objective: To develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. Methods: The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. Results and Recommendations: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of ∼50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of ∼50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C). PMID:22218281

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

    PubMed

    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.

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

    PubMed

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

    2016-08-01

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

  13. Use of antiepileptic drugs during pregnancy and lactation: Type of information provided by searching Google.

    PubMed

    Lavi-Blau, Tal; Ekstein, Dana; Neufeld, Miri Y; Eyal, Sara

    2016-02-01

    Surveys among women with epilepsy (WWE) show that they receive their essential pregnancy-related information from many sources, including the internet. Our aim was to assess the types of websites provided by searching Google for the use of four antiepileptic drugs (AEDs) during pregnancy and lactation. The search was performed on 40 computers used by health-care professionals, on 40 computers used by nonhealth-care professionals, and on 5 computers used by WWE in Israel and on 8 computers used by nonhealth-care professionals in the U.S. On each computer, a Google search was conducted for term combinations that included one AED name ("carbamazepine","valproic acid", "lamotrigine", "levetiracetam", or "Keppra") and "Pregnancy", "Lactation", or "Breastfeeding". The top three and top ten websites retrieved in every search were mapped (a total of 45 and 150 websites, respectively, from each computer). Across all searches in English, on both U.S. and Israeli computers, the majority of websites listed among the first three and first ten results were those of independent health portals. The representation of the Epilepsy Foundation website was 10% or less, and only a few results were obtained from the NIH's general public-oriented MedlinePlus. In Hebrew, results included almost exclusively Israeli or Hebrew-translated websites. As in English, results from public-oriented, professionally-written websites in Hebrew accounted for less than 50% of entries. Overall, the availability of readable and high-quality information on AEDs used by pregnant and breastfeeding women is limited. Guiding patients towards accurate web resources can help them navigate among the huge amount of available online information.

  14. Outcomes in Postoperative Pediatric Cardiac Surgical Patients Who Received an Antiepileptic Drug

    PubMed Central

    Dinh, Kimberly L.; McDade, Erin J.; Moffett, Brady S.; Wilfong, Angus A.; Cabrera, Antonio G.

    2016-01-01

    BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post–cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical patients initiated on phenobarbital, phenytoin, and levetiracetam were queried. Patients were excluded if the AED was not initiated on the admission for surgery. Patients who received 1 AED were compared to patients who received 2 AED, and differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS: A total of 37 patients met the study criteria. Patients were initiated on an AED a median of 4 days following surgery and became seizure free a median of 1 day after initiation, with 65% remaining seizure free after the first dose. Half of all patients required 2 AEDs for seizure control, with a higher proportion of adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam. CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work is necessary to evaluate long-term neurodevelopmental outcomes in this population and whether outcomes are a result of the AED or of other clinical sequelae.

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

    PubMed Central

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

    2016-01-01

    Background & objectives: Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs. Methods: The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed. Results: Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, P<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (P<0.01). Interpretation & conclusions: The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701). PMID:27241646

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    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 (P<0.05). The proportion of AED monotherapy in the autonomic seizure group and petit mal group was highest, and the proportion of two AED in combination with the psychomotor seizure, grand mal and simple partial seizure groups was highest. The serum levels of folate and vitamin B12 in these patients following treatment were significantly lower than those prior to treatment (P<0.05). The differences in the serum levels of folate and vitamin B12 in these groups following treatment were not statistically significant (P>0.05). 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

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

    PubMed Central

    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 (P<0.05). The proportion of AED monotherapy in the autonomic seizure group and petit mal group was highest, and the proportion of two AED in combination with the psychomotor seizure, grand mal and simple partial seizure groups was highest. The serum levels of folate and vitamin B12 in these patients following treatment were significantly lower than those prior to treatment (P<0.05). The differences in the serum levels of folate and vitamin B12 in these groups following treatment were not statistically significant (P>0.05). 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

  1. Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome1,2,3

    PubMed Central

    Dinday, Matthew T.

    2015-01-01

    Abstract Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and identified 4 compounds that rescued the behavioral seizure component, including 1 compound (dimethadione) that suppressed associated electrographic seizure activity. Fenfluramine, but not huperzine A, also showed antiepileptic activity in our zebrafish assays. The effectiveness of compounds that block neuronal calcium current (dimethadione) or enhance serotonin signaling (fenfluramine) in our zebrafish model suggests that these may be important therapeutic targets in patients with DS. Over 150 compounds resulting in fatality were also identified. We conclude that the combination of behavioral and electrophysiological assays provide a convenient, sensitive, and rapid basis for phenotype-based drug screening in zebrafish mimicking a genetic form of epilepsy. PMID:26465006

  2. Assessment of oral side effects of Antiepileptic drugs and traumatic oro-facial injuries encountered in Epileptic children

    PubMed Central

    Ghafoor, P A Fazal; Rafeeq, Mohammed; Dubey, Alok

    2014-01-01

    Background: Epilepsy is a chronic disorder with unpredictably recurring seizure. Uncontrolled attacks can put patients at risk of suffering oro-facial trauma. Antiepileptic drugs (AED) provide satisfactory control of seizures in most of the patients with epilepsy. However use of AED has been found to cause many side effects inclusive of side effects in the oral cavity also. Materials & Methods: This study was conducted on 150 epileptic children, who were on anti epileptic medication for one year. Results: Gingival over growth was seen as common side effect of the AED drugs. Lip and cheek biting were the most common soft tissue injury, while tooth fracture was the most common hard tissue dental injury. Conclusion: General physicians, physicians & dentists should be well aware of the potential side effects of AED. A Dentist should be well versed and trained to manage oro-facial injuries in the emergency department. How to cite the article: Ghafoor PA, Rafeeq M, Dubey A. Assessment of oral side effects of Antiepileptic drugs and traumaticoro-facial injuries encountered in Epileptic children. J Int Oral Health 2014;6(2):126-8. PMID:24876713

  3. Effect of second-generation antiepileptic drugs on diplopia: a meta-analysis of placebo-controlled studies.

    PubMed

    Han, Haiyan; Qu, Wensheng; Kang, Huicong; Hu, Xiaoqing; Zhen, Guohua; Zhu, Suiqiang; Xue, Zheng

    2012-08-01

    Different antiepileptic drugs (AEDs) may cause similar adverse effects, one of which is diplopia. However, the AEDs causing diplopia and the dose-response effect of each drug remains uncertain. In this study, we compared several second-generation AEDs to find out whether they would contribute to the risk of diplopia and their effect-causing dose. A meta-analysis was performed on 19 studies in agreement with our inclusion criteria. The results showed that eight commonly used second-generation AEDs (gabapentin, levetiracetam, oxcarbazepine, lamotrigine, pregabalin, topiramate, vigabatrin and zonisamide) could cause diplopia. The reported odds ratios (ORs) ranged from 1.406 to 7.996. Ranking risks from the highest to the lowest ORs of the eight AEDs of any dose resulted in the following order: use of oxcarbazepine (7.996), levetiracetam (7.472), lamotrigine (5.258), vigabatrin (3.562), pregabalin (3.048), topiramate (2.660), gabapentin (1.966), zonisamide (1.406). Taking into account the ORs above, we can conclude that second-generation AEDs of any dose may cause diplopia. However, the levetiracetam-caused diplopia needs to be further studied according to the data (OR, 7.472; 95% confidence interval, 0.375-148.772). These findings ask for better concerns about patients' quality of life when giving antiepileptic treatments.

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

    PubMed

    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

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

    PubMed

    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%, p<0.01). These are the first data in the literature about the within-patient variation in steady-state plasma concentrations of a series of stable treatments with brand-name AEDs in a real clinical setting. In conclusion, a significant interday variability in intrapatient LTG, LEV and TPM 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

  6. Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs.

    PubMed

    Hamed, Sherifa A

    2016-01-01

    Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

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

    PubMed

    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

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

    PubMed

    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

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

    PubMed

    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.

  10. Predictive value of isolated epileptiform discharges for a favorable therapeutic response to antiepileptic drugs in nonepileptic psychiatric patients.

    PubMed

    Boutros, Nash N; Kirollos, Sandra B; Pogarell, Oliver; Gallinat, Jürgen

    2014-02-01

    The efficacy of antiepileptic drugs (AEDs) in treating behavioral symptoms in nonepileptic psychiatric patients with abnormal EEGs is currently unknown. Although isolated epileptiform discharges have been reported in many psychiatric conditions, they are most commonly observed in patients with aggression, panic, or autistic spectrum disorders. The literature search was guided by 3 criteria: (1) studies had patients who did not experience seizures, (2) patients had EEGs, and (3) an AED was administered. Most important finding is that the number of "controlled" studies was extremely small. Overall, most reports suggest that the use of an AED can be associated with clinical and, at times, improved EEG abnormalities. Additionally, six controlled studies were found for other psychiatric disorders, such as learning disabilities with similar results. Overall, the use of anticonvulsants to treat nonepileptic psychiatric patients needs further controlled studies to better define indications, adequate EEG work-up, best AED to be used, and optimal durations of treatment attempts.

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

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed

    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.

  14. Common Variants of KCNJ10 Are Associated with Susceptibility and Anti-Epileptic Drug Resistance in Chinese Genetic Generalized Epilepsies

    PubMed Central

    Guo, Yong; Yan, Kui Po; Qu, Qiang; Qu, Jian; Chen, Zi Gui; Song, Tao; Luo, Xiang-Ying; Sun, Zhong-Yi; Bi, Chang-Long; Liu, Jin-Fang

    2015-01-01

    To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI–TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29–0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53–0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59–0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06–2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72–0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance. PMID:25874548

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

    PubMed

    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.

  16. Effects of antiepileptic drugs on learning as assessed by a repeated acquisition of response sequences task in rats.

    PubMed

    Shannon, Harlan E; Love, Patrick L

    2007-02-01

    Patients with epilepsy can have impaired cognitive abilities. Antiepileptic drugs (AEDs) may contribute to the cognitive deficits observed in patients with epilepsy, and have been shown to induce cognitive impairments in healthy individuals. However, there are few systematic data on the effects of AEDs on specific cognitive domains. We have previously demonstrated that a number of AEDs can impair working memory and attention. The purpose of the present study was to evaluate the effects of AEDs on learning as measured by a repeated acquisition of response sequences task in nonepileptic rats. The GABA-related AEDs phenobarbital and chlordiazepoxide significantly disrupted performance by shifting the learning curve to the right and increasing errors, whereas tiagabine and valproate did not. The sodium channel blockers carbamazepine and phenytoin suppressed responding at higher doses, whereas lamotrigine shifted the learning curve to the right and increased errors, and topiramate was without significant effect. Levetiracetam also shifted the learning curve to the right and increased errors. The disruptions produced by triazolam, chlordiazepoxide, lamotrigine, and levetiracetam were qualitatively similar to the effects of the muscarinic cholinergic receptor antagonist scopolamine. The present results indicate that AEDs can impair learning, but there are differences among AEDs in the magnitude of the disruption in nonepileptic rats, with drugs that enhance GABA receptor function and some that block sodium channels producing the most consistent impairment of learning. PMID:17174158

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

    PubMed

    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

  18. Effect of the Anti-depressant Sertraline, the Novel Anti-seizure Drug Vinpocetine and Several Conventional Antiepileptic Drugs on the Epileptiform EEG Activity Induced by 4-Aminopyridine.

    PubMed

    Sitges, Maria; Aldana, Blanca Irene; Reed, Ronald Charles

    2016-06-01

    Seizures are accompanied by an exacerbated activation of cerebral ion channels. 4-aminopyridine (4-AP) is a pro-convulsive agent which mechanism of action involves activation of Na(+) and Ca(2+) channels, and several antiepileptic drugs control seizures by reducing these channels permeability. The antidepressant, sertraline, and the anti-seizure drug vinpocetine are effective inhibitors of cerebral presynaptic Na(+) channels. Here the effectiveness of these compounds to prevent the epileptiform EEG activity induced by 4-AP was compared with the effectiveness of seven conventional antiepileptic drugs. For this purpose, EEG recordings before and at three intervals within the next 30 min following 4-AP (2.5 mg/kg, i.p.) were taken in anesthetized animals; and the EEG-highest peak amplitude values (HPAV) calculated. In control animals, the marked increase in the EEG-HPAV observed near 20 min following 4-AP reached its maximum at 30 min. Results show that this epileptiform EEG activity induced by 4-AP is prevented by sertraline and vinpocetine at a dose of 2.5 mg/kg, and by carbamazepine, phenytoin, lamotrigine and oxcarbazepine at a higher dose (25 mg/kg). In contrast, topiramate (25 mg/kg), valproate (100 mg/kg) and levetiracetam (100 mg/kg) failed to prevent the epileptiform EEG activity induced by 4-AP. It is concluded that 4-AP is a useful tool to elicit the mechanism of action of anti-seizure drugs at clinical meaningful doses. The particular efficacy of sertraline and vinpocetine to prevent seizures induced by 4-AP is explained by their high effectiveness to reduce brain presynaptic Na(+) and Ca(2+) channels permeability. PMID:26830290

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

    PubMed Central

    KARIMZADEH, Parvaneh; BAKRANI, Vahid

    2013-01-01

    Objective According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. Material & Methods In this descriptive study, children less than 14 years old with AED side effects referred to the Children’s Medical Center and Mofid Childeren’s Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. Results A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). Conclusion In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions. PMID:24665302

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

    PubMed Central

    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

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

    PubMed

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

    2016-01-01

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

  2. Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells.

    PubMed

    Wilson, Emma L; Garton, Mark; Fuller, Heidi R

    2016-05-01

    Phenytoin is an antiepileptic drug used in the management of partial and tonic-clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast-like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin.

  3. Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle.

    PubMed

    Meisel, Christian; Schulze-Bonhage, Andreas; Freestone, Dean; Cook, Mark James; Achermann, Peter; Plenz, Dietmar

    2015-11-24

    Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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

  8. Vitamin D in epilepsy: vitamin D levels in epilepsy patients, patients on antiepileptic drug polytherapy and drug-resistant epilepsy sufferers.

    PubMed

    Nagarjunakonda, S; Amalakanti, S; Uppala, V; Rajanala, L; Athina, S

    2016-01-01

    The objective of this study was to assess vitamin D levels in epileptic patients and to compare its serum levels in patients on antiepileptic monotherapy and polytherapy. We analyzed the serum 25-hydroxy (25-OH) vitamin D levels in 98 consecutive subjects (43 epileptic patients and 55 non-epileptics). Factors influencing its serum levels such as degree of sun exposure, physical activity and dietary intake were taken into consideration. Overall, 41% had deficient, 49% had insufficient and 9% had sufficient levels of serum vitamin D. Elderly individuals (>60 years) and people employed in offices and schools had lower blood vitamin D levels. Across both the sexes, epileptic patients and non-epileptics, epileptic patients on monotherapy and polytherapy and patients with drug-responsive and -resistant seizures, there were no significant differences in serum 25-OH vitamin D levels. Our study shows that people with epilepsy suffer with vitamin D deficiency along with their normal peers.

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

    PubMed Central

    Menon, Bindu; Ramalingam, Krishnan; Kumar, Rajendiran Vinoth

    2014-01-01

    Background: Oxidative stress has been implicated in various disorders including epilepsy. We studied the antioxidant status in patients with epilepsy and aimed at determining whether there was any difference in the antioxidant levels between patients and controls, patients who are not on antiepileptic drugs (AEDs), and on treatment, between individual AEDs and patients on monotherapy and polytherapy. Materials and Methods: Antioxidant levels like catalase, glutathione peroxidase (GPx), vitamin E, glutathione (GSH), thiol group (SH), uric acid, and total antioxidant capacity (TAC) were compared between 100 patients with epilepsy and equal number of controls. Twenty-five patients who were not on AEDs were compared with patients on AEDs and the control group. Patients were divided into monotherapy and polytherapy group and antioxidant status was compared between the two groups and between individual drugs. Results: Catalase, SH, vitamin E, and TAC were significantly low in patients with epilepsy than those in the control group (P < 0.001). GSH and uric acid did not show any difference; GPx in patients was significantly higher than those in the control group There were no differences in the antioxidant levels between the treated and the untreated groups; however, it was lower in untreated patients than controls (P < 0.001), suggesting that AEDs do not modify the oxidative stress. Patients on Valproate (VPA) showed higher catalase and GPx levels. Catalase was higher in the monotherapy than polytherapy group (P < 0.04). Conclusion: Our study found significantly low levels of antioxidant in patients as compared to controls. AED did not influence the antioxidant status suggesting that seizures induce oxidative stress. PMID:25506160

  10. Obtaining pediatric indications for new anti-epileptic drugs: how and when.

    PubMed

    Garofalo, Elizabeth

    2006-01-01

    Drug development in children poses a number of challenges that must be overcome to obtain adequate information in product labeling. Trials in children must be supported by appropriate toxicology and formulation work, which tends to delay completion of work in children until after the drug is available for adults. The Pediatric Research Equity Act (PREA) contains a decision tree to help companies devise an appropriate pediatric program for drugs in development. The medical community does not currently endorse the assumption that the progression of epilepsy and response to treatment is the same in adults and children. Therefore, a complete drug development program in children is necessary and includes efficacy and safety trials along with pharmacokinetic studies. These studies are needed to justify the risk/benefit in children. Formulations appropriate for children are needed. Seizure diaries must be maintained by caretakers and in the case of infants, seizures may need to be counted by EEG. Early planning and discussion of a pediatric program with regulatory agencies will facilitate this work.

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

    PubMed

    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

  12. Inverse Association between Sodium Channel-Blocking Antiepileptic Drug Use and Cancer: Data Mining of Spontaneous Reporting and Claims Databases

    PubMed Central

    Takada, Mitsutaka; Fujimoto, Mai; Motomura, Haruka; Hosomi, Kouichi

    2016-01-01

    Purpose: Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. Recently, a decreased risk of cancer associated with sodium channel-blocking antiepileptic drugs (AEDs) has become a research focus of interest. The purpose of this study was to test the hypothesis that the use of sodium channel-blocking AEDs are inversely associated with cancer, using different methodologies, algorithms, and databases. Methods: A total of 65,146,507 drug-reaction pairs from the first quarter of 2004 through the end of 2013 were downloaded from the US Food and Drug Administration Adverse Event Reporting System. The reporting odds ratio (ROR) and information component (IC) were used to detect an inverse association between AEDs and cancer. Upper limits of the 95% confidence interval (CI) of < 1 and < 0 for the ROR and IC, respectively, signified inverse associations. Furthermore, using a claims database, which contains 3 million insured persons, an event sequence symmetry analysis (ESSA) was performed to identify an inverse association between AEDs and cancer over the period of January 2005 to May 2014. The upper limit of the 95% CI of adjusted sequence ratio (ASR) < 1 signified an inverse association. Results: In the FAERS database analyses, significant inverse associations were found between sodium channel-blocking AEDs and individual cancers. In the claims database analyses, sodium channel-blocking AED use was inversely associated with diagnoses of colorectal cancer, lung cancer, gastric cancer, and hematological malignancies, with ASRs of 0.72 (95% CI: 0.60 - 0.86), 0.65 (0.51 - 0.81), 0.80 (0.65 - 0.98), and 0.50 (0.37 - 0.66), respectively. Positive associations between sodium channel-blocking AEDs and cancer were not found in the study. Conclusion: Multi-methodological approaches using different methodologies, algorithms, and databases suggest that sodium channel-blocking AED use is inversely associated with colorectal cancer, lung cancer, gastric

  13. A Clinical Evaluation of Gingival Overgrowth in Children on Antiepileptic Drug Therapy

    PubMed Central

    Chopra, Saroj; Thomas, Abi M; Pandian, Jeyraj

    2016-01-01

    Introduction Gingival overgrowth, a well-known side effect of chronic phenytoin therapy has also been known to be caused by other anti epileptic drugs (AED’s). Various factors like plaque, gingival inflammation, and periodontal health have been postulated to effect gingival overgrowth. Aim To identify the AED having an effect on gingival overgrowth and to study the factors affecting it. Materials and Methods Three groups of 30 children each on monotherapy of phenytoin, sodium valproate, and carbamazepine were longitudinally followed for six months. Their oral and epileptic health status was assessed and were monitored for change in plaque levels, gingival inflammation, probing depth and the status of gingival overgrowth at baseline, at the end of 3 months and finally at the end of 6 months. The data was recorded and statistically analysed. Results Phenytoin caused gingival overgrowth in a significant number of children (53.6%) within 3 months. Sodium valproate also led to gingival overgrowth, but not upto statistically significant levels. Patients on carbamazepine did not show any signs of gingival overgrowth. Gingival overgrowth is seen more on buccal side, in the anterior segment and in the lower arch. No correlation could be found between, either plaque level, or gingival inflammation with gingival overgrowth. Probing depth could be positively correlated with gingival overgrowth. Conclusion Phenytoin is the drug, which can be chiefly implicated for causing gingival overgrowth. Sodium valproate carries the potential for gingival overgrowth, although only up to clinically insignificant levels in 6 months. Carbamazepine can be considered a safe drug in children in relation to gingival overgrowth. PMID:26894172

  14. The effect of imepitoin, a recently developed antiepileptic drug, on thyroid parameters and fat metabolism in healthy Beagle dogs.

    PubMed

    Bossens, K; Daminet, S; Duchateau, L; Rick, M; Van Ham, L; Bhatti, S

    2016-07-01

    Since early 2013, imepitoin has been used in most European countries for the management of recurrent single generalised epileptic seizures in dogs with idiopathic epilepsy. It has been reported that imepitoin is as effective as phenobarbital (PB) in controlling seizures in dogs with newly diagnosed idiopathic epilepsy and it has a clinically superior safety profile. As the use of imepitoin gains popularity, its effect on serum thyroid parameters warrants further investigation since long-term PB administration influences thyroid parameters in dogs, which could lead to misinterpretation of laboratory results and incorrect diagnosis of thyroidal illness. A prospective study was conducted to compare the effect of orally administered PB and imepitoin on serum concentrations of total thyroxine (TT4), triiodothyronine, free thyroxine, thyroglobulin autoantibodies, thyroid-stimulating hormone, cholesterol and triglycerides in healthy Beagle dogs. These parameters were determined prior to and at 6, 12 and 18 weeks after antiepileptic drug administration. The starting dose of PB (5 mg/kg PO twice daily; range, 4.4-6.0 mg/kg) was monitored and adjusted to obtain optimal therapeutic serum concentrations (30-35 g/mL). Imepitoin was administered at 30 mg/kg PO twice daily (range, 29.2-35.7 mg/kg). Imepitoin administration did not affect any of the thyroid parameters over an 18-week period. In contrast, serum TT4 concentrations decreased significantly over time in dogs receiving PB (P <0.05). Serum cholesterol concentrations increased significantly over time in dogs in the imepitoin group, but not to the same extent as commonly seen in dogs with primary hypothyroidism.

  15. The effect of imepitoin, a recently developed antiepileptic drug, on thyroid parameters and fat metabolism in healthy Beagle dogs.

    PubMed

    Bossens, K; Daminet, S; Duchateau, L; Rick, M; Van Ham, L; Bhatti, S

    2016-07-01

    Since early 2013, imepitoin has been used in most European countries for the management of recurrent single generalised epileptic seizures in dogs with idiopathic epilepsy. It has been reported that imepitoin is as effective as phenobarbital (PB) in controlling seizures in dogs with newly diagnosed idiopathic epilepsy and it has a clinically superior safety profile. As the use of imepitoin gains popularity, its effect on serum thyroid parameters warrants further investigation since long-term PB administration influences thyroid parameters in dogs, which could lead to misinterpretation of laboratory results and incorrect diagnosis of thyroidal illness. A prospective study was conducted to compare the effect of orally administered PB and imepitoin on serum concentrations of total thyroxine (TT4), triiodothyronine, free thyroxine, thyroglobulin autoantibodies, thyroid-stimulating hormone, cholesterol and triglycerides in healthy Beagle dogs. These parameters were determined prior to and at 6, 12 and 18 weeks after antiepileptic drug administration. The starting dose of PB (5 mg/kg PO twice daily; range, 4.4-6.0 mg/kg) was monitored and adjusted to obtain optimal therapeutic serum concentrations (30-35 g/mL). Imepitoin was administered at 30 mg/kg PO twice daily (range, 29.2-35.7 mg/kg). Imepitoin administration did not affect any of the thyroid parameters over an 18-week period. In contrast, serum TT4 concentrations decreased significantly over time in dogs receiving PB (P <0.05). Serum cholesterol concentrations increased significantly over time in dogs in the imepitoin group, but not to the same extent as commonly seen in dogs with primary hypothyroidism. PMID:27240915

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

    PubMed

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

  17. Improvement of physicochemical properties of an antiepileptic drug by salt engineering.

    PubMed

    Rahman, Ziyaur; Zidan, Ahmed S; Samy, Raghu; Sayeed, Vilayat A; Khan, Mansoor A

    2012-09-01

    The focus of the present investigation was to evaluate the feasibility of using cyclamic salt of lamotrigine in order to improve its solubility and intrinsic dissolution rate (IDR). The salt was prepared by solution crystallization method and characterized chemically by fourier transform infrared spectroscopy (FTIR), proton ((1)H) and carbon ((13)C) nuclear magnetic resonance (liquid and solid, NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), physicochemically for solubility, IDR, solution and solid-state stability, and polymorphism by solution recrystallization and slurry conversion studies. The FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt formation. The salt formation increased lamotrigine solubility by 19-fold and IDR by 4.9-fold in water. The solution and solid-state stability were similar to parent molecule and were resistant to polymorphic transformation. In conclusion, cyclamic salt of lamotrigine provides another potential avenue for the pharmaceutical development of lamotrigine with improved physicochemical properties especially for pediatric population. It is also possible that appropriate dosage forms can be formulated with much lower drug amount and better safety profile than existing products. PMID:22588676

  18. Antiepileptic drugs (AEDs) polypharmacy could lead to buried pharmacokinetic interactions due to CYP450.

    PubMed

    Tolou-Ghamari, Z

    2012-09-01

    CYP450 enzymes are basics for the metabolism of several medications such as numerous AEDs. As AEDs polypharmacy could lead to hidden pharmacokinetic interactions due to CYP450, there fore, the aim of this study was to determine a proper guide line for AEDs prescription in Iranian epileptic population. A cross-sectional study of fifty-four patients' (n=23 females; n= 31 males with a mean age of 27 years) located in the Epilepsy Ward of Kashani Hospital of Isfahan University of Medical Sciences was carried out during the year 2011. Variables including sex, age, age of seizureonset, type and number of AEDs were recorded in d-Base. Results showed that the number of prescriptions based on AEDs polypharmacy was 77.8%. The most important drugs in prescriptions were carbamazepine (n=41) that is a potent inducer of CYP450 and valproic acid (n=31) that is a potent inhibitor of CYP450 simultaneously. Administration of AEDs was based on: three (n=17), four (n=7), five (n=4) or six (n=3) AEDs simultaneously. To avoid side effects, in prescribing AEDs that act as CYP450 inhibitors or inducers concomitantly, their spectrum of interactions should be predicted.

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

    PubMed

    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

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

    PubMed Central

    Xu, Xin; Fang, Weidong; Zeng, Kebin; Yang, Mingming; Li, Chenyu; Wang, Shasha; Li, Minghui; Wang, Xuefeng

    2015-01-01

    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 negative

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

    PubMed

    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

  2. Antiepileptic drugs and the risk of ischaemic stroke and myocardial infarction: a population-based cohort study

    PubMed Central

    Renoux, Christel; Dell'Aniello, Sophie; Saarela, Olli; Filion, Kristian B; Boivin, Jean-François

    2015-01-01

    Objectives Hepatic enzyme-inducing antiepileptic drugs (AEDs) increase serum lipid levels and other atherogenic markers via the induction of cytochrome P450 and may therefore increase the risk of vascular events. We sought to assess the risk of ischaemic stroke and myocardial infarction (MI) according to AED enzymatic properties. Design Population-based cohort study with nested case–control analysis. Setting 650 general practices in the UK contributing to the Clinical Practice Research Datalink. Participants A cohort of 252 407 incident AED users aged 18 or older between January 1990 and April 2013. For each case of ischaemic stroke or MI, up to 10 controls were randomly selected among the cohort members in the risk sets defined by the case and matched on age, sex, indication for AED, calendar time and duration of follow-up. Interventions Current use of enzyme-inducing and enzyme-inhibiting AEDs compared with non-inducing AEDs. Primary outcome measures Incidence rate ratios (RRs) of ischaemic stroke and MI. Results 5069 strokes and 3636 MIs were identified during follow-up. Inducing AEDs use was associated with a small increased risk of ischaemic stroke (RR=1.16, 95% CI 1.02 to 1.33) relative to non-inducing AEDs, most likely due to residual confounding. However, current use of inducing AEDs for ≥24 months was associated with a 46% increased risk of MI (RR=1.46, 95% CI 1.15 to 1.85) compared with the same duration of non-inducing AED, corresponding to a risk difference of 1.39/1000 (95% CI 0.33 to 2.45) persons per year. Current use of inhibiting AED was associated with a decreased risk of MI (RR=0.81, 95% CI 0.66 to 1.00). Conclusions The use of enzyme-inducing AEDs was not associated with an increased risk of ischaemic stroke; a small increase of MI with prolonged use was observed. In contrast, use of inhibiting AEDs was associated with a decreased risk of MI. PMID:26270948

  3. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.

    PubMed

    Glauser, Tracy; Ben-Menachem, Elinor; Bourgeois, Blaise; Cnaan, Avital; Guerreiro, Carlos; Kälviäinen, Reetta; Mattson, Richard; French, Jacqueline A; Perucca, Emilio; Tomson, Torbjorn

    2013-03-01

    The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence

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

    PubMed

    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

    SciTech Connect

    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) medicine

  6. Treatment of cardiac arrhythmias in a mouse model of Rett syndrome with Na+-channel-blocking antiepileptic drugs.

    PubMed

    Herrera, José A; Ward, Christopher S; Pitcher, Meagan R; Percy, Alan K; Skinner, Steven; Kaufmann, Walter E; Glaze, Daniel G; Wehrens, Xander H T; Neul, Jeffrey L

    2015-04-01

    One quarter of deaths associated with Rett syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. The standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, does not prevent lethal arrhythmias. In contrast, acute treatment with the Na(+) channel blocker phenytoin prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of Na(+) channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after Na(+) channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on Na(+) channel blocker antiepileptic therapies. Thus, Na(+) channel blockers should be considered for the clinical management of LQT in individuals with RTT.

  7. N-alkylprotoporphyrin formation and hepatic porphyria in dogs after administration of a new antiepileptic drug candidate: mechanism and species specificity.

    PubMed

    Nicolas, Jean-Marie; Chanteux, Hugues; Mancel, Valérie; Dubin, Guy-Marie; Gerin, Brigitte; Staelens, Ludovicus; Depelchin, Olympe; Kervyn, Sophie

    2014-10-01

    A new antiepileptic synaptic vesicle 2a (SV2a) ligand drug candidate was tested in 4-week oral toxicity studies in rat and dog. Brown pigment inclusions were found in the liver of high-dose dogs. The morphology of the deposits and the accompanying liver changes (increased plasma liver enzymes, increased total hepatic porphyrin level, decreased liver ferrochelatase activity, combined induction, and inactivation of cytochrome P-450 CYP2B11) suggested disruption of the heme biosynthetic cascade. None of these changes was seen in rat although this species was exposed to higher parent drug levels. Toxicokinetic analysis and in vitro metabolism assays in hepatocytes showed that dog is more prone to oxidize the drug candidate than rat. Mass spectrometry analysis of liver samples from treated dogs revealed an N-alkylprotoporphyrin adduct. The elucidation of its chemical structure suggested that the drug transforms into a reactive metabolite which is structurally related to a known reference porphyrogenic agent allylisopropylacetamide. That particular metabolite, primarily produced in dog but neither in rat nor in human, has the potential to alkylate the prosthetic heme of CYP. Overall, the data suggested that the drug candidate should not be porphyrogenic in human. This case study further exemplifies the species variability in the susceptibility to drug-induced porphyria.

  8. Targeting γ-aminobutyric acid (GABA) carriers to the brain: potential relevance as antiepileptic pro-drugs.

    PubMed

    Semreen, Mohammad H; El-Shorbagi, Abdel-Nasser; Al-Tel, Taleb H; Alsalahat, Izzeddin M M

    2010-05-01

    The search for antiepileptic compounds with more selective activity continues to be an area of intensive investigation in medicinal chemistry. 3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives, 3a-g, potential prodrugs incorporating the neurotransmitter GABA were synthesized and studied for crossing the blood-brain barrier (BBB). Compounds were prepared from primary amines and carbon disulfide to give dithiocarbamates 2a-g which upon reaction in situ with formaldehyde provided the intermediates Ia-g. Addition of Ia-g onto GABA furnished the title compounds 3a-g. The structures were verified by spectral data and the amounts of the compounds in the brain were investigated by using HPLC. The concentration profiles of the tested compounds in mice brain were determined and the in vivo anticonvulsant activity was measured. PMID:20632978

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

    PubMed

    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.

  10. Abortion and compelled physician speech.

    PubMed

    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

  11. Abortion and compelled physician speech.

    PubMed

    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.

  12. Teratogenicity of Antiepileptic Medications

    PubMed Central

    Kluger, Benzi M.; Meador, Kimford J.

    2009-01-01

    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, and developmental disorders seen in childhood. However, the differential effects of individual AEDs remain uncertain. Data are accumulating which strongly suggest that these risks are highest in patients receiving polypharmacy and valproate. There is also modest evidence to suggest an increased risk for phenobarbital. While other older AEDs appear to carry some teratogenic risk, there is not adequate evidence to further stratify their risk. Clinical and basic science research regarding newer AEDs suggests equivalent, if not safer, profiles compared with older AEDs, but these data are inconclusive. Management of women with epilepsy should include a discussion of these risks, prophylactic treatment with folic acid, and the minimal use of polypharmacy and valproate needed to maintain optimum seizure control. PMID:18777479

  13. 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.

    PubMed

    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

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

    PubMed Central

    Hamer, Hajo; Schönherr, Jeremias; Petersein, Charlotte; Munzer, Alexander; Kirkby, Kenneth Clifford; Bauer, Katrin; Sack, Ulrich

    2014-01-01

    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. PMID:24757498

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

    PubMed

    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.

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

    PubMed

    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

  17. Suppression of inter-ictal spikes by CM40907. A double-blind placebo-controlled investigation and review of spike counting as a methodology for assessing the antiepileptic effect of drugs.

    PubMed

    Yepez-Lasso, R; Duncan, J S; Shorvon, S D

    1990-04-01

    To assess the efficacy of CM40907--a new antiepileptic drug--in suppressing inter-ictal spikes, 6 patients with severe intractable epilepsy and frequent spikes in their inter-ictal EEGs were entered in a double-blind placebo-controlled trial. The results show that CM40907 is efficacious in reducing spike counts in the first hour after oral administration. The results of the study are presented and inter-ictal spike counting as a method is discussed.

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

    PubMed

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

    2013-11-15

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

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Comparative safety of anti-epileptic drugs among infants and children exposed in utero or during breastfeeding: protocol for a systematic review and network meta-analysis

    PubMed Central

    2014-01-01

    Background Epilepsy affects about 1% of the general population. Anti-epileptic drugs (AEDs) prevent or terminate seizures in individuals with epilepsy. Pregnant women with epilepsy may continue taking AEDs. Many of these agents cross the placenta and increase the risk of major congenital malformations, early cognitive and developmental delays, and infant mortality. We aim to evaluate the comparative safety of AEDs approved for chronic use in Canada when administered to pregnant and breastfeeding women and the effects on their infants and children through a systematic review and network meta-analysis. Methods Studies examining the effects of AEDs administered to pregnant and breastfeeding women regardless of indication (e.g., epilepsy, migraine, pain, psychiatric disorders) on their infants and children will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case-control studies. The main literature search will be executed in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We will seek unpublished literature through searches of trial protocol registries and conference abstracts. The literature search results screening, data abstraction, and risk of bias appraisal will be performed by two individuals, independently. Conflicts will be resolved through discussion. The risk of bias of experimental and quasi-experimental studies will be appraised using the Cochrane Effective Practice and Organization of Care Risk-of-Bias tool, methodological quality of observational studies will be appraised using the Newcastle-Ottawa Scale, and quality of reporting of safety outcomes will be conducted using the McMaster Quality Assessment Scale of Harms (McHarm) tool. If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes that fulfill network meta-analysis assumptions. The primary

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

    PubMed

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

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. PMID:26711223

  2. Prescribing pattern of anti-epileptic drugs in an Italian setting of elderly outpatients: a population-based study during 2004–07

    PubMed Central

    Oteri, Alessandro; Trifirò, Gianluca; Gagliostro, Maria Silvia; Tari, Daniele Ugo; Moretti, Salvatore; Bramanti, Placido; Spina, Edoardo; Caputi, Achille Patrizio; Arcoraci, Vincenzo

    2010-01-01

    AIMS The aims of the study were to assess the trend of older and newer anti-epileptic drugs (AEDs) in the elderly population and to analyze the effects of a health-policy intervention with regard to AED use in general practice in a setting in Southern Italy. METHODS Data were extracted from the ‘Caserta-1’ Local-Health-Unit Arianna database in the years 2004–07. Patients aged over 65 years, receiving at least one AED prescription and registered in the lists of 88 general practitioners, were selected. The use of older and newer AEDs was calculated as 1 year prevalence and incidence of use and defined daily dose (DDD) per 1000 inhabitants day−1. Sub-analyses by gender, age and indication of use were performed. RESULTS Most of AED users were treated because of neuropathic pain (64.8%). However, the main indication of use for older AEDs (57.8%) was epilepsy, whereas newer AEDs (79.5%) were used for neuropathic pain. Prevalence and incidence of newer AED use increased until 2006, followed by a reduction in 2007. Newer AEDs, particularly gabapentin and pregabalin, were used in the treatment of more patients than older AEDs. However phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. CONCLUSIONS An increasing use of AEDs has been observed during 2004–07, mostly due to the prescription of newer compounds for neuropathic pain. The fall in the use of newer AEDs during 2007 coincides with revised re-imbursement criteria for gabapentin and pregabalin. The large use of phenobarbital in the elderly should be considered in the light of a risk of adverse drug reactions. PMID:20840443

  3. The Antiepileptic Drug Levetiracetam Suppresses Non-Convulsive Seizure Activity and Reduces Ischemic Brain Damage in Rats Subjected to Permanent Middle Cerebral Artery Occlusion

    PubMed Central

    Cuomo, Ornella; Rispoli, Vincenzo; Leo, Antonio; Politi, Giovanni Bosco; Vinciguerra, Antonio; di Renzo, Gianfranco; Cataldi, Mauro

    2013-01-01

    The antiepileptic drug Levetiracetam (Lev) has neuroprotective properties in experimental stroke, cerebral hemorrhage and neurotrauma. In these conditions, non-convulsive seizures (NCSs) propagate from the core of the focal lesion into perilesional tissue, enlarging the damaged area and promoting epileptogenesis. Here, we explore whether Lev neuroprotective effect is accompanied by changes in NCS generation or propagation. In particular, we performed continuous EEG recordings before and after the permanent occlusion of the middle cerebral artery (pMCAO) in rats that received Lev (100 mg/kg) or its vehicle immediately before surgery. Both in Lev-treated and in control rats, EEG activity was suppressed after pMCAO. In control but not in Lev-treated rats, EEG activity reappeared approximately 30-45 min after pMCAO. It initially consisted in single spikes and, then, evolved into spike-and-wave and polyspike-and-wave discharges. In Lev-treated rats, only rare spike events were observed and the EEG power was significantly smaller than in controls. Approximately 24 hours after pMCAO, EEG activity increased in Lev-treated rats because of the appearance of polyspike events whose power was, however, significantly smaller than in controls. In rats sacrificed 24 hours after pMCAO, the ischemic lesion was approximately 50% smaller in Lev-treated than in control rats. A similar neuroprotection was observed in rats sacrificed 72 hours after pMCAO. In conclusion, in rats subjected to pMCAO, a single Lev injection suppresses NCS occurrence for at least 24 hours. This electrophysiological effect could explain the long lasting reduction of ischemic brain damage caused by this drug. PMID:24236205

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

    PubMed

    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.

  5. [Objectives and practical aspects of antiepileptic medication].

    PubMed

    Auvin, Stéphane

    2015-01-01

    Antiepileptics are a group of drugs with various pharmacological properties and mechanisms of action. They are grouped together due to the fact that they are used to treat epilepsy. There are around twenty molecules in this group. Particular care needs to be taken when prescribing them for children as they carry risks.

  6. A Compelling Desire for Deafness

    ERIC Educational Resources Information Center

    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…

  7. Antiepileptic carbamazepine drug treatment induces alteration of membrane in red blood cells: possible positive effects on metabolism and oxidative stress.

    PubMed

    Ficarra, Silvana; Misiti, Francesco; Russo, Annamaria; Carelli-Alinovi, Cristiana; Bellocco, Ersilia; Barreca, Davide; Laganà, Giuseppina; Leuzzi, Ugo; Toscano, Giovanni; Giardina, Bruno; Galtieri, Antonio; Tellone, Ester

    2013-04-01

    Carbamazepine (CBZ) is an iminostilbene derivative commonly used for treatment of neuralgic pain and bipolar affective disorders. CBZ blood levels of treated patients are within the range of micromolar concentrations and therefore, significant interactions of this drug with erythrocytes are very likely. Moreover, the lipid domains of the cell membrane are believed to be one of the sites where iminostilbene derivatives exert their effects. The present study aimed to deeply characterize CBZ effects on erythrocytes, in order to identify extra and/or cytosolic cell targets. Our results indicate that erythrocyte morphological changes promoted by the drug, may be triggered by an alteration in band 3 functionality i.e. at the level of anionic flux. In addition, from a metabolic point of view this perturbation could be considered, at least in part, as a beneficial event because it could favour the CO2 elimination. Since lipid peroxidation, superoxide and free radical scavenging activities, caspase 3 activity and hemoglobin (Hb) functionality were not modified within the CBZ treated red blood cell (RBC), band 3 protein (B3) may well be a specific membrane target for CBZ and responsible for CBZ-induced toxic effects in erythrocytes. However some beneficial effects of this drug have been evidenced; among them an increased release of ATP and nitric oxide (NO) derived metabolites from erythrocytes to lumen, leading to an increased NO pool in the vasculature. In conclusion, these results indicate that CBZ, though considered responsible for toxic effects on erythrocytes, can also exhibit effects that at least in some conditions may be seen as beneficial.

  8. Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy.

    PubMed

    Vurucu, Sebahattin; Demirkaya, Erkan; Kul, Mustafa; Unay, Bulent; Gul, Davut; Akin, Ridvan; Gokçay, Erdal

    2008-04-01

    Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA. PMID:18234410

  9. Evaluation of cytochrome P450 inductions by anti-epileptic drug oxcarbazepine, 10-hydroxyoxcarbazepine, and carbamazepine using human hepatocytes and HepaRG cells.

    PubMed

    Sugiyama, Ikuo; Murayama, Norie; Kuroki, Ayaka; Kota, Jagannath; Iwano, Shunsuke; Yamazaki, Hiroshi; Hirota, Takashi

    2016-09-01

    Anti-epileptic drug oxcarbazepine is structurally related to carbamazepine, but has reportedly different metabolic pathway. Auto-induction potentials of oxcarbazepine, its pharmacologically active metabolite 10-hydroxyoxcarbazepine and carbamazepine were evaluated by cytochrome P450 (CYP) 1A2, CYP2B6 and CYP3A4 mRNA levels and primary metabolic rates using human hepatocytes and HepaRG cells. For the CYP1A2 the induction potential determined as the fold change in mRNA levels was 7.2 (range: 2.3-11.5) and 10.0 (6.2-13.7) for oxcarbazepine and carbamazepine, respectively, while 10-hydroxyoxcarbazepine did not induce. The fold change in mRNA levels for CYP2B6 was 11.5 (3.2-19.3), 7.0 (2.5-10.8) and 14.8 (3.1-29.1) for oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine, respectively. The fold change for CYP3A4 induction level by oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine was 3.5 (1.2-7.4), 2.7 (0.8-5.7) and 8.3 (3.5-14.5), respectively. The data suggest lower induction potential of oxcarbazepine and 10-hydroxyoxcarbazepine relative to carbamazepine. The results in HepaRG cells showed similar trend as the human hepatocytes. After incubation for 72 h in hepatocytes and HepaRG cells, auto-induction was evident for only carbamazepine metabolism. The 10-keto group instead of double bond at C10 position is evidently a determinant factor for limited auto-induction of P450 enzymes by oxcarbazepine. PMID:26711482

  10. The antiepileptic drug mephobarbital is not transported by P-glycoprotein or multidrug resistance protein 1 at the blood-brain barrier: a positron emission tomography study

    PubMed Central

    Mairinger, Severin; Bankstahl, Jens P.; Kuntner, Claudia; Römermann, Kerstin; Bankstahl, Marion; Wanek, Thomas; Stanek, Johann; Löscher, Wolfgang; Müller, Markus; Erker, Thomas; Langer, Oliver

    2013-01-01

    Summary Aim of this study was to determine whether the carbon-11-labelled antiepileptic drug [11C]mephobarbital is a substrate of P-glycoprotein (Pgp) and can be used to assess Pgp function at the blood-brain barrier (BBB) with positron emission tomography (PET). We performed paired PET scans in rats, wild-type (FVB) and Mdr1a/b(−/−) mice, before and after intravenous administration of the Pgp inhibitor tariquidar (15 mg/kg). Brain-to-blood AUC0-60 ratios in rats and brain AUC0-60 values of [11C]mephobarbital in wild-type and Mdr1a/b(−/−) mice were similar in scan 1 and scan 2, respectively, suggesting that in vivo brain distribution of [11C]mephobarbital is not influenced by Pgp efflux. Absence of Pgp transport was confirmed in vitro by performing concentration equilibrium transport assay in cell lines transfected with MDR1 or Mdr1a. PET experiments in wild-type mice, with and without pretreatment with the multidrug resistance protein (MRP) inhibitor MK571 (20 mg/kg), and in Mrp1(−/−) mice suggested that [11C]mephobarbital is also not transported by MRPs at the murine BBB, which was also supported by in vitro transport experiments using human MRP1-transfected cells. Our results are surprising as phenobarbital, the N-desmethyl derivative of mephobarbital, has been shown to be a substrate of Pgp, which suggests that N-methylation abolishes Pgp affinity of barbiturates. PMID:22342565

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

    PubMed Central

    Rocha, Luisa

    2008-01-01

    Experiments using male CD1 mice were carried out to investigate the effects of subchronic (daily administration for 8 days) pretreatments with drugs enhancing GABAergic transmission (diazepam, 10 mg/kg, ip; gabapentin, 100 mg/kg, po; or vigabatrin, 500 mg/kg, po) on pentylenetetrazol (PTZ)-induced seizures, 24 h after the last injection. Subchronic administration of diazepam reduced latencies to clonus, tonic extension and death induced by PTZ. Subchronic vigabatrin produced enhanced latency to the first clonus but faster occurrence of tonic extension and death induced by PTZ. Subchronic gabapentin did not modify PTZ-induced seizures. Autoradiography experiments revealed reduced benzodiazepine receptor binding in several brain areas after subchronic treatment with diazepam or gabapentin, whereas subchronic vigabatrin did not induce significant receptor changes. The present results indicate differential effects induced by the subchronic administration of diazepam, vigabatrin, and gabapentin on the susceptibility to PTZ-induced seizures, benzodiazepine receptor binding, or both. PMID:18830436

  12. Quantification of new antiepileptic drugs by liquid chromatography/electrospray ionization tandem mass spectrometry and its application to cellular uptake experiment using human placental choriocarcinoma BeWo cells.

    PubMed

    Furugen, Ayako; Kobayashi, Masaki; Nishimura, Ayako; Takamura, Shigeo; Narumi, Katsuya; Yamada, Takehiro; Iseki, Ken

    2015-10-01

    A method for quantification of new antiepileptic drugs, including lamotrigine (LTG), levetiracetam (LEV), gabapentin (GBP), and topiramate (TPM), in cellular samples, using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to better understand the membrane transport mechanisms of these drugs. Cell lysate was deproteinized by methanol containing LEV-d3 as an internal standard (IS). Chromatographic separation was performed on a C18 column using gradient elution with methanol-water-formic acid (10:90:0.1, v/v/v) and methanol-formic acid (100:0.1, v/v). Analytes were detected in positive ion electrospray mode with selected reaction monitoring (SRM). This method was applicable for a linear range of 5 to 500pmol for LTG; 5 to 1000pmol for LEV; 10 to 10,000pmol for GBP; and 5 to 5000pmol for TPM. The intra-day precision, inter-day precision, and accuracy data were assessed and found to be acceptable. This developed and validated method was then successfully applied to the investigation of uptake of the new antiepileptic drugs in placental choriocarcinoma BeWo cells. The intracellular concentration of these drugs in BeWo cells, accumulating over 30min at 37°C was in the order of GBP>LTG>LEV≈TPM. Furthermore, the uptake of GBP at 4°C was much lower than that at 37°C. The uptake of GBP was saturated at high concentrations. The kinetic parameters calculated for GBP uptake in BeWo cells were determined as Km of 105.4±6.4μM and Vmax at 8153±348pmol/mg protein/min. The novel method described here should enable investigators to elucidate the transport mechanisms of these antiepileptic drugs in BeWo cells.

  13. 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.

    PubMed

    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.

  14. Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs.

    PubMed

    Di Rosa, Gabriella; Lenzo, Patrizia; Parisi, Eleonora; Neri, Milena; Guerrera, Silvia; Nicotera, Antonio; Alibrandi, Angela; Germanò, Eva; Caccamo, Daniela; Spanò, Maria; Tortorella, Gaetano

    2013-12-01

    Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs. The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of "unknown cause" (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13μM/L (tHcy<9μM/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C. Plasma tHcy levels were not significantly related to the IQ scores

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

    PubMed Central

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

    2015-01-01

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

  16. The compelling anomaly of chemical intolerance.

    PubMed

    Miller, C S

    2001-03-01

    In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.

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

    ERIC Educational Resources Information Center

    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…

  18. Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and standard radiation and temozolomide.

    PubMed

    Gerstner, Elizabeth R; Eichler, April F; Plotkin, Scott R; Drappatz, Jan; Doyle, Colin L; Xu, Lei; Duda, Dan G; Wen, Patrick Y; Jain, Rakesh K; Batchelor, Tracy T

    2011-06-01

    Targeting angiogenesis in glioblastoma (GBM) may improve patient outcome by normalizing tumor vasculature and improving delivery of chemotherapeutics and oxygen. Consequently, concomitant administration of small molecule inhibitors of the VEGF pathway will likely have a positive impact on chemoradiation treatment outcome. We conducted a Phase I study of vatalanib, a small molecule inhibitor of VEGFR, PDGFR, and c-kit in patients with newly diagnosed GBM receiving radiation, temozolomide, and an enzyme-inducing anti-epileptic drug in order to determine the MTD of vatalanib in this patient population. We incorporated circulating biomarker and SNP analyses and pharmacokinetic studies. Nineteen patients were enrolled and the MTD was not reached at the time of study termination. Vatalanib was well tolerated with only 2 DLTs (thrombocytopenia and elevated transaminases). Other grade 3/4 toxicities included leukopenia, lymphopenia, neutropenia, and hand-foot syndrome. There were no wound-healing complications. Of the 13 patients evaluable for a radiographic response, 2 had a partial response and 9 had stable disease. Vatalanib significantly increased PlGF and sVEGFR1 in plasma circulation and decreased sVEGFR2 and sTie2. Plasma collagen IV increased significantly by day 50 of treatment. Vatalanib was well tolerated and this study demonstrates the safety of oral small molecule inhibitors in newly diagnosed GBM patients. Blood biomarkers may be useful as pharmacodynamic markers of response to anti-angiogenic therapies. PMID:20821342

  19. 4 CFR 28.43 - Compelling discovery.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 4 Accounts 1 2012-01-01 2012-01-01 false Compelling discovery. 28.43 Section 28.43 Accounts GOVERNMENT ACCOUNTABILITY OFFICE GENERAL PROCEDURES GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL APPEALS BOARD; PROCEDURES APPLICABLE TO CLAIMS CONCERNING EMPLOYMENT PRACTICES AT THE GOVERNMENT ACCOUNTABILITY...

  20. 4 CFR 28.43 - Compelling discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Compelling discovery. 28.43 Section 28.43 Accounts GOVERNMENT ACCOUNTABILITY OFFICE GENERAL PROCEDURES GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL APPEALS BOARD; PROCEDURES APPLICABLE TO CLAIMS CONCERNING EMPLOYMENT PRACTICES AT THE GOVERNMENT ACCOUNTABILITY...

  1. 4 CFR 28.43 - Compelling discovery.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 4 Accounts 1 2011-01-01 2011-01-01 false Compelling discovery. 28.43 Section 28.43 Accounts GOVERNMENT ACCOUNTABILITY OFFICE GENERAL PROCEDURES GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL APPEALS BOARD; PROCEDURES APPLICABLE TO CLAIMS CONCERNING EMPLOYMENT PRACTICES AT THE GOVERNMENT ACCOUNTABILITY...

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

    ERIC Educational Resources Information Center

    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…

  3. Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005–2011

    PubMed Central

    Italiano, Domenico; Capuano, Annalisa; Alibrandi, Angela; Ferrara, Rosarita; Cannata, Angelo; Trifirò, Gianluca; Sultana, Janet; Ferrajolo, Carmen; Tari, Michele; Tari, Daniele Ugo; Perrotta, Margherita; Pagliaro, Claudia; Rafaniello, Concita; Spina, Edoardo; Arcoraci, Vincenzo

    2015-01-01

    Aims The aim of the study was to analyze the prescribing pattern of both newer and older AEDs. Methods A population of almost 150 000 individuals registered with 123 general practitioners was included in this study. Patients who received at least one AED prescription over 2005–2011 were identified. The 1 year prevalence and cumulative incidence of AED use, by drug class and individual drug, were calculated over the study period. Potential predictors of starting therapy with newer AEDs were also investigated. Results The prevalence of use per 1000 inhabitants of older AEDs increased from 10.7 (95% CI10.1, 11.2) in 2005 to 13.0 (95% CI12.4, 13.6) in 2011, while the incidence remained stable. Newer AED incidence decreased from 9.4 (95% CI 8.9, 9.9) in 2005 to 7.0 (95% CI 6.6, 7.5) in 2011, with a peak of 15.5 (95% CI 14.8, 16.1) in 2006. Phenobarbital and valproic acid were the most commonly prescribed AEDs as starting therapy for epilepsy. Gabapentin and pregabalin accounted for most new pain-related prescriptions, while valproic acid and lamotrigine were increasingly used for mood disorders. Female gender (OR 1.36, 95% CI 1.20, 1.53), age ranging between 45–54 years (OR 1.39, 95% CI 1.16, 1.66) and pain as an indication (OR 16.7, 95% CI, 13.1, 21.2) were associated with newer AEDs starting therapy. Conclusions Older AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin. PMID:25556909

  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

    PubMed Central

    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)

    PubMed Central

    Marimuthu, Priya; Varadarajan, Sathyanarayanan; Krishnan, Muthuraj; Shanmugam, Sundar; Kunjuraman, Gireesh; Ravinder, Jamuna Rani; Arumugam, Balasubramanian; Alex, Divya; Swaminathan, Porchelvan

    2016-01-01

    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 16th 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 16th 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. PMID:27570386

  6. Mechanistic and conformational studies on the interaction of a platinum(II) complex containing an antiepileptic drug, levetiracetam, with bovine serum albumin by optical spectroscopic techniques in aqueous solution.

    PubMed

    Shahabadi, Nahid; Hadidi, Saba

    2015-02-01

    Fluorescence spectroscopy in combination with circular dichroism (CD) and ultraviolet-visible (UV-vis) absorption spectroscopy were employed to investigate the binding of a new platinum(II) complex containing an antiepileptic drug "Levetiracetam" to bovine serum albumin (BSA) under the physiological conditions. In the mechanism discussion, it was proved that the fluorescence quenching of BSA by Pt(II) complex is a result of the formation of Pt(II) complex-BSA complex. The thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures (283, 298, and 310 K) were calculated, and the negative value for ΔH and ΔS indicate that the hydrogen bonds and van der Waals interactions play major roles in Pt(II) complex-BSA association. Binding studies concerning the number of binding sites (n~1) and apparent binding constant K b were performed by fluorescence quenching method. The site marker competitive experiments indicated that the binding of Pt(II) complex to BSA primarily took place in site II. Based on the Förster's theory, the average binding distance between Pt(II) complex and BSA was obtained (r = 5.29 nm). Furthermore, UV-vis, CD, and synchronous fluorescence spectrum were used to investigate the structural change of BSA molecules with addition of Pt(II) complex. These results indicate that the binding of Pt(II) complex to BSA causes apparent change in the secondary structure of BSA and do affect the microenvironment around the tryptophan residue.

  7. Mechanistic and conformational studies on the interaction of a platinum(II) complex containing an antiepileptic drug, levetiracetam, with bovine serum albumin by optical spectroscopic techniques in aqueous solution.

    PubMed

    Shahabadi, Nahid; Hadidi, Saba

    2015-02-01

    Fluorescence spectroscopy in combination with circular dichroism (CD) and ultraviolet-visible (UV-vis) absorption spectroscopy were employed to investigate the binding of a new platinum(II) complex containing an antiepileptic drug "Levetiracetam" to bovine serum albumin (BSA) under the physiological conditions. In the mechanism discussion, it was proved that the fluorescence quenching of BSA by Pt(II) complex is a result of the formation of Pt(II) complex-BSA complex. The thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures (283, 298, and 310 K) were calculated, and the negative value for ΔH and ΔS indicate that the hydrogen bonds and van der Waals interactions play major roles in Pt(II) complex-BSA association. Binding studies concerning the number of binding sites (n~1) and apparent binding constant K b were performed by fluorescence quenching method. The site marker competitive experiments indicated that the binding of Pt(II) complex to BSA primarily took place in site II. Based on the Förster's theory, the average binding distance between Pt(II) complex and BSA was obtained (r = 5.29 nm). Furthermore, UV-vis, CD, and synchronous fluorescence spectrum were used to investigate the structural change of BSA molecules with addition of Pt(II) complex. These results indicate that the binding of Pt(II) complex to BSA causes apparent change in the secondary structure of BSA and do affect the microenvironment around the tryptophan residue. PMID:25427597

  8. Antiepileptic Activity of Preferential Inhibitors of Persistent Sodium Current

    PubMed Central

    Anderson, Lyndsey L.; Thompson, Christopher H.; Hawkins, Nicole A.; Nath, Ravi D.; Petersohn, Adam A.; Rajamani, Sridharan; Bush, William S.; Frankel, Wayne N.; Vanoye, Carlos G.; Kearney, Jennifer A.; George, Alfred L.

    2014-01-01

    Objective Evidence from basic neurophysiology and molecular genetics has implicated persistent sodium current conducted by voltage-gated sodium (NaV) channels as a contributor to the pathogenesis of epilepsy. Many antiepileptic drugs target NaV channels and modulate neuronal excitability mainly by a use-dependent block of transient sodium current, although suppression of persistent current may also contribute to the efficacy of these drugs. We hypothesized that a drug or compound capable of preferential inhibition of persistent sodium current would have antiepileptic activity. Methods We examined the antiepileptic activity of two selective persistent sodium current blockers ranolazine, an FDA-approved drug for treatment of angina pectoris, and GS967, a novel compound with more potent effects on persistent current, in the epileptic Scn2aQ54 mouse model. We also examined the effect of GS967 in the maximal electroshock model and evaluated effects of the compound on neuronal excitability, propensity for hilar neuron loss, development of mossy fiber sprouting and survival of Scn2aQ54 mice. Results We found that ranolazine was capable of reducing seizure frequency by ~50% in Scn2aQ54 mice. The more potent persistent current blocker GS967 reduced seizure frequency by greater than 90% in Scn2aQ54 mice and protected against induced seizures in the maximal electroshock model. GS967 greatly attenuated abnormal spontaneous action potential firing in pyramidal neurons acutely isolated from Scn2aQ54 mice. In addition to seizure suppression in vivo, GS967 treatment greatly improved the survival of Scn2aQ54 mice, prevented hilar neuron loss, and suppressed the development of hippocampal mossy fiber sprouting. Significance Our findings indicate that the selective persistent sodium current blocker GS967 has potent antiepileptic activity and this compound could inform development of new agents. PMID:24862204

  9. New mixed ligand zinc(II) complexes based on the antiepileptic drug sodium valproate and bioactive nitrogen-donor ligands. Synthesis, structure and biological properties.

    PubMed

    Darawsheh, Mohanad; Abu Ali, Hijazi; Abuhijleh, A Latif; Rappocciolo, Emilia; Akkawi, Mutaz; Jaber, Suhair; Maloul, Salam; Hussein, Yasmeen

    2014-07-23

    Starting from the precursor [Zinc Valproate complex] (1), new mixed ligand zinc(II) complexes of valproic acid and nitrogen-based ligands, formulating as, [Zn(valp)22,9-dmphen] (2), [Zn2(valp)4(quin)2] (3), [Zn(valp)2(2-ampy)2] (4), and [Zn(valp)2(2-ampic)2] (5) (valp = valproate, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, quin = quinoline, 2-ampy = 2-aminopyridine, 2-ampic = 2-amino-6-picoline) were synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The crystal structures of complexes 2, 3 and 4 were determined using single-crystal X-ray diffraction. The complexes were also evaluated for their anti-bacterial activity using in-vitro agar diffusion method against three Gram-positive (Micrococcus luteus, Staphylococcus aureus, and Bacillus subtilis) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) species. Complex 2 showed considerable activity against all tested microorganisms and the effect of complexation on the anti-bacterial activity of the parent ligand of 2 was also investigated. The anti-bacterial activity of 2,9-dmphen against Gram-negative bacteria was enhanced upon complexation with zinc valproate. On the other hand, complexes 1 and 3 showed weak inhibition activity against the tested species and complexes 4 and 5 didn't show any activity at all. Two methods were used for testing the inhibition of ferriprotoporphyrinIX bio-mineralization: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment which considered being the target of many known anti-malarial drugs such as Chloroquine and Amodiaquine. Results showed that the efficiency of complex 2 in preventing the formation of β-Hematin was 80%. The efficiency of Amodiaquine as a standard drug was reported to give 91%.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  11. The Relationship among Side Effects Associated with Anti-Epileptic Medications in Those with Intellectual Disability

    ERIC Educational Resources Information Center

    Sipes, Megan; Matson, Johnny L.; Belva, Brian; Turygin, Nicole; Kozlowski, Alison M.; Horovitz, Max

    2011-01-01

    Seizures are fairly common in those with intellectual disabilities. In order to treat these seizures, antiepileptic drugs (AEDs) are often used and in many cases are effective. However, these medications often create a variety of associated side effects. In order to monitor these side effects, measures such as the SEIZES-B have been used. While…

  12. 37 CFR 41.156 - Compelling testimony and production.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... production. 41.156 Section 41.156 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK... Cases § 41.156 Compelling testimony and production. (a) Authorization required. A party seeking to compel testimony or production of documents or things must file a miscellaneous motion for...

  13. 16 CFR 1025.36 - Motions to compel discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Motions to compel discovery. 1025.36 Section 1025.36 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL RULES OF PRACTICE FOR ADJUDICATIVE PROCEEDINGS Discovery, Compulsory Process § 1025.36 Motions to compel discovery. If a party...

  14. 49 CFR 511.36 - Motions to compel discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 6 2011-10-01 2011-10-01 false Motions to compel discovery. 511.36 Section 511.36 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ADJUDICATIVE PROCEDURES Discovery; Compulsory Process § 511.36 Motions to compel discovery. If...

  15. Cultivating Diversity and Spirituality: A Compelling Interest for Institutional Priority

    ERIC Educational Resources Information Center

    Paredes-Collins, Kristin

    2013-01-01

    Historically, Christian colleges and universities have struggled to incorporate racial and ethnic diversity into White and homogenous campuses. Research indicates that a positive racial climate is essential to promote spiritual growth for students from diverse backgrounds. As a result, diversity is a compelling interest for Christian institutions.…

  16. 48 CFR 18.104 - Unusual and compelling urgency.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Unusual and compelling urgency. 18.104 Section 18.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities...

  17. 48 CFR 18.104 - Unusual and compelling urgency.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Unusual and compelling urgency. 18.104 Section 18.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities...

  18. 48 CFR 18.104 - Unusual and compelling urgency.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Unusual and compelling urgency. 18.104 Section 18.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities...

  19. 48 CFR 18.104 - Unusual and compelling urgency.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Unusual and compelling urgency. 18.104 Section 18.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities...

  20. 48 CFR 18.104 - Unusual and compelling urgency.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Unusual and compelling urgency. 18.104 Section 18.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES EMERGENCY ACQUISITIONS Available Acquisition Flexibilities...

  1. 49 CFR 511.36 - Motions to compel discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Motions to compel discovery. 511.36 Section 511.36 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ADJUDICATIVE PROCEDURES Discovery; Compulsory Process §...

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

    PubMed

    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.

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

    PubMed Central

    Xiang, Jun; Jiang, Yugang

    2013-01-01

    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. PMID:24317434

  4. Design and synthesis of chroman derivatives with dual anti-breast cancer and antiepileptic activities.

    PubMed

    Rawat, Pinki; Verma, Saurabh Manaswita

    2016-01-01

    A series of chroman derivatives was designed, prepared, and examined for their anti-breast cancer and antiepileptic activities. All synthesized compounds yielded results that were in good agreement with spectral data. The bioassay showed that some of the resultant compounds exerted remarkable inhibitory effects on growth of human breast cancer cell line MCF-7. In particular, compound 6i (the concentration required for 50% inhibition of cell growth [GI50] =34.7 µM) exerted promising anticancer activity toward MCF-7 cell line. Additionally, compounds 6b, 6c, 6d, 6e, 6g, 6i, and 6l showed advanced antiepileptic activity than reference drugs. None of the compounds showed neurotoxicity, as determined by the rotarod test. The obtained results proved that these distinctive compounds could be relevant as models for future discovery and research, as well as for the production of more number of active derivatives. PMID:27621598

  5. Design and synthesis of chroman derivatives with dual anti-breast cancer and antiepileptic activities

    PubMed Central

    Rawat, Pinki; Verma, Saurabh Manaswita

    2016-01-01

    A series of chroman derivatives was designed, prepared, and examined for their anti-breast cancer and antiepileptic activities. All synthesized compounds yielded results that were in good agreement with spectral data. The bioassay showed that some of the resultant compounds exerted remarkable inhibitory effects on growth of human breast cancer cell line MCF-7. In particular, compound 6i (the concentration required for 50% inhibition of cell growth [GI50] =34.7 µM) exerted promising anticancer activity toward MCF-7 cell line. Additionally, compounds 6b, 6c, 6d, 6e, 6g, 6i, and 6l showed advanced antiepileptic activity than reference drugs. None of the compounds showed neurotoxicity, as determined by the rotarod test. The obtained results proved that these distinctive compounds could be relevant as models for future discovery and research, as well as for the production of more number of active derivatives. PMID:27621598

  6. Design and synthesis of chroman derivatives with dual anti-breast cancer and antiepileptic activities

    PubMed Central

    Rawat, Pinki; Verma, Saurabh Manaswita

    2016-01-01

    A series of chroman derivatives was designed, prepared, and examined for their anti-breast cancer and antiepileptic activities. All synthesized compounds yielded results that were in good agreement with spectral data. The bioassay showed that some of the resultant compounds exerted remarkable inhibitory effects on growth of human breast cancer cell line MCF-7. In particular, compound 6i (the concentration required for 50% inhibition of cell growth [GI50] =34.7 µM) exerted promising anticancer activity toward MCF-7 cell line. Additionally, compounds 6b, 6c, 6d, 6e, 6g, 6i, and 6l showed advanced antiepileptic activity than reference drugs. None of the compounds showed neurotoxicity, as determined by the rotarod test. The obtained results proved that these distinctive compounds could be relevant as models for future discovery and research, as well as for the production of more number of active derivatives.

  7. The antiepileptic primidone impairs male rat sexual behavior.

    PubMed

    Westerman, Ashley T; Roma, Peter G; Creed, Evan T; Hurwitz, Zachary E; Dominguez, Juan M

    2009-08-01

    Many antiepileptic drugs (AEDs) produce sexual impairments. Of commonly prescribed AEDs, primidone produces the greatest impairments. Here we examined the effects of primidone on male rat sexual behavior. Sexually-experienced male rats received administration of either vehicle or primidone. After baseline measures were obtained, the effects of daily primidone treatment on home cage sexual performance were assessed three times over the course of 14 days. Motor activity and sucrose preference were also assessed during this time period. Results indicate that primidone impaired copulation but not sexual motivation. Specifically, animals receiving primidone displayed fewer ejaculations, required more time to achieve an intromission, and displayed fewer intromissions per attempted mount as evidenced by a lower intromission ratio. However, animals treated with primidone also chose a goal box containing a sexually-receptive female in an x-maze as often as animals receiving vehicle. The lower intromission ratio suggests an inability to achieve intromissions perhaps as a result of impaired erectile function. Primidone did not affect motor activity or sucrose consumption, an additional measure of natural reward. Together, these data indicate that primidone impairs male sexual activity and suggest that these impairments result primarily from changes in erectile function and not changes to mechanisms mediating motivation.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed

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

    2015-04-16

    Objetivo. Elaborar unas recomendaciones basadas en evidencias cientificas y en consenso de los autores y revisores, que aborden las cuestiones basicas acerca de la combinacion de farmacos antiepilepticos. Desarrollo. Un comite de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia (SAdE), constituido por siete neurologos, tres neuropediatras y un neurologo-neurofisiologo, todos con especial competencia en epilepsia, promovieron la realizacion de una revision bibliografica exhaustiva entre 55 expertos en epilepsia pertenecientes a la SAdE, en busca de evidencias disponibles relacionadas con temas diagnosticos o terapeuticos en epilepsia. La guia se estructuro en 35 capitulos. Uno de los capitulos abordo la combinacion de farmacos antiepilepticos en el tratamiento de la epilepsia. Basandose en 77 citas bibliograficas y en la opinion consensuada de autores y revisores, se confecciono una serie de recomendaciones de facil aplicacion. Conclusiones. La combinacion de farmacos antiepilepticos en los pacientes con epilepsia cuyas crisis no estan controladas con un solo farmaco puede conseguir en numerosas ocasiones que entren en remision. Existe una serie de factores relacionados con el tipo de epilepsia y caracteristicas del paciente y con los farmacos antiepilepticos que se van a utilizar en combinacion que pueden favorecer el exito terapeutico. Se debe evitar en lo posible el sobretratamiento con la combinacion de farmacos antiepilepticos. Los resultados de esta revision proveen unas recomendaciones sobre el tratamiento combinado con farmacos antiepilepticos, basadas en evidencias cientificas y en el consenso de los autores, utiles, sencillas y aplicables en los diferentes niveles asistenciales.

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

    ERIC Educational Resources Information Center

    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…

  12. In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds

    PubMed Central

    Mathew, Shilu; Faheem, Muhammad; Al-Malki, Abdulrahman L; Kumosani, Taha A; Qadri, Ishtiaq

    2015-01-01

    Epilepsy is a neurological disorder affecting more than 50 million people worldwide. It can be controlled by antiepileptic drugs (AEDs) but more than 30% patients are still resistant to AEDs. To overcome this problem, researchers are trying to develop novel approaches to treat epilepsy including the use of herbal medicines. The γ-amino butyric acid type-A receptor associated protein (GABARAP) is ubiquitin-like modifier implicated in the intracellular trafficking of GABAAR. An in silico mutation was created at 116 amino acid position G116A, and an in silico study was carried out to identify the potential binding inhibitors (with antiepileptic properties) against the active sites of GABARAP. Five different plant derived compounds namely (a) Aconitine (b) Berberine (c) Montanine (d) Raubasine (e) Safranal were selected, and their quantitative structure-activity relationships (QSAR) have been conducted to search the inhibitory activity of the selected compounds. The results have shown maximum number of hydrogen bond (H-bond) interactions of Raubasine with highest interaction energy among all of the five compounds. So, Raubasine could be the best fit ligand of GABARAP but in vitro, and in vivo studies are necessary for further confirmation. PMID:26124559

  13. 12 CFR 261.23 - Subpoenas, orders compelling production, and other process.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 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...

  14. 12 CFR 261.23 - Subpoenas, orders compelling production, and other process.

    Code of Federal Regulations, 2010 CFR

    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...

  15. An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes.

    PubMed

    Gerard, Elizabeth E; Meador, Kimford J

    2015-06-01

    Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age. In utero exposure to some AEDs can have significant cognitive and behavioral consequences for the unborn child. Recently, prospective studies of women taking AEDs during pregnancy have added significantly to our understanding of cognitive and behavioral teratogenic risks posed by fetal AED exposure. Valproate is clearly associated with impaired cognitive development as well as an increased risk of disorders such as autism and autism spectrum disorder. Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated with more favorable cognitive and behavioral outcomes than valproate, but more data are required to clarify if these AEDs have more subtle effects on cognition and behavior. There are insufficient data on the developmental effects of other AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are poorly understood, including the genetic factors that affect susceptibility to AEDs. PMID:27617120

  16. Antiepileptic medications in autism spectrum disorder: a systematic review and meta-analysis.

    PubMed

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

    2014-04-01

    Electroencephalogram-recorded epileptiform activity is common in children with autism spectrum disorder (ASD), even without clinical seizures. A systematic literature search identified 7 randomized, placebo-controlled trials of antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate, and one each of lamotrigine, levetiracetam, and topiramate. Meta-analysis revealed no significant difference between medication and placebo in four studies targeting irritability/agitation and three studies investigating global improvement, although limitations include lack of power and different medications with diverse actions. Across all seven studies, there was no significant difference in discontinuation rate between two groups. AEDs do not appear to have a large effect size to treat behavioral symptoms in ASD, but further research is needed, particularly in the subgroup of patients with epileptiform abnormalities. PMID:24077782

  17. An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes

    PubMed Central

    Gerard, Elizabeth E.; Meador, Kimford J.

    2015-01-01

    Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age. In utero exposure to some AEDs can have significant cognitive and behavioral consequences for the unborn child. Recently, prospective studies of women taking AEDs during pregnancy have added significantly to our understanding of cognitive and behavioral teratogenic risks posed by fetal AED exposure. Valproate is clearly associated with impaired cognitive development as well as an increased risk of disorders such as autism and autism spectrum disorder. Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated with more favorable cognitive and behavioral outcomes than valproate, but more data are required to clarify if these AEDs have more subtle effects on cognition and behavior. There are insufficient data on the developmental effects of other AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are poorly understood, including the genetic factors that affect susceptibility to AEDs. PMID:27617120

  18. An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes

    PubMed Central

    Gerard, Elizabeth E.; Meador, Kimford J.

    2015-01-01

    Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age. In utero exposure to some AEDs can have significant cognitive and behavioral consequences for the unborn child. Recently, prospective studies of women taking AEDs during pregnancy have added significantly to our understanding of cognitive and behavioral teratogenic risks posed by fetal AED exposure. Valproate is clearly associated with impaired cognitive development as well as an increased risk of disorders such as autism and autism spectrum disorder. Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated with more favorable cognitive and behavioral outcomes than valproate, but more data are required to clarify if these AEDs have more subtle effects on cognition and behavior. There are insufficient data on the developmental effects of other AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are poorly understood, including the genetic factors that affect susceptibility to AEDs.

  19. Clinically significant drug interactions.

    PubMed

    Ament, P W; Bertolino, J G; Liszewski, J L

    2000-03-15

    A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. 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. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references. PMID:10750880

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

    PubMed

    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.

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

    ERIC Educational Resources Information Center

    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…

  2. Epilepsy: new drug targets and neurostimulation.

    PubMed

    Asconapé, Jorge J

    2013-08-01

    Despite advances in the medical and surgical therapy for epilepsy, about 30% of patients do not achieve full seizure control. In the past 5 years new antiepileptic drugs have been approved for clinical use. Some of these drugs have unique, novel mechanisms of action. Overall efficacy of these agents, however, seems similar to other antiepileptic drugs. Vagus nerve stimulation is a well-established palliative therapy for medically resistant epilepsy. Neurostimulation, with newer devices and targets becoming available, is a rapidly expanding field in epileptology. Considerable development and research are still necessary before these newer techniques become the standard of care for the treatment of epilepsy. PMID:23896505

  3. Development and validation of sensitive spectrophotometric method for determination of two antiepileptics in pharmaceutical formulations

    NASA Astrophysics Data System (ADS)

    Gouda, Ayman A.; Malah, Zakia Al

    2013-03-01

    Rapid, sensitive and validated spectrophotometric methods for the determination of two antiepileptics (gabapentin (GAB) and pregabalin (PRG)) in pure forms and in pharmaceutical formulations was developed. The method is based on the formation of charge transfer complex between drug and the chromogenic reagents quinalizarin (Quinz) and alizarin red S (ARS) producing charge transfer complexes in methanolic medium which showed an absorption maximum at 571 and 528 nm for GAB and 572 and 538 nm for PRG using Quinz and ARS, respectively. The optimization of the reaction conditions such as the type of solvent, reagent concentration and reaction time were investigated. Beer's law is obeyed in the concentration ranges 0.4-8.0 and 0.5-10 μg mL-1 for GAB and PRG using Quinz and ARS, respectively. The molar absorptivity, Sandell sensitivity, detection and quantification limits are also calculated. The correlation coefficients were ⩾0.9992 with a relative standard deviation (RSD%) of ⩽1.76. The methods are successfully applied to the determination of GAB and PRG in pharmaceutical formulations and the validity assesses by applying the standard addition technique, which compared with those obtained using the reported methods.

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

    PubMed

    Story, Lachel; Butts, Janie B

    2010-05-01

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

  5. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  6. Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development

    PubMed Central

    Wahab, Abdul

    2010-01-01

    Epilepsy is a serious neurological disorder that affects around 50 million people worldwide. Almost 30% of epileptic patients suffer from pharmacoresistance, which is associated with social isolation, dependent behaviour, low marriage rates, unemployment, psychological issues and reduced quality of life. Currently available antiepileptic drugs have a limited efficacy, and their negative properties limit their use and cause difficulties in patient management. Antiepileptic drugs can provide only symptomatic relief as these drugs suppress seizures but do not have ability to cure epileptogenesis. The long term use of antiepileptic drugs is limited due to their adverse effects, withdrawal symptoms, deleterious interactions with other drugs and economic burden, especially in developing countries. Furthermore, some of the available antiepileptic drugs may even potentiate certain type of seizures. Several in vivo and in vitro animal models have been proposed and many new antiepileptic drugs have been marketed recently, but large numbers of patients are still pharmacoresistant. This review will highlight the difficulties in treatment and management of epilepsy and the limitations of available antiepileptic drugs and animal seizure models.

  7. Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development

    PubMed Central

    Wahab, Abdul

    2010-01-01

    Epilepsy is a serious neurological disorder that affects around 50 million people worldwide. Almost 30% of epileptic patients suffer from pharmacoresistance, which is associated with social isolation, dependent behaviour, low marriage rates, unemployment, psychological issues and reduced quality of life. Currently available antiepileptic drugs have a limited efficacy, and their negative properties limit their use and cause difficulties in patient management. Antiepileptic drugs can provide only symptomatic relief as these drugs suppress seizures but do not have ability to cure epileptogenesis. The long term use of antiepileptic drugs is limited due to their adverse effects, withdrawal symptoms, deleterious interactions with other drugs and economic burden, especially in developing countries. Furthermore, some of the available antiepileptic drugs may even potentiate certain type of seizures. Several in vivo and in vitro animal models have been proposed and many new antiepileptic drugs have been marketed recently, but large numbers of patients are still pharmacoresistant. This review will highlight the difficulties in treatment and management of epilepsy and the limitations of available antiepileptic drugs and animal seizure models. PMID:27713344

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

    PubMed Central

    Kiasalari, Zahra; Khalili, Mohsen; Roghani, Mehrdad; Heidari, Hamid; Azizi, Yaser

    2013-01-01

    Introduction Considering the prevalence of epilepsy and the failure of available treatments for many epileptic patients, finding more effective drugs in the treatment of epilepsy seems necessary. Oxidative stress has a special role in the pathogenesis of epileptic syndrome. Therefore, in the present study, we have examined the anti-epileptic and anti-oxidant properties of the Ferula Assa Foetida gum extract, using the pentylentetrazole (PTZ) kindling method. In this experimental study, sixty male Albino mice weighing 25-30 g were selected and were randomly divided into 6 groups. 1- the control group, 2- PTZ-kindled mice, 3- positive control group which received valproate (100 mg/kg) as anti-convulsant drug, 4-5 & 6- the groups of kindled mice that pretreated with 25, 50 and 100 mg/kg doses of Ferula Assa Foetida gum extract. Methods Kindling has been induced in all groups, except for the control group via 11 PTZ injections (35 mg /kg; ip) every other day for 22 days. In the 24th day, the PTZ challenge dose was injected (75 mg / kg) to all groups except the control group. The intensity of seizures were observed and noted until 30 minutes after PTZ injection. At list, the mice were decapitated and the brains of all the mice were removed.. and their biochemical factors levels including malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were determined. Results Results of this study show that Ferula Assa Foetida gum extract is able to reduce seizure duration and its intensity. In addition, this extract has reduced MDA and NO levels and increased the level of SOD in the brain tissue compared to the PTZ- kindled mice. Discussion It can be concluded that Ferula Assa Foetida gum extract, in specific doses, is able to show an anti-epileptic effect because of its antioxidant properties, probably acting through an enzyme activity mechanism. PMID:25337361

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

    PubMed Central

    Wolfart, Jakob; Laker, Debora

    2015-01-01

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

  10. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  11. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. 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. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  12. Direct photodegradation of lamotrigine (an antiepileptic) in simulated sunlight--pH influenced rates and products.

    PubMed

    Young, Robert B; Chefetz, Benny; Liu, Aiju; Desyaterik, Yury; Borch, Thomas

    2014-04-01

    Lamotrigine is an antiepileptic and mood stabilizing drug that has been detected in wastewater, groundwater, surface water and drinking water, at frequencies in surface water ranging from 47 to 97%. Because lamotrigine is a weak base (pKa = 5.7) that appears in two protonation states in natural waters, this study examined the direct photodegradation of lamotrigine (11.4 to 12.0 mg L(-1)) in simulated sunlight using liquid chromatography-UV diode array detection and buffered aqueous solutions at pH 3.3, 5.3, and 7.7. Lamotrigine's half-life varied little (100 ± 3 to 112 ± 2 h) with solution pH, but its specific light absorption rate was 12 times higher, and its reaction quantum yield was 13 times lower, at pH 7.7 versus pH 3.3. In the estimated midday, midsummer sunlight in Denver, CO, USA (latitude 39.8617 °N), lamotrigine's estimated photodegradation rate was more than twice as fast at pH 7.7 versus pH 3.3. Lamotrigine's photoproducts were detected by liquid chromatography-UV diode array detection and time-of-flight mass spectrometry. Solution pH was shown to affect the identities and relative abundances of lamotrigine's photoproducts. Some photoproducts appeared only in solutions containing protonated lamotrigine, and others appeared only in solutions containing neutral lamotrigine. As a result, different reaction mechanisms were proposed. Finally, lamotrigine's reaction quantum yield (2.51 ± 0.07 × 10(-5) mol einstein(-1) at pH 7.7) and other results suggested that lamotrigine and three photoproducts are approximately as resistant to direct photodegradation as carbamazepine, a frequently detected pharmaceutical in surface waters.

  13. Antiepileptic and Antioxidant Effect of Brassica nigra on Pentylenetetrazol-Induced Kindling in Mice.

    PubMed

    Kiasalari, Zahra; Khalili, Mohsen; Roghani, Mehrdad; Sadeghian, Azam

    2012-01-01

    Considering the high rate of epilepsy today, with respect to the insufficiency of the available therapies, new strategies and methods are recommended for medical treatment of epileptic patients. Therefore, the present study experimentally investigated the anticonvulsant effect of a herbal medicine candidate brassica nigra, by using kindling method. Sixty male mice were randomly selected and divided into six experimental groups (n = 10) including: 1-control, 2-pentylentetrazole (PTZ)-kindled mice, 3-positive control group received valproate (100 mg/Kg) as anti-convulsant drug, 4-5 and 6 received brassica nigra seed extract in three doses (75, 150 and 300 mg/Kg; IP). All groups except for the control ones were kindled by 11 period injections of PTZ (35 mg/Kg; IP). In the 12th injection, all groups except for the control group were tested for PTZ challenge dose (75 mg/Kg). However, the exhibited phases of seizure (0-6) were observed and noted till 30 min after the PTZ injection. At last, the brains of all the mice were removed and then malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) levels of the brain tissues were determined. Statistical analysis of the data shows that the seed extract could reduce the intensity, improvement and duration of seizure. In addition, the brassica nigra extract increased the SOD and NO levels and decreased the MDA level in the brain tissues. Attained results show that the extract of Brassica nigra seed can be used in grand mal seizure treatment. Moreover, the antiepileptic effect of this extract is probably caused by its antioxidant properties and acts via enzyme activity mechanism. PMID:24250555

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

    PubMed

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. This is part i of a comprehensive review on antiepileptic drug (AED) inducers using both mechanistic pharmacological and evidence-based medicine to provide practical recommendations to neurologists and psychiatrists concerning how to control for them. Carbamazepine, phenobarbital and phenytoin, are clinically relevant AED inducers; correction factors were calculated for studied induced drugs. These correction factors are rough simplifications for orienting clinicians, since there is great variability in the population regarding inductive effects. As new information is published, the correction factors may need to be modified. Some of the correction factors are so high that the drugs (e.g., bupropion, quetiapine or lurasidone) should not co-prescribed with potent inducers. Clobazam, eslicarbazepine, felbamate, lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin and valproic acid are grouped as mild inducers which may (i)be inducers only in high doses; (ii)frequently combine with inhibitory properties; and (iii)take months to reach maximum effects or de-induction, definitively longer than the potent inducers. Potent inducers, definitively, and mild inducers, possibly, have relevant effects in the endogenous metabolism of (i)sexual hormones, (ii) vitamin D, (iii)thyroid hormones, (iv)lipid metabolism, and (v)folic acid. PMID:25745819

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

    PubMed

    de Leon, Jose

    2015-01-01

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

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

    PubMed

    de Leon, Jose

    2015-01-01

    The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions. The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic enzymes such as CYPs and UGTs, and transporters such as P-gp, implies that the amount of these proteins increases when they are induced; this is almost always explained by increasing synthesis mediated by the so-called nuclear receptors (constitutive androstane, estrogen, glucocorticoid receptors and pregnaneX receptors). Although parti provides correction factors for AEDs, extrapolation from an average to an individual patient may be influenced by administration route, absence of metabolic enzyme for genetic reasons, and presence of inhibitors or other inducers. AED pharmacodynamic DDIs may also be important. Six patients with extreme sensitivity to AED inductive effects are described. PMID:26111722

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

    PubMed

    de Leon, Jose

    2015-01-01

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

  18. Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

    PubMed Central

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

    2014-01-01

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

  19. [Photic sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome].

    PubMed

    García-Moreno, J M

    2006-01-01

    Sneeze is an ubiquitous phenomenon that happens to everyone. In spite of this, little attention has been paid to it, among medical literature in general, and even less in neurologic texts. A curious entity, called photic sneeze reflex, solar sneeze reflex, light sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome, known perhaps since ancient Greek, has been scarcely described in the scientific literature, mainly as clinical notes and letters to the editor, but in a detailed way, we can find just a few reports. This reflex appears when subjects are exposed suddenly to intense sunlight and it consists of long incoercible sneeze bursts. It is usually ignored by its sufferers, who report it as a curiosity or a minor complaint, and its importance has been neglected in spite of its hereditary nature and its apparently high prevalence. We review the history, epidemiology, genetics, neuroanatomy, neurophysiology and physiopathology of this reflex hereditary response.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. [Photic sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome].

    PubMed

    García-Moreno, J M

    2006-01-01

    Sneeze is an ubiquitous phenomenon that happens to everyone. In spite of this, little attention has been paid to it, among medical literature in general, and even less in neurologic texts. A curious entity, called photic sneeze reflex, solar sneeze reflex, light sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome, known perhaps since ancient Greek, has been scarcely described in the scientific literature, mainly as clinical notes and letters to the editor, but in a detailed way, we can find just a few reports. This reflex appears when subjects are exposed suddenly to intense sunlight and it consists of long incoercible sneeze bursts. It is usually ignored by its sufferers, who report it as a curiosity or a minor complaint, and its importance has been neglected in spite of its hereditary nature and its apparently high prevalence. We review the history, epidemiology, genetics, neuroanatomy, neurophysiology and physiopathology of this reflex hereditary response. PMID:16525923

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

    PubMed

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

    2016-04-01

    A description of a case is presented of an isolated hypofibrinogenaemia acquired in relation to taking topiramate used as concomitant treatment of a drug resistant epilepsy. The hypofibrinogenaemia developed in the course of a month after the introduction of the drug, and was diagnosed in the perioperative period. PMID:26386515

  3. Search and Rescue Operations of Aircraft in Africa: Some Compelling Issues

    NASA Technical Reports Server (NTRS)

    Abeyratne, Ruwantissa I. R.

    2002-01-01

    The world aviation community has felt the compelling need for a well-coordinated global programme for search and rescue operations of aircraft ever since commercial aviation was regulated in 1944. Guidelines and plans of action for search and rescue have therefore been considered critical in the event of an aircraft accident. This fact is eminently brought to bear in the continental regions of Africa and South America in particular, where vast expanses of land are still uninhabited or sparsely populated and controlled flight into terrain (CFIT-where an aircraft may crash on land while still under the control of technical crew) is a common occurrence. There are numerous guidelines that have been adopted under the umbrella of the International Civil Aviation Organization which are already in place for the provision of search and rescue operations pertaining to aircraft. However, when an accident occurs in the territory of a State, there are sensitivities involving the State in which the aircraft concerned was registered and issues of sovereignty which have to be considered. Additionally. issues such as the voluntary nature of the search and rescue services offered. confidentiality, timeliness of such operations, fairness and uniformity all play a critical role. This article addresses the issue of search and rescue operations in Africa and examines in some detail where the world aviation community is right now and where it is headed in this important field of human endeavour.

  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

    PubMed Central

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

    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 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. PMID:25878976

  5. Tracking the Temporal Evolution of a Perceptual Judgement Using a Compelled-Response Task

    PubMed Central

    Shankar, Swetha; Massoglia, Dino P.; Zhu, Dantong; Costello, M. Gabriela; Stanford, Terrence R.; Salinas, Emilio

    2011-01-01

    Choice behavior and its neural correlates have been intensely studied with tasks in which a subject makes a perceptual judgement and indicates the result with a motor action. Yet, a question crucial for relating behavior to neural activity remains unresolved: what fraction of a subject’s reaction time (RT) is devoted to the perceptual evaluation step, as opposed to executing the motor report? Making such timing measurements accurately is complicated because RTs reflect both sensory and motor processing, and because speed and accuracy may be traded. To overcome these problems, we designed the compelled-saccade task, a two-alternative forced-choice task in which the instruction to initiate a saccade precedes the appearance of the relevant sensory information. With this paradigm, it is possible to track perceptual performance as a function of the amount of time during which sensory information is available to influence a subject’s choice. The result — the tachometric curve — directly reveals a subject’s perceptual processing capacity independently of motor demands. Psychophysical data, together with modeling and computer-simulation results, reveal that task performance depends on three separable components: the timing of the motor responses, the speed of the perceptual evaluation, and additional cognitive factors. Each can vary quickly, from one trial to the next, or can show stable, longer-term changes. This novel dissociation between sensory and motor processes yields a precise metric of how perceptual capacity varies under various experimental conditions, and serves to interpret choice-related neuronal activity as perceptual, motor, or both. PMID:21653845

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

    PubMed

    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

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

    ERIC Educational Resources Information Center

    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…

  8. Girls' Sexual Development in the Inner City: From Compelled Childhood Sexual Contact to Sex-for-Things Exchanges

    ERIC Educational Resources Information Center

    Dunlap, Eloise; Golub, Andrew; Johnson, Bruce D.

    2003-01-01

    Child Sexual Abuse (CSA) has been linked to a wide variety of adverse psychological and behavioral outcomes. This paper describes girls' sexual development in the inner city based on qualitative material from a long-term ethnographic (observational) study. For many inner-city girls, early and then continued experiences of being compelled to have…

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

  12. Cost-effectiveness analysis of antiepileptic drugs in the treatment of Lennox-Gastaut syndrome.

    PubMed

    Clements, Karen M; Skornicki, Michelle; O'Sullivan, Amy K

    2013-10-01

    An economic model evaluated the costs and outcomes of adjunctive clobazam therapy for Lennox-Gastaut syndrome (LGS) compared with adjunctive lamotrigine, rufinamide, and topiramate. Clinical data were used to estimate baseline frequency and the percentage of drop-seizure reductions over 3 months (all comparators) and 2 years (rufinamide). Claims data from a large US health care plan were employed to estimate costs. After 3 months, 21.5% of those receiving clobazam were drop-seizure-free. Over a 3-month horizon, clobazam was more effective and less expensive than comparators, with the assumption that >0.77% of drop seizures required medical care. Below this threshold, topiramate was less costly than clobazam. With the base-case assumption that 2.3% of drop seizures were medically attended, costs for patients receiving clobazam totaled $30,147 versus $34,223-$35,378 for comparators. Clobazam was more efficacious and less costly than rufinamide over a 2-year horizon. The percentage of medically attended drop seizures was a driver of results. Clobazam treatment may be cost-saving. PMID:23973644

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  19. The involvement of neuronal nitric oxide synthase in the anti-epileptic action of curcumin on pentylenetetrazol-kindled rats.

    PubMed

    Zhu, Wenting; Su, Jing; Liu, Jing; Jiang, Changbin

    2015-01-01

    In this study, it was investigated whether a NO signaling pathway is involved in the anti-epileptic effect of curcumin on pentylenetetrazol (PTZ)-kindled rats. PTZ-kindled rats received different doses of curcumin that were administered intraperitoneally for 24 days. Either a non-selective inhibitor of nitric oxide synthase (NOS) (N-nitro-L-arginine methyl ester (L-NAME)), a selective inhibitor of neuronal NOS (7-Nitroindazole (7-NI)), a selective inhibitor of inducible NOS (aminoguanidine (AG)), or a NO precursor (L-arginine (L-ARG)) was administered chronically to evaluate the role of NO in curcumin's anti-seizure effect. A chronic administration of curcumin (200 mg/kg) was most effective for decreasing the mean frequency of epileptiform discharge. Furthermore, a pretreatment with L-NAME or 7-NI augmented the anti-epileptic effect of curcumin. In contrast, AG failed to significantly alter the anti-epileptic effect of curcumin. A pretreatment with L-ARG temporally reversed the anti-epileptic effect of curcumin in the early stage, but in the late stage, it potentiated curcumin's anti-epileptic effect. These findings suggest that the L-arginine-nitric oxide pathway may be involved in the anti-epileptic properties of curcumin, and that the role of nNOS (and not iNOS) is prominent in this neuroprotective feature. PMID:26406082

  20. Evaluation of antiepileptic activity of chloroform extract of Acalypha fruticosa in mice

    PubMed Central

    Govindu, Sumalatha; Adikay, Sreedevi

    2014-01-01

    Aim: The aim of the present study is to evaluate the antiepileptic activity of chloroform extract of aerial parts of Acalypha fruticosa in mice. Materials and Methods: The antiepileptic activity of chloroform extract of A. fruticosa at the doses of 30, 100 and 300 mg/kg, p.o. was evaluated by maximum electroshock (MES), pentylenetetrazole (PTZ) and isoniazid (INH)-induced convulsions in mice. Statistical analysis was carried out by one-way analysis of variance followed by Dunnett's test. Results: In MES method, the chloroform extract significantly protected the mice from convulsions induced by electroshock method in a dose-dependent manner and exhibited more activity at the dose of 300 mg/kg when compared with diazepam treated animals. In PTZ method, the extract inhibited convulsions in mice potent than phenobarbitone sodium. In INH method, it delayed the latency of convulsions in mice in a dose-dependent manner but failed to protect the mice against mortality. Conclusion: The chloroform extract exhibited significant and dose-dependent antiepileptic activity, which may be due to the presence of antioxidant principles like flavanoids. PMID:24761113

  1. Compel Students to Read with Compelling Nonfiction

    ERIC Educational Resources Information Center

    Kelsey, Marie

    2011-01-01

    To cover everything, they often must race through mandated chunks of content knowledge, making it impossible for students to savor and reflect on any new ideas that might motivate them to read personally interesting materials outside of class. This is a lost opportunity for students to engage in authentic reading and learning on their own terms.…

  2. AEDS and Psychotropic Drugs in Children with Autism and Epilepsy

    ERIC Educational Resources Information Center

    Tuchman, Roberto

    2004-01-01

    The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in…

  3. Antiepileptic and antipsychotic activities of standardized Śilājatu (Shilajit) in experimental animals

    PubMed Central

    Durg, Sharanbasappa; Veerapur, Veeresh P.; Thippeswamy, B. S.; Ahamed, Syed Mansoor

    2015-01-01

    Background: Śilājatu (Shilajit; SJ) is claimed in traditional Indian medical practice to be useful in the treatment of nervous disorders, epilepsy and as antistress. Aim: To investigate whether SJ possesses antiepileptic and antipsychotic activities in rodents. Materials and Methods: Isonicotinyl hydrazine (INH), pentylenetetrazole (PTZ), apomorphine, phenytoin, diazepam, haloperidol and other chemicals of analytical grade were procured from standard companies. The antiepileptic activity of SJ was assessed using maximal electro shock (MES)-induced seizures in rats, INH and PTZ-induced seizures in mice. The antipsychotic effect of SJ was evaluated using apomorphine-induced climbing and stereotyped behaviours respectively, in mice and rats. Settings and Designs: SJ (25 and 50 mg/kg, p.o.) was given orally once daily for 15 days in all the rodent models. On the test day, SJ was administered 1 h prior to electric shock or chemical inducers (INH/PTZ/apomorphine) in experimental animals; the animals were then observed for different phases of seizures and psychotic behaviours. In addition, gamma-aminobutyric acid (GABA) content in the brain of rats and mice was estimated in seizure models. Statistical Analysis: The data were expressed as mean ± standard error of mean. Statistical comparisons were performed by one-way ANOVA followed by Tukey's post-test using Graph Pad Prism version 5.0, USA. A P < 0.05 was considered significant. Results and Conclusions: SJ pretreatment significantly inhibited the seizures induced by MES, INH and PTZ in a dose dependent manner. Further, SJ augmented brain GABA levels to normal, decreased by INH and PTZ in mice brain. SJ pretreatment also significantly inhibited the climbing and stereotyped behaviours induced by apomorphine. The present data seems to confirm the antiepileptic activity of SJ which may be because of enhancing the GABAergic system. The antipsychotic activity observed may be due to anti-dopaminergic and/or GABA

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

    PubMed

    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.

  5. Levetiracetam induced psoriasiform drug eruption: a rare case report.

    PubMed

    Gencler, Onur Serdar; Gencler, Bilgen; Altunel, Cemile Tugba; Arslan, Nur

    2015-11-01

    Levetiracetam (LEV) is an established second generation anti-epileptic drug and LEV associated severe cutaneous reactions are rare. Here we report the case of psoriasiform drug eruption in a patient with newly diagnosed epilepsy who had been treated with levetiracetam. To our knowledge this is the first report of a patient with a psoriasiform eruption that appeared after the administration of LEV. PMID:26702269

  6. [Therapeutic drug monitoring of rufinamide].

    PubMed

    Bentué-Ferrer, Danièle; Tribut, Olivier; Verdier, Marie-Clémence

    2012-01-01

    Rufinamide is a third-generation antiepileptic drug, available since early 2010 in France. It is indicated in combination therapy in the Lennox-Gastaut syndrome from the age of 4. It has orphan drug status. The bioavailability of rufinamide is high, but decreases with the dose and increases with food intake. Rufinamide is not metabolized by cytochromes but hydrolyzed by a carboxylesterase in an inactive carboxylic derivative. Elimination is mainly renal. The half-life varies from 6 to 10h. Although established from relatively few studies, exposure efficacy and exposure toxicity relationships are argued. A plasma concentration of 15 mg/L, obtained with a standard regimen, reduces the number of seizures of 25%. Few factors of intrinsic variability are described. There are few clinically significant pharmacokinetic interactions and they concern combinations with other antiepileptic drugs, especially valproate. Although there is no validated therapeutic range, the level of evidence for this therapeutic drug monitoring has been estimated at "possibly useful". PMID:22850104

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

    PubMed Central

    Lee, Jinsoo; Son, Kwanghyun; Hwang, Gwiseo

    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

  8. Compelling Diversity through Discrimination

    ERIC Educational Resources Information Center

    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…

  9. Antiarrhythmic drugs and epilepsy.

    PubMed

    Borowicz, Kinga K; Banach, Monika

    2014-08-01

    For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDEP) has most likely a cardiac mechanism. Common elements of pathogenesis create a basis for the assumption that antiarrhythmic drugs (AADs) may affect seizure phenomena and interact with antiepileptic drugs (AEDs). Numerous studies have demonstrated anticonvulsant effects of AADs. Among class I AADs (sodium channel blockers), phenytoin is an established antiepileptic drug. Propafenone exerted low anti-electroshock activity in rats. Lidocaine and mexiletine showed the anticonvulsant activity not only in animal models, but also in patients with partial seizures. Among beta-blockers (class II AADs), propranolol was anticonvulsant in models for generalized tonic-clonic and complex partial seizures, but not for myoclonic convulsions. Metoprolol and pindolol antagonized tonic-clonic seizures in DBA/2 mice. Timolol reversed the epileptiform activity of pentylenetetrazol (PTZ) in the brain. Furthermore, amiodarone, the representative of class III AADs, inhibited PTZ- and caffeine-induced convulsions in mice. In the group of class IV AADs, verapamil protected mice against PTZ-induced seizures and inhibited epileptogenesis in amygdala-kindled rats. Verapamil and diltiazem showed moderate anticonvulsant activity in genetically epilepsy prone rats. Additionally, numerous AADs potentiated the anticonvulsant action of AEDs in both experimental and clinical conditions. It should be mentioned, however, that many AADs showed proconvulsant effects in overdose. Moreover, intravenous esmolol and intra-arterial verapamil induced seizures even at therapeutic dose ranges. PMID:24948053

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

    PubMed

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

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. PMID:27324073

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

    PubMed

    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.

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

    PubMed

    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. PMID:26204087

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

    PubMed

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

    2011-01-01

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

  14. Drug hypersensitivity syndrome.

    PubMed

    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.

  15. Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

    PubMed Central

    Xiong, Jie; Mao, Ding-an; Liu, Li-qun

    2015-01-01

    The pathogenesis of intractable epilepsy is not fully clear. In recent years, both animal and clinical trials have shown that the expression of ATP-binding cassette (ABC) transporters is increased in patients with intractable epilepsy; additionally, epileptic seizures can lead to an increase in the number of sites that express ABC transporters. These findings suggest that ABC transporters play an important role in the drug resistance mechanism of epilepsy. ABC transporters can perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs, thus causing resistance to antiepileptic drugs. Given the important role of ABC transporters in refractory epilepsy drug resistance, antiepileptic drugs that are not substrates of ABC transporters were used to obtain ABC transporter inhibitors with strong specificity, high safety, and few side effects, making them suitable for long-term use; therefore, these drugs can be used for future clinical treatment of intractable epilepsy. PMID:26491660

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

    PubMed

    Gao, Lan; Li, Shuchuen

    2016-01-01

    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. PMID:27217762

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

    PubMed Central

    Gao, Lan; Li, Shuchuen

    2016-01-01

    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. PMID:27217762

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

    PubMed

    Huang, Yanyun; Gauvreau, Henry; Harding, John

    2012-01-01

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

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

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

  1. The Anti-Epileptic Drug Valproic Acid (VPA) Inhibits Steroidogenesis in Bovine Theca and Granulosa Cells In Vitro

    PubMed Central

    Glister, Claire; Satchell, Leanne; Michael, Anthony E.; Bicknell, Andrew B.; Knight, Philip G.

    2012-01-01

    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 (P<0.0001) both basal (70% suppression; IC50 67±10 µg/ml) and LH-induced (93% suppression; IC50 58±10 µg/ml) androstenedione secretion by TC. VPA reduced CYP17A1 mRNA abundance (>99% 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. PMID:23152920

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

    PubMed

    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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. Assessment of quality of life in epilepsy patients receiving anti-epileptic drugs in a tertiary care teaching hospital

    PubMed Central

    Pimpalkhute, Sonali A.; Bajait, Chaitali S.; Dakhale, Ganesh N.; Sontakke, Smita D.; Jaiswal, Kavita M.; Kinge, Parag

    2015-01-01

    Objectives: Health-related quality of life (QOL) is an important outcome in epilepsy treatment. Very few studies have been carried out on the quality of life in epilepsy (QOLIE-31) in India. The present study aimed to determine the level of health-related QOLIE-31 in patients of epilepsy. Materials and Methods: This was a cross-sectional, questionnaire-based study conducted in a tertiary care teaching hospital. Respondents were adults aged at least 18-year-old with a diagnosis of epilepsy. QOLIE-31 was used for collecting data on health-related QOL. The unpaired t-test or one-way analysis of variance was used to compare means of QOL scores between groups. Results: Totally, 60 patients of epilepsy were included in the study. The mean (standard deviation) total score of QOLIE-31 was 64.61. A score of cognitive and medication effect were significantly better in carbamazepine group as compared to valproate group. Conclusions: Patients on monotherapy had a better QOL as compared to patients receiving polytherapy. PMID:26600647

  5. Efficacy of rufinamide in drug-resistant epilepsy: a meta-analysis.

    PubMed

    Verrotti, Alberto; Loiacono, Giulia; Ballone, Enzo; Mattei, Peter A; Chiarelli, Francesco; Curatolo, Paolo

    2011-05-01

    Rufinamide is a new orally active antiepileptic drug that has been found to be effective in the treatment of partial seizures and drop attacks associated with Lennox-Gastaut syndrome. We performed a quantitative analysis of the efficacy of this new antiepileptic drug from all double-blind, add-on, randomized, placebo-controlled clinical trials published to date. Data from 918 patients were studied. The number of patients per study varied from 25 to 262. Rufinamide was efficacious in doses up to 45 mg/kg daily when provided as adjunctive therapy in patients with Lennox-Gastaut syndrome and other drug-resistant epilepsies. Further studies are needed to confirm and expand these findings. PMID:21481742

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

    PubMed

    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.

  7. Effects of the antiepileptics phenytoin and zonisamide on dentin formation and bone mineral density of the mandible in growing rats.

    PubMed

    Takahashi, A; Saito, T; Mayanagi, H; Kamei, J; Onodera, K

    2004-12-01

    This study was undertaken to examine the effects of the antiepileptics phenytoin and zonisamide on changes in the mineral density of the incisor and bone mineral density (BMD) of the mandibular head, and on the rate of dentin formation using histomorphometric measurements. After repeated administration of phenytoin or zonisamide to male growing rats, the mineral density of the lower incisors and mandibular head were determined by analyzing microradiographs and dentin formation rates were determined by histomorphometric measurements. Results showed a significant decrease in the mean values of BMD of the mandibular head and lower incisors in groups treated with phenytoin or zonisamide compared with the vehicle-treated group (p < 0.05). The percent rates of decrease in mineral density of the incisors for phenytoin and zonisamide were 6.8% and 4.0%, respectively. Phenytoin and zonisamide significantly reduced the dentin formation rate for the mesial and distal areas compared with the vehicle-treated group. Thus, epileptic children who are treated over a long period with antiepileptics, especially at primary school age, should ensure good oral hygiene so as not to suffer bone loss, edentulism or gingival overgrowth. PMID:15672119

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

    PubMed

    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.

  9. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

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

    PubMed

    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

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

    PubMed

    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.

  12. Health care organization drug testing.

    PubMed

    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.

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

    PubMed Central

    Huang, Long-Sun; Gunawan, Christian; Yen, Yi-Kuang; Chang, Kai-Fung

    2015-01-01

    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. PMID:25632826

  14. Nanotechnology for the Delivery of Drugs to the Brain for Epilepsy

    PubMed Central

    Bennewitz, Margaret F.; Saltzman, W. Mark

    2009-01-01

    Epilepsy results from aberrant electrical activity that can affect either a focal area or the entire brain. In treating epilepsy with drugs, the aim is to decrease seizure frequency and severity while minimizing toxicity to the brain and other tissues. Antiepileptic drugs (AEDs) are usually administered by oral and intravenous (IV) routes, but these drug treatments are not always effective. Drug access to the brain is severely limited by a number of biological factors, particularly the blood-brain barrier (BBB), which impedes the ability of AEDs to enter and remain in the brain. To improve the efficacy of AEDs, new drug delivery strategies are being developed; these methods fall into the three main categories: drug modification, BBB modification, and direct drug delivery. Recently, all three methods have been improved through the use of drug-loaded nanoparticles. PMID:19332327

  15. Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives.

    PubMed

    Prakash, Chinnasamy Rajaram; Raja, Sundararajan

    2011-12-01

    Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5c, 5g, 5j and 5n were found active in MES model, while 5o showed significant antiepileptic activity in scPTZ model. Further all these five compounds were administered orally to rats, 5c, 5g and 5n showed better activity than Phenytoin in oral route. Among these compounds 5c revealed protection in MES at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration respectively. This molecule provided also protection in the scPTZ at a dose of 300 mg/kg in both time intervals. PMID:22037252

  16. Meditation improves clinicoelectroencephalographic measures in drug-resistant epileptics.

    PubMed

    Deepak, K K; Manchanda, S K; Maheshwari, M C

    1994-03-01

    Eleven adults suffering from drug-resistant epilepsies were given meditation practice, while another nine adults acted as waiting list controls. All patients were on antiepileptic drugs and their serum drug levels were monitored regularly. Patients in the intervention group were given training in meditation, and they practiced meditation 20 minutes a day for one year. They showed a significant reduction in seizure frequency and duration, an increase in the dominant background EEG frequency, a reduction in mean spectral intensity of the 0.7-7.7 Hz segment, and an increment in mean spectral intensity in the 8-12 Hz segment of the EEG. All changes were statistically significant. Control patients did not show significant changes in seizure frequency and duration during the observation period of one year. The results indicate that continued meditation practice is of substantial help in improving the clinicoelectrographic picture in drug-resistant epileptics.

  17. Flurbiprofen-induced generalized bullous fixed drug eruption.

    PubMed

    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.

  18. Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies.

    PubMed

    Barros, Walleska Bismaida Zacarias Galvão; da Silva, Allysson Haide Queiroz; Barbosa, Ana Soraya Lima; Nunes, Ábner Magalhães; Reys, José Rui Machado; de Araújo-Filho, Heitor Gomes; de Souza Siqueira Quintans, Jullyana; Quintans-Júnior, Lucindo José; Pfeffer, Michel; Dos Santos Malta, Valéria Rodrigues; Meneghetti, Mario Roberto

    2016-02-01

    We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy.

  19. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  20. Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication.

    PubMed

    Macphee, G J; Larkin, J G; Butler, E; Beastall, G H; Brodie, M J

    1988-01-01

    Impairment of libido and sexual potency are commonly reported by male epileptic patients. This may be partly a consequence of medication. Circulating hormones were measured in 53 postpubertal male epileptic patients less than 45 years of age and in an age-matched control group (n = 40), consisting of 14 untreated epileptic patients and 26 unmedicated healthy subjects. A subgroup also underwent a combined gonadotrophin- and thyrotrophin-releasing hormone (LH-RH/TRH) pituitary stimulation test. Untreated patients did not differ from healthy subjects for any parameter, and their data were combined for comparison with the treated epileptic patients. Total testosterone (T), androstenedione, and basal follicle-stimulating hormone concentrations were similar in all patient groups. Patients receiving more than one drug had higher sex hormone binding globulin (SHBG) (p less than 0.01) and lower free T and dehydroepiandrosterone sulphate (DHAS) levels (both p less than 0.001) than controls. Carbamazepine (CBZ) monotherapy also reduced free T (p less than 0.05) and DHAS (p less than 0.001) and increased basal prolactin (p less than 0.01). In these two groups of patients, basal luteinising hormone (LH) was elevated (p less than 0.01), presumably as a pituitary response to increased T catabolism. There was a negative correlation between free T and circulating CBZ (r = -0.54, p less than 0.05) in the monotherapy patients. Phenytoin (PHT) was associated with a rise in SHBG (p less than 0.01) and a fall in DHAS (p less than 0.001). Basal LH was also elevated, but this just failed to reach statistical significance (p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Derangements in bone mineral parameters and bone mineral density in south Indian subjects on antiepileptic medications

    PubMed Central

    Koshy, George; Varghese, Ron Thomas; Naik, Dukhabandhu; Asha, Hesargatta Shyamsunder; Thomas, Nihal; Seshadri, Mandalam Subramaniam; Alexander, Mathew; Thomas, Maya; Aaron, Sanjith; Paul, Thomas Vizhalil

    2014-01-01

    Background: Although there are reports describing the association of alternations of bone and mineral metabolism in epileptic patients with long-term anticonvulsant therapy, there are only limited Indian studies which have looked at this aspect. Objectives: This study was done to compare the prevalence of changes in bone mineral parameters and bone mineral density (BMD) in ambulant individuals on long-term anticonvulsant therapy with age- and body mass index (BMI)-matched healthy controls. Materials and Methods: There were 55 men (on medications for more than 6 months) and age- and BMI-matched 53 controls. Drug history, dietary calcium intake (DCI), and duration of sunlight exposure were recorded. Bone mineral parameters and BMD were measured. Results: The control group had a significantly higher daily DCI with mean ± SD of 396 ± 91 mg versus 326 ± 101 mg (P = 0.007) and more sunlight exposure of 234 ± 81 vs 167 ± 69 min (P = 0.05). BMD at the femoral neck was significantly lower in cases (0.783 ± 0.105 g/cm2) when compared to controls (0.819 ± 0.114 g/cm2). Majority of the patients (61%) had low femoral neck BMD (P = 0.04). There was no significant difference in the proportion of subjects with vitamin D deficiency (<20 ng/mL) between cases (n = 32) and controls (n = 37) (P = 0.234). Conclusions: Vitamin D deficiency was seen in both the groups in equal proportions, highlighting the existence of a high prevalence of this problem in India. Low femoral neck BMD found in cases may stress the need for supplementing calcium and treating vitamin D deficiency in this specific group. However, the benefit of such intervention has to be studied in a larger proportion of epileptic patients. PMID:25221394

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

    PubMed

    Tamrazi, Benita; Almast, Jeevak

    2012-01-01

    Drug abuse is a substantial problem in society today and is associated with significant morbidity and mortality. Various drugs are associated with serious complications affecting the brain, and it is critical to recognize the imaging findings of these complications to provide prompt medical management. The central nervous system (CNS) is a target organ for drugs of abuse as well as specific prescribed medications. Drugs of abuse affecting the CNS include cocaine, heroin, alcohol, amphetamines, toluene, and cannabis. Prescribed medications or medical therapies that can affect the CNS include immunosuppressants, antiepileptics, nitrous oxide, and total parenteral nutrition. The CNS complications of these drugs include neurovascular complications, encephalopathy, atrophy, infection, changes in the corpus callosum, and other miscellaneous changes. Imaging abnormalities indicative of these complications can be appreciated at both magnetic resonance (MR) imaging and computed tomography (CT). It is critical for radiologists to recognize complications related to drugs of abuse as well as iatrogenic effects of various medications. Therefore, diagnostic imaging modalities such as MR imaging and CT can play a pivotal role in the recognition and timely management of drug-related complications in the CNS. PMID:22582355

  3. Reflection of Socioeconomic Changes in Wastewater: Licit and Illicit Drug Use Patterns.

    PubMed

    Thomaidis, Nikolaos S; Gago-Ferrero, Pablo; Ort, Christoph; Maragou, Niki C; Alygizakis, Nikiforos A; Borova, Viola L; Dasenaki, Marilena E

    2016-09-20

    The economic crisis plaguing Greece was expected to impact consumption of pharmaceuticals and illicit drugs - a priori to an unknown extent. We quantified the change of use for various classes of licit and illicit drugs by monitoring Athens' wastewater from 2010 to 2014. A high increase in the use of psychoactive drugs was detected between 2010 and 2014, especially for antipsychotics (35-fold), benzodiazepines (19-fold), and antidepressants (11-fold). This directly reflects the perceived increase of incidences associated with mental illnesses in the population, as a consequence of severe socioeconomic changes. Other therapeutic classes, like antiepileptics, hypertensives, and gastric and ulcer drugs also showed an increase in use (from 2-fold increase for antiepileptics to 13-fold for hypertensives). In contrast, the overall use of antibiotics and NSAIDs decreased. For mefenamic acid, an almost 28-fold decrease was observed. This finding is likely related to the reduction in drug expenditure applied in public health. A 2-fold increase of methamphetamine use was detected, associated with a cheap street drug called ″sisa″ (related to marginal conducts), which is a health concern. MDMA (5-fold) and methadone (7-fold) use showed also an increase, while cocaine and cannabis estimates did not show a clear trend. PMID:27556594

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

    PubMed Central

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

    2016-01-01

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

  5. Investigational new drugs for focal epilepsy.

    PubMed

    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.

  6. Investigational new drugs for focal epilepsy.

    PubMed

    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

  7. Drug allergies

    MedlinePlus

    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 ...

  8. Drug-induced status epilepticus.

    PubMed

    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

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

    PubMed

    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.

  10. Comparative Pre-Emptive Analgesic Efficacy Study of Novel Antiepileptic Agents Lamotrigine and Topiramate in Patients Undergoing Major Surgeries at a Tertiary Care Hospital: A Randomized Double Blind Clinical Trial

    PubMed Central

    Gupta, Ankush; Bhosale, Uma A.; Shah, Priyank; Yegnanarayan, Radha; Sardesai, Shalini

    2016-01-01

    Background Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy. Purpose This study is designed to study and compare the pre-emptive analgesic efficacy of Lamotrigine, Topiramate, and Diclofenac sodium in postoperative pain control. Methods This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated to control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's and pain scores were recorded using the Visual Analog Scale, Facial and Behavioral Rating Scale at awakening and at 1, 2, 4, 6, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Results Significantly higher pain scores were observed in the Topiramate group postoperatively for 2 h on all pain scales (p < 0.05), whereas in the control group it was significantly higher at 1 h (p < 0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p < 0.05) postoperative analgesic requirement. Conclusions Study results strongly suggest the pre-emptive analgesic efficacy of a single oral dose of Lamotrigine over Diclofenac and Topiramate in postoperative pain control. PMID:27721585

  11. Drug Safety

    MedlinePlus

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

  12. Drug disposition and hepatotoxicity in the elderly.

    PubMed

    Schenker, S; Bay, M

    1994-04-01

    Overall, the aged liver seems to function remarkably well in the elderly. Decreased drug disposition is selective and modest and there is no compelling evidence of greater susceptibility to drug-induced or other types of injury. Drug-drug interactions and concurrent derangements accompanying advanced age may, however, contribute to adverse drug effects. Still, the aged, consume about three times as many therapeutic agents as other people. Most of these are metabolized in the liver before excretion. With increasing age, hepatic blood flow falls and so does hepatic volume. Moreover, binding of some agents normally carried on albumin may decrease. In contrast, increasing age has relatively modest effects on hepatic drug metabolism and these are highly selective. In the healthy aged, hepatic drug elimination is only modestly, if at all, impaired and this is likely to especially affect agents dependent on liver blood flow. Other factors that affect drug elimination in the aged are drug-drug interaction and the frailty and functional impairment of many elderly, as a result of poor diet, infection, multiple hospitalizations, or other events. Decreased host defense systems in the aged liver may lead to decreased adaptation to stress and slower regeneration after injury.

  13. Unintentional poisoning with drugs in a Mexican pediatric population.

    PubMed

    Olguin, Hugo Juárez; Garduño, Lina Barranco; Pérez, Janett Flores; Pérez, Carmen Flores

    2011-01-01

    In Mexico, more than 70 % of acute pediatric poisoning is caused by medicines. The age groups at greatest risk of drug poisoning are those between 2 to 5 years and 14 to 18 years; although in this last group, drug ingestion is usually intentional. The purpose of our study was to determine the frequency of unintentional drug poisoning in the pediatric population attended in a tertiary care hospital in Mexico, and to review the rescue procedures applied in specific cases. A retrospective and descriptive study was performed through revision of clinical records, obtained from patients attended at the National Pediatrics Institute from January 1995 to June 2005. One hundred and thirty nine (139) records, 62 females and 77 males, median age 2 years with clinical diagnosis of drug poisoning were reviewed. Poisoning was confirmed in 23.7% of the cases by determination of drug plasma concentration. The most frequent causes of drug poisoning were analgesics (42.3 %), from which 60 % corresponded to acetylsalicylic acid and 40 % to acetaminophen; antiepileptics (22.9 %), anxiolytics (17.9 %) and other drugs (16.3 %). From our results, we concluded that self-medication was unlikely due to the early age of patients, unless ingestion of the drug was accidental. No case needed more than 24 h of hospitalization, and no patient died due to poisoning. Specific cause of poisoning was that, at early ages, doses must be administered according to the infant's weight, which poses a risk of poisoning. PMID:21471606

  14. Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 1959-2009.

    PubMed

    Shorvon, Simon D

    2009-03-01

    The drug therapy of epilepsy evolved enormously in this 50 year period. Advances in therapeutics included the incorporation of pharmacokinetics into clinical practice, enormous advances in neurochemistry, a trend to antiepileptic drug monotherapy, better drug assessment, better understanding of therapeutic outcomes, and the recognition of the large epilepsy treatment gap in many countries. An unprecedented range of new drugs was introduced in this period. Before 1989, these included carbamazepine, valproate, ethosuximide, and the benzodiazepines. Since 1989, 13 more new drugs have been licensed and marketed and there are others in the pipeline. The International League Against Epilepsy and its leading figures have played an important role in these developments. In this period, too, there has been a rapid expansion in research and development within the pharmaceutical industry and a rise in the value of the antiepileptic drug market. In parallel, governmental regulation of pharmaceuticals has greatly increased. To what extent the overall prognosis of epilepsy has improved as a result of these activities is an interesting and perplexing question. PMID:19298435

  15. Drug targets of migraine and neuropathy: treatment of hyperexcitability.

    PubMed

    Vécsei, László; Majláth, Zsófia; Balog, Anna; Tajti, János

    2015-01-01

    Migraine and neuropathic pain are common causes of chronic pain. The exact pathomechanism has not been fully clarified for either disorder, but their pathophysiological backgrounds involve several similar mechanisms. Peripheral sensitization occurs in the neuronal elements of the dorsal root ganglion or the trigeminal ganglion, while central sensitization appears in the second-order neurons in the dorsal horn of the spinal cord or the trigeminal nucleus caudalis. Central neuronal hyperexcitability has been implicated in both disorders, and the emerging evidence suggests alterations in the glutamatergic neurotransmission and N-methyl-D-aspartate-receptor activation. Migraine and neuropathic pain additionally share certain clinical features, such as enhanced sensitivity to sensory stimuli and cutaneous allodynia. The pharmacotherapy of both diseases is often challenging, but several antiepileptic drugs that target hyperexcitability are beneficial for both migraine and neuropathic pain. Kynurenine pathway metabolites are capable of influencing the glutamate receptors, and might therefore be novel candidates for future drug development.

  16. Does antiepileptic drug withdrawal predispose patients undergoing temporal lobe epilepsy surgery to late onset of psychiatric morbidity? A report of three cases

    PubMed Central

    Shukla, Garima; Agarwal, Priya; Sagar, Rajesh; Sood, Mamta; Gupta, Aditya; Suri, Ashish; Garg, Ajay

    2016-01-01

    Surgery is an established and increasingly utilized treatment option in medically refractory temporal lobe epilepsy. Many psychiatric problems are known to complicate in the postoperative period. Most studies have a follow-up period of less than 24 months. We report the cases of three patients who developed severe psychiatric problems in the late postoperative period after successful temporal lobectomy for refractory epilepsy — Psychosis, major depression with psychosis, and severe anxiety disorder, respectively. None of the patients had past or family history of psychiatric disease. All three patients had undergone anterior temporal lobectomy on the right side for intractable epilepsy. They remained absolutely seizure-free after surgery. We conclude that psychiatric morbidity may arise de novo long after temporal lobectomy. This association between temporal lobectomy for epilepsy and late onset psychiatric morbidity should be carefully studied. Mechanisms underlying this late complication require deeper understanding of the effects of epilepsy surgery. PMID:27570392

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Does antiepileptic drug withdrawal predispose patients undergoing temporal lobe epilepsy surgery to late onset of psychiatric morbidity? A report of three cases.

    PubMed

    Shukla, Garima; Agarwal, Priya; Sagar, Rajesh; Sood, Mamta; Gupta, Aditya; Suri, Ashish; Garg, Ajay

    2016-01-01

    Surgery is an established and increasingly utilized treatment option in medically refractory temporal lobe epilepsy. Many psychiatric problems are known to complicate in the postoperative period. Most studies have a follow-up period of less than 24 months. We report the cases of three patients who developed severe psychiatric problems in the late postoperative period after successful temporal lobectomy for refractory epilepsy - Psychosis, major depression with psychosis, and severe anxiety disorder, respectively. None of the patients had past or family history of psychiatric disease. All three patients had undergone anterior temporal lobectomy on the right side for intractable epilepsy. They remained absolutely seizure-free after surgery. We conclude that psychiatric morbidity may arise de novo long after temporal lobectomy. This association between temporal lobectomy for epilepsy and late onset psychiatric morbidity should be carefully studied. Mechanisms underlying this late complication require deeper understanding of the effects of epilepsy surgery. PMID:27570392

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

    PubMed

    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.

  20. Drug use and abuse: the ethical issues.

    PubMed

    Almond, B

    1992-01-01

    Drug abuse is both a personal and a public issue, raising questions about individual rights and the boundaries of law, as well as about national sovereignty and international control. Ethical issues that arise under these headings may be related to certain broad ethical positions. The implications of adopting utilitarian assumptions may be contrasted with basing ethics on a theory of individual rights, closely related to a theory of human nature. Neither position justifies a libertarian presumption against control, for, first, an individual decision to expose one's mind and personality to the control of drugs cannot be ethically justified and, second, there are no ethical reasons, nor any compelling arguments from social and political theory, for decriminalizing non-medical drug use. PMID:1638919

  1. Drug Resistance

    MedlinePlus

    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, ...

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

    PubMed

    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.

  3. Drug Abuse

    MedlinePlus

    ... 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 ...

  4. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  5. Fluorescence And Alternative Methods In Urine Drug Testing

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

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

    PubMed

    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

  8. An Update on Drug-induced Liver Injury

    PubMed Central

    Devarbhavi, Harshad

    2012-01-01

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

  9. An Update on Drug-induced Liver Injury.

    PubMed

    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

  10. An Update on Drug-induced Liver Injury.

    PubMed

    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

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

    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

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

    PubMed Central

    Hoffmann, Georg F.

    2016-01-01

    Background Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Methods Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Results Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Conclusion Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation. PMID:27557111

  14. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  15. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing.

  16. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  17. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  18. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  19. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials

    PubMed Central

    Fakheri, Robert; Toklu, Bora; Messerli, Franz H

    2016-01-01

    Objective To evaluate the outcomes with use of renin angiotensin system (RAS) blockers compared with other antihypertensive agents in people with diabetes. Design Meta-analysis. Data sources and study selection PubMed, Embase, and the Cochrane central register of controlled trials databases for randomized trials of RAS blockers versus other antihypertensive agents in people with diabetes mellitus. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, and end stage renal disease. Results The search yielded 19 randomized controlled trials that enrolled 25 414 participants with diabetes for a total of 95 910 patient years of follow-up. When compared with other antihypertensive agents, RAS blockers were associated with a similar risk of death (relative risk 0.99, 95% confidence interval 0.93 to 1.05), cardiovascular death (1.02, 0.83 to 1.24), myocardial infarction (0.87, 0.64 to 1.18), angina pectoris (0.80, 0.58 to 1.11), stroke (1.04, 0.92 to 1.17), heart failure (0.90, 0.76 to 1.07), and revascularization (0.97, 0.77 to 1.22). There was also no difference in the hard renal outcome of end stage renal disease (0.99, 0.78 to 1.28) (power of 94% to show a 23% reduction in end stage renal disease). Conclusions In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and β blockers at reducing the risk of hard cardiovascular and renal endpoints. These findings support the recommendations of the guidelines of the European Society of Cardiology/European Society of Hypertension and eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to also use other antihypertensive agents in people with diabetes but without kidney disease. PMID:26868137

  20. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  1. Rational use of generic psychotropic drugs.

    PubMed

    Carbon, Maren; Correll, Christoph U

    2013-05-01

    For economic reasons, the generic substitution of branded medications is common and welcome. These replacements are based on the concept of bioequivalence, which is considered equal to therapeutic equivalence. Regulatory standards for bioequivalence require the 90 % confidence intervals of group averages of pharmacokinetic measures of a generic and the original drug to overlap within ±20 %. However, therapeutic equivalence has been challenged for several psychotropic agents by retrospective studies and case reports. To evaluate the degree of bioequivalence and therapeutic equivalence of branded and generic psychotropic drugs, we performed an electronic search (from database inception until 24 May 2012 and without language restrictions) in PubMed/MEDLINE, Cochrane Library, and Web of Science. Search terms were "(generic) AND (psychotropic OR psychoactive OR antipsychotic OR antiepileptic OR antidepressant OR stimulant OR benzodiazepine)" or the respective individual substances. We included clinical studies, regardless of design, comparing branded with generic psychotropic drug formulations, identifying 35 such studies. We also included case reports/series reporting on outcomes after a switch between brand and generic psychotropics, identifying 145 clinical cases. Bioequivalence studies in healthy controls or animals, in-vitro studies, and health economics studies without medical information were excluded. An overview of the few randomized controlled studies supports that US FDA regulations assure clinically adequate drug delivery in the majority of patients switched from brand to generic. However, with a growing number of competing generic products for one substance, and growing economic pressure to substitute with the currently cheapest generic, frequent generic-generic switches, often unbeknownst to prescribing clinicians, raise concerns, particularly for antiepileptics/mood stabilizers. Generic-generic switches may vary by more than ±20 % from each other in

  2. Screening for basic drugs in hair of drug addicts by liquid chromatography/time-of-flight mass spectrometry.

    PubMed

    Pelander, Anna; Ristimaa, Johanna; Rasanen, Ilpo; Vuori, Erkki; Ojanperä, Ilkka

    2008-12-01

    Hair analysis in forensic and clinical toxicology has been strongly focused on drugs of abuse, and comprehensive, drug class-independent screening methods based on mass spectrometric detection have not been applied to date. In this study, a qualitative drug screening method by liquid chromatography coupled to time-of-flight mass spectrometry, earlier developed and evaluated for forensic toxicological urine analysis, was adapted for screening of basic drugs in hair. The method included alkaline hydrolysis, purification with mixed-mode solid phase extraction, and analysis by liquid chromatography coupled to time-of-flight mass spectrometry with automated data analysis and reporting. Identification was based on accurate mass, isotopic pattern fit, and retention time, if available. Analysis of 32 hair samples from deceased drug addicts revealed 35 different drugs. The drug classes identified included antidepressants, antipsychotics, antiepileptics, amphetamines, opioids, beta-blockers, a benzodiazepine, a hypnotic, a local anesthetic, an antiemetic, and an antipyretic analgesic. The findings were in good agreement with the findings in blood and urine by other methods. Moreover, information about previous drug use not evident in the analysis of other matrices was obtained in the majority (72%) of the cases. Tramadol was an especially predominant finding, suggesting tramadol abuse as an opioid substitute. One apparent false-positive finding was identified. The mean and median mass accuracies of positive findings were 2.3 and 1.8 ppm, corresponding to 0.5 and 0.4 mDa, respectively. Cutoff values for tramadol and methamphetamine in hair were 100 and 200 pg/mg, respectively. The method proved to be a simple and straightforward tool for comprehensive screening of basic drugs in hair.

  3. COPD - control drugs

    MedlinePlus

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

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

    PubMed

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

    2014-06-01

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

  5. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  6. [Topics from "Overseas Drug Safety Information" in the past five years].

    PubMed

    Amanuma, Kimiko

    2013-01-01

    The Drug Safety Information Section of the Division of Safety Information on Drug, Food and Chemicals has been providing bulletins titled "Overseas Drug Safety Information" in Japanese since 2003. These bulletins comprise summarized and translated reports of important post-marketing drug safety information that are published by foreign regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medical Agency. A new issue of the bulletin is posted every two weeks on the website of the National Institute of Health Sciences, Japan; to date (May 2013), a total of 280 issues have been posted, covering approximately 2400 foreign news items and articles since its inception. Recently, visits to the bulletin website have been increasing: the number of hits for each issue totaled 570,000 in fiscal 2012. Among the "Overseas Drug Safety Information" issued in the past five years, I briefly describe here several topics which interested me: erythropoietin-stimulating agents in chronic kidney disease and their cardiovascular risk; bisphosphonates and atypical femur fracture; effectiveness of oral liquid cough medicines containing codeine in children; bevacizumab for metastatic breast cancer; and congenital abnormality associated with the use of antiepileptic drugs by pregnant women. I also describe the potential safety signals identified by FDA using its Adverse Event Reporting System, and their importance in ensuring the safe use of drugs in the post-marketing phase. PMID:24340668

  7. Drug Resistance in Cortical and Hippocampal Slices from Resected Tissue of Epilepsy Patients: No Significant Impact of P-Glycoprotein and Multidrug Resistance-Associated Proteins

    PubMed Central

    Sandow, Nora; Kim, Simon; Raue, Claudia; Päsler, Dennis; Klaft, Zin-Juan; Antonio, Leandro Leite; Hollnagel, Jan Oliver; Kovacs, Richard; Kann, Oliver; Horn, Peter; Vajkoczy, Peter; Holtkamp, Martin; Meencke, Heinz-Joachim; Cavalheiro, Esper A.; Pragst, Fritz; Gabriel, Siegrun; Lehmann, Thomas-Nicolas; Heinemann, Uwe

    2015-01-01

    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 (CBZ), sodium valproate, phenytoin] and two unspecific inhibitors of Pgp and MRPs [verapamil (VPM) and probenecid (PBN)] on seizure-like events (SLEs) 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 SLEs predominantly persisted in the presence of anticonvulsant drugs (90%) and also in the presence of VPM and PBN (86%). Following subsequent co-administration of anti-epileptic drugs and drug transport inhibitors, SLEs 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 CBZ in PBN 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 do not 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. PMID:25741317

  8. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

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

    PubMed

    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.

  10. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  11. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

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

  12. Accurate Assessment--Compelling Evidence for Practice

    ERIC Educational Resources Information Center

    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…

  13. Telling a Compelling Tale, Scientifically Speaking

    NASA Astrophysics Data System (ADS)

    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.

  14. Chromosome Connections: Compelling Clues to Common Ancestry

    ERIC Educational Resources Information Center

    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…

  15. Energy plight compels ingenuity in Israel

    SciTech Connect

    Bardin, D.J.

    1981-09-01

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

  16. Compelled to do the right thing

    NASA Astrophysics Data System (ADS)

    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.

  17. Prescription and consumption of solid oral drugs dispensed as unitary doses in a third level hospital

    PubMed Central

    Calderón-Guzmán, David; Juárez-Olguín, Hugo; Hernández-García, Ernestina; Medina-Andrade, Alejandro; Juarez Tapia, Belen

    2015-01-01

    Background: The knowledge about the pattern of prescription and consumption of solid oral drugs dispensed as unitary doses (UD) in Mexico is sparing. Purpose: The aim of this study was to describe the pattern of prescription and consumption of solid oral drugs dispensed as unitary doses (UD) in a third level private hospital of Mexico. A retrospective study of a 60-month period (from 2007 to 2011) was carried out to know the pattern of drugs dispensed as UD in a third level hospital. Results: Among the principal drugs consumed were analgesic, antihypertensive, antibiotic, anti-inflammatory, antiepileptic, and diuretics. The dispensation of drugs per year was as follows: 181 drugs with 85,167 UD in 2007; 199 with 90,519 UD in 2008; 193 with 101,479 UD in 2009; 195 with 100,798 UD in 2010; and 198 with 103,913 UD in 2011. Conclusion: The findings confirmed that prescription and consumption of unitary doses in the hospitalization service increased, and revealed the extensive use of analgesics as the principal prescribed drug in this kind of hospital. PMID:27013914

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

    PubMed

    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

  19. Profiling the kinome for drug discovery.

    PubMed

    Yan, S Frank; King, Frederick J; Zhou, Yingyao; Warmuth, Markus; Xia, Gang

    2006-01-01

    The human kinome is made up of 518 distinctive serine/threonine and tyrosine kinases, which are key components of virtually every mammalian signal transduction pathway. Consequently, kinases provide a compelling target family for the development of small molecule inhibitors, which could be used as tools to delineate the mechanism of action for biological processes and potentially be used as therapeutics to treat human diseases such as cancer. A myriad of recent technological advances have accelerated our understanding of kinome function, its relationship to tumorigenic development, and have contributed to the progression of small molecule kinase inhibitors into the clinic. Essential to the continued growth of the field are informatics tools that can assist in interpreting disparate and voluminous data sets and correctly guide decision making processes. These advances are expected to have a dramatic impact on kinase drug development and clinical diagnoses and treatment in the near future.:

  20. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  1. Presence of the HLA-A*3101 allele in a familial case of drug reaction with eosinophilia and systemic symptoms, secondary to carbamazepine.

    PubMed

    Anjum, N; Polak, M E; Ardern-Jones, M; Cooper, H L

    2014-04-01

    Anticonvulsants such as carbamazepine and phenytoin are associated with adverse skin reactions ranging from maculopapular exanthems to more severe reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and toxic epidermal necrolysis. In addition to their antiepileptic role, anticonvulsants are also used to treat pain syndromes including trigeminal neuralgia. Until recently, the associated skin reactions were thought to be unpredictable; however, the current literature suggests a genetic predisposition involving the human leucocyte antigen (HLA) in cutaneous reactions associated with carbamazepine usage. We present two familial cases of DRESS secondary to carbamazepine, in which an underlying genetic predisposition and allelic association were identified.

  2. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  3. Antiretroviral drugs.

    PubMed

    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.

  4. Drug Reactions

    MedlinePlus

    ... or diabetes. But medicines can also cause unwanted reactions. One problem is interactions, which may occur between ... more serious. Drug allergies are another type of reaction. They can be mild or life-threatening. Skin ...

  5. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  6. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  7. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  8. Club Drugs

    MedlinePlus

    ... also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known ...

  9. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  10. Adverse Drug Reactions in Children—A Systematic Review

    PubMed Central

    Smyth, Rebecca Mary Diane; Gargon, Elizabeth; Kirkham, Jamie; Cresswell, Lynne; Golder, Su; Smyth, Rosalind; Williamson, Paula

    2012-01-01

    Background Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided. Methods and Findings We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable. Conclusions There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further

  11. Drug misuse.

    PubMed Central

    Waller, T.

    1992-01-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  12. Multifocal Bullous Fixed Drug Erruption Due To Phenytoin: A Lesson Learned!

    PubMed

    Jain, Ankur; Gupta, Naresh

    2015-12-01

    Antiepileptic drugs (AED) are a common culprit of cutaneous eruptions in clinical practice. Phenytoin, lamotrigine and carbamazepine are the commonest offenders. Maculopapular eruptions are the most frequently reported events. However, multifocal bullous fixed drug eruptions have rarely been described in association with AED use. The risk factors for skin rash including its association with the rate of drug administration are unclear in the literature. We report a case of a young alcoholic man, on long term phenytoin therapy since 3 years, who presented to our emergency department with a breakthrough seizure episode. Patient's routine investigations including serum biochemistry, imaging and toxicology screen were normal. Patient was found to have sub-therapeutic serum phenytoin levels and was prescribed loading with intravenous phenytoin (15mg/kg body weight), which was mistakenly infused at a rapid rate (60mg/minute). Patient developed multifocal bullous lesions over muco-cutaneous regions after 6 hours of drug administration which healed after its discontinuation leaving behind residual hyperpigmentation. Patient was managed conservatively, switched to oral levetiracetam and discharged in a stable condition after one week of hospital stay. Present case highlights a yet uncommon reaction to a commonly used drug and tries to establish the relation between rate of drug infusion and the risk of skin reaction. PMID:26816935

  13. Design of HIV Protease Inhibitors Targeting Protein Backbone: An Effective Strategy for Combating Drug Resistance

    SciTech Connect

    Ghosh, Arun K.; Chapsal, Bruno D.; Weber, Irene T.; Mitsuya, Hiroaki

    2008-06-03

    The discovery of human immunodeficiency virus (HIV) protease inhibitors (PIs) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance.

  14. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided.

  15. Drug Allergy.

    PubMed

    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

  16. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.

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

    PubMed

    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

  18. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    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…

  19. Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase

    PubMed Central

    Ferrajolo, Carmen; Capuano, Annalisa; Verhamme, Katia M C; Schuemie, Martijn; Rossi, Francesco; Stricker, Bruno H; Sturkenboom, Miriam C J M

    2010-01-01

    AIM To identify which drugs are associated with reports of suspected hepatic injury in children and adolescents. METHODS Using a worldwide pharmacovigilance database, VigiBase, we conducted a case/non-case study on suspected adverse drug reactions (ADRs) occurring in the population <18 years old. Cases were all the records with hepatic ADRs and non-cases were all the other ADR records. Records regarding topically administered drugs were excluded from both groups. The association between drug and suspected hepatic ADRs was calculated using the reporting odds ratio (ROR) as a measure of disproportionality while adjusting for gender, country, reporter and calendar year. Sub-analyses were performed within therapeutic class and by excluding vaccination-related reports to reduce confounding. RESULTS Overall, 6595 (1%) out of 624 673 ADR records in children and adolescents concerned hepatic injury. Most of the reported hepatic injuries concerned children 12–17 years of age. Drugs that were most frequently reported as suspected cause and were associated with hepatic injury comprised paracetamol, valproic acid, carbamazepine, methotrexate, minocycline, zidovudine, pemoline, ceftriaxone, bosentan, ciclosporin, atomoxetine, olanzapine, basiliximab, erythromycin and voriconazole. The association between hepatotoxicity and all these drugs, except for basiliximab, is already known. CONCLUSIONS Drug-induced hepatic injury is infrequently reported (only 1% of total) as a suspected ADR in children and adolescents. The drugs associated with reported hepatotoxicity (paracetamol, antiepileptic and anti-tuberculosis agents) are known to be hepatotoxic in adults as well, but age related changes in associations were observed. VigiBase is useful as a start to plan further drug safety studies in children. PMID:21039766

  20. AEDs and psychotropic drugs in children with autism and epilepsy.

    PubMed

    Tuchman, Roberto

    2004-01-01

    The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.

  1. Hair testing in clinical setting: Simultaneous determination of 50 psychoactive drugs and metabolites in headache patients by LC tandem MS.

    PubMed

    Licata, Manuela; Rustichelli, Cecilia; Palazzoli, Federica; Ferrari, Anna; Baraldi, Carlo; Vandelli, Daniele; Verri, Patrizia; Marchesi, Filippo; Silingardi, Enrico

    2016-07-15

    Headache patients suffering from recurrent attacks are a population at risk of overuse and abuse of analgesic medications. Associated with triptans, the first-line drugs recommended for the acute treatment, these patients usually take other medications such as opioids analgesics for the attack treatment, antidepressants and antiepileptics for prophylaxis treatment and benzodiazepines, non-benzodiazepine hypnotics and antipsychotics for the treatment of comorbidities. Regular and frequent use of triptans, like of any other symptomatic analgesic, can cause chronic headache and medication-overuse headache (MOH). In these circumstances, a detoxification treatment is necessary and therefore the monitoring and follow-up of the patients are crucial to the success of the treatment. In the present study, a LC tandem MS method has been developed for the identification of 50 psychoactive drugs in human hair, including triptans, benzodiazepines and metabolites, analgesics, antiepileptic, antidepressants and metabolites, a non-benzodiazepine hypnotic (z-drug), antipsychotics and metabolites. Hair samples were decontaminated, pulverized and incubated overnight in methanol; the extracts were then purified by a new and rapid QuEChERS procedure and analyzed by LC-MS/MS under gradient elution with positive ionization MRM mode. The procedure was fully validated in terms of selectivity, linearity, limit of detection and lower limit of quantitation, precision and accuracy, carry-over, matrix effect, recovery and dilution integrity. The validated procedure has been applied to 234 real hair samples collected from headache patients with known type and dosage of the taken drugs; the obtained data could be of interest to evaluate the xenobiotic concentrations in patients with known therapy. PMID:27136283

  2. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

  3. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

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

    PubMed

    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 (P<0.001). The definition appeared to have a high degree of interrater reliability in this setting.

  5. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.

  6. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... 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 ...

  7. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  8. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  9. Open Challenges in Magnetic Drug Targeting

    PubMed Central

    Kulkarni, Sandip; Nacev, Aleksander; Muro, Silvia; Stepanov, Pavel Y.; Weinberg, Irving N.

    2014-01-01

    The principle of magnetic drug targeting, wherein therapy is attached to magnetically responsive carriers and magnetic fields are used to direct that therapy to disease locations, has been around for nearly two decades. Yet our ability to safely and effectively direct therapy to where it needs to go, for instance to deep tissue targets, remains limited. To date, magnetic targeting methods have not yet passed regulatory approval or reached clinical use. Below we outline key challenges to magnetic targeting, which include designing and selecting magnetic carriers for specific clinical indications, safely and effectively reaching targets behind tissue and anatomical barriers, real-time carrier imaging, and magnet design and control for deep and precise targeting. Addressing these challenges will require interactions across disciplines. Nanofabricators and chemists should work with biologists, mathematicians and engineers to better understand how carriers move through live tissues and how to optimize carrier and magnet designs to better direct therapy to disease targets. Clinicians should be involved early on and throughout the whole process to ensure the methods that are being developed meet a compelling clinical need and will be practical in a clinical setting. Our hope is that highlighting these challenges will help researchers translate magnetic drug targeting from a novel concept to a clinically-available treatment that can put therapy where it needs to go in human patients. PMID:25377422

  10. Drugs Approved for Neuroblastoma

    Cancer.gov

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

  11. Drugs Approved for Retinoblastoma

    Cancer.gov

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

  12. Drugs Approved for Leukemia

    Cancer.gov

    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. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  14. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  15. [Drug poisoning].

    PubMed

    Gainza, I; Nogué, S; Martínez Velasco, C; Hoffman, R S; Burillo-Putze, G; Dueñas, A; Gómez, J; Pinillos, M A

    2003-01-01

    A review is made of acute poisoning by opiates and its treatment in the emergency services, bearing in mind the progressive decline in the number of cases presented with the arrival of new forms of their administration, as well as the presence of new addictive drugs that have resulted in a shift in consumption habits. Reference is also made to the way in which the different types of existing substances originated, with the aim of achieving a better understanding of their use and in order to administer the most suitable treatment when poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical picture, diagnosis and treatment. The consumption of illegal drugs in our country has undergone a notable change in recent years, with heroin being relegated and the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA), "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of cannabis and its derivates, from the history of its consumption and the preparations employed to the effects produced in the different bodily systems. A brief explanation is also given of its metabolites and its principal mechanisms of action. Finally, we comment on the effects of LSD and hallucinogenic mushrooms.

  16. Drugs and the Brain.

    ERIC Educational Resources Information Center

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

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

  17. On the Slow Diffusion of Point-of-Care Systems in Therapeutic Drug Monitoring

    PubMed Central

    Sanavio, Barbara; Krol, Silke

    2015-01-01

    Recent advancements in point-of-care (PoC) technologies show great transformative promises for personalized preventative and predictive medicine. However, fields like therapeutic drug monitoring (TDM), that first allowed for personalized treatment of patients’ disease, still lag behind in the widespread application of PoC devices for monitoring of patients. Surprisingly, very few applications in commonly monitored drugs, such as anti-epileptics, are paving the way for a 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 over-viewing both TDM 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. PMID:25767794

  18. Circular dichroism and synchrotron radiation circular dichroism spectroscopy: tools for drug discovery.

    PubMed

    Wallace, B A; Janes, Robert W; Wallace, Bonnie A

    2003-06-01

    CD spectroscopy is an established and valuable technique for examining protein structure, dynamics and folding. Because of its ability to sensitively detect conformational changes, it has important potential for drug discovery, enabling screening for ligand and drug binding, and detection of potential candidates for new pharmaceuticals. The binding of the anti-tumour agent Taxol to the anti-apoptosis protein Bcl-2 [Rodi, Janes, Sanganee, Holton, Wallace and Makowski (1999) J. Mol. Biol. 285, 197-204] and the binding of the anti-epileptic drug lamotrigine to voltage-gated sodium channels [Cronin, O'Reilly, Duclohier and Wallace (2003) J. Biol. Chem. 278, 10675-10682] are used as examples to show changes detectable by CD involving secondary structure, and are contrasted with the binding of the agonist carbamylcholine to acetylcholine receptors [Mielke and Wallace (1988) J. Biol. Chem. 263, 8177-8182], an example where binding does not involve a secondary structural change. Synchrotron radiation CD spectroscopy offers significant enhancements with respect to conventional CD spectroscopy, which will enable its usage for high-throughput screening and as a tool in 'chemical genomics' or 'reverse chemical genetics' strategies for ligand identification. The lower wavelength data available enable more detailed, sensitive and accurate detection, the higher light intensity permits much smaller amounts of both proteins and drug candidates to be used in the screening, and future technological developments in sample handling and detection should enable automated high-throughput screening to be performed.

  19. Finding a better drug for epilepsy: Preclinical screening strategies and experimental trial design

    PubMed Central

    Simonato, Michele; Löscher, Wolfgang; Cole, Andrew J.; Dudek, F. Edward; Engel, Jerome; Kaminski, Rafal M.; Loeb, Jeffrey A.; Scharfman, Helen; Staley, Kevin J.; Velíšek, Libor; Klitgaard, Henrik

    2014-01-01

    SUMMARY The antiepileptic drugs (AEDs) introduced during the past two decades have provided several benefits: they offered new treatment options for symptomatic treatment of seizures, improved ease of use and tolerability, and lowered risk for hypersensitivity reactions and detrimental drug– drug interactions. These drugs, however, neither attenuated the problem of drug-refractory epilepsy nor proved capable of preventing or curing the disease. Therefore, new preclinical screening strategies are needed to identify AEDs that target these unmet medical needs. New therapies may derive from novel targets identified on the basis of existing hypotheses for drug-refractory epilepsy and the biology of epileptogenesis; from research on genetics, transcriptomics, and epigenetics; and from mechanisms relevant for other therapy areas. Novel targets should be explored using new preclinical screening strategies, and new technologies should be used to develop medium- to high-throughput screening models. In vivo testing of novel drugs should be performed in models mimicking relevant aspects of drug refractory epilepsy and/or epileptogenesis. To minimize the high attrition rate associated with drug development, which arises mainly from a failure to demonstrate sufficient clinical efficacy of new treatments, it is important to define integrated strategies for preclinical screening and experimental trial design. An important tool will be the discovery and implementation of relevant biomarkers that will facilitate a continuum of proof-of-concept approaches during early clinical testing to rapidly confirm or reject preclinical findings, and thereby lower the risk of the overall development effort. In this review, we overview some of the issues related to these topics and provide examples of new approaches that we hope will be more successful than those used in the past. PMID:22708847

  20. Perampanel: A Review in Drug-Resistant Epilepsy.

    PubMed

    Frampton, James E

    2015-09-01

    Perampanel (Fycompa®), an orally-active, selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is a first-in-class antiepileptic drug (AED) offering the convenience of once-daily administration. In the EU and US, perampanel is approved in patients with epilepsy aged ≥12 years for the adjunctive treatment of primary generalized tonic-clonic seizures (GTCS) and partial-onset seizures (POS; with or without secondary generalization). In phase III trials of 17 or 19 weeks' duration, add-on perampanel ≤12 mg/day significantly improved seizure control in patients aged ≥12 years who were experiencing either primary GTCS or POS (with or without secondary generalization), despite ongoing treatment with stable dosages of one to three AEDs. Improvements in seizure control were maintained for up to 2 years in extensions of these core studies. Perampanel also provided sustained seizure control for up to ≈4 years in an extension of two phase II studies in patients aged ≥18 years with drug-resistant POS. Adjunctive perampanel therapy was generally well tolerated. Treatment-emergent adverse events were most commonly CNS-related (e.g. dizziness, somnolence, fatigue and irritability) and dose-related; however, most were of mild to moderate intensity. Clinical experience with perampanel is accumulating, although comparative studies and pharmacoeconomic data that could assist in positioning it relative to other AEDS that are approved and/or recommended as adjunctive therapy are lacking. Nonetheless, on the basis of its overall clinical profile and unique mechanism of action, perampanel is a useful additional adjunctive treatment option for patients with drug-resistant POS, with or without secondary generalization, and primary GTCS. PMID:26370209

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

    PubMed

    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.

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

    PubMed

    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.

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

    ERIC Educational Resources Information Center

    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)…

  4. Drug-drug interaction between oxycodone and adjuvant analgesics in blood-brain barrier transport and antinociceptive effect.

    PubMed

    Nakazawa, Yusuke; Okura, Takashi; Shimomura, Keita; Terasaki, Tetsuya; Deguchi, Yoshiharu

    2010-01-01

    To examine possible blood-brain barrier (BBB) transport interactions between oxycodone and adjuvant analgesics, we firstly screened various candidates in vitro using [(3)H]pyrilamine, a substrate of the oxycodone transporter, as a probe drug. The uptake of [(3)H]pyrilamine by conditionally immortalized rat brain capillary endothelial cells (TR-BBB13) was inhibited by antidepressants (amitriptyline, imipramine, clomipramine, amoxapine, and fluvoxamine), antiarrhythmics (mexiletine, lidocaine, and flecainide), and ketamine. On the other hand, antiepileptics (carbamazepine, phenytoin, and clonazepam) and corticosteroids (dexamethasone and prednisolone) did not inhibit [(3)H]pyrilamine uptake, with the exception of sodium valproate. The uptake of oxycodone was significantly inhibited in a concentration-dependent manner by amitriptyline, fluvoxamine and mexiletine with K(i) values of 13, 65, and 44 microM, respectively. These K(i) values are 5-300 times greater than the human therapeutic plasma concentrations. Finally, we evaluated in vivo interaction between oxycodone and amitriptyline in mice. Antinociceptive effects of oxycodone were increased by coadministration of amitriptyline. The oxycodone concentrations in plasma and brain were not changed by coadministration of amitriptyline. Overall, the results suggest that several adjuvant analgesics may interact with the BBB transport of oxycodone at relatively high concentrations. However, it is unlikely that there would be any significant interaction at therapeutically or pharmacologically relevant concentrations. PMID:19499573

  5. Accelerating the paradigm shift toward inclusion of pregnant women in drug research: Ethical and regulatory considerations.

    PubMed

    White, Amina

    2015-11-01

    Although there has been long-standing reluctance to include pregnant women as clinical trial participants, increasing recognition of profound gaps in research on the safety and efficacy of drugs often prescribed to pregnant women calls into question the practice of routinely excluding them. This article presents compelling reasons for including pregnant women in clinical research, highlights certain regulatory barriers to the inclusion of pregnant women, and proposes that professional societies with expertise in obstetrics and maternal-fetal medicine can be instrumental in hastening the paradigm shift from the systematic exclusion of pregnant women in research to a one of responsible and fair inclusion. PMID:26385413

  6. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  7. Rufinamide efficacy and safety as adjunctive treatment in children with focal drug resistant epilepsy: the first Italian prospective study.

    PubMed

    Moavero, Romina; Cusmai, Raffaella; Specchio, Nicola; Fusco, Lucia; Capuano, Alessandro; Curatolo, Paolo; Vigevano, Federico

    2012-11-01

    Rufinamide is a new antiepileptic drug approved as add-on treatment in Lennox-Gastaut syndrome from the age of 4 years, and for the treatment of focal seizures in adults and adolescents. The aim of this prospective study was to evaluate the safety and efficacy of add-on Rufinamide in the treatment of childhood focal drug resistant epilepsy. We recruited 70 patients for a prospective, add-on, open-label study. Inclusion criteria were: 3 years of age or more; focal drug resistant epilepsy despite the use of three previous AEDs; use of at least one other AED, but no more than three at baseline; more than one seizure per month in the previous 6 months. Rufinamide efficacy was observed up to 12 months of follow-up, with a total responder rate of 38.57%. We found the best results in focal epilepsies due to structural/metabolic etiology (42.6%). The responder rate was similar for focal seizures with secondary generalization, simple focal seizures other than myoclonic jerks, and complex partial seizures. Response to Rufinamide was not related to the age. Our experience suggests that Rufinamide can be effective in reducing focal seizure frequency in children with drug resistant epilepsy, and that it can be considered as a safe drug. PMID:22677424

  8. Optimizing early Go/No Go decisions in CNS drug development.

    PubMed

    Potter, William Z

    2015-03-01

    Go/No Go decisions concerning development of any single compound determine investment in increasingly costly studies from Phases I-III. Such decisions are problematic for CNS drug development where the variety of molecular targets in the brain have stimulated decades of studies without major therapeutic advances. Many costly studies do not even yield interpretable results as to whether the mechanism being pursued has therapeutic potential. Therefore, both industry and the public sector have implemented a decision making strategy based on whether a compound can test a molecular hypothesis of drug action. One requires, at a minimum, compelling evidence in humans that a compound both interacts with its presumed molecular targets in brain and ideally documents a CNS functional consequence of the interaction prior to efficacy studies. This strategy will much more quickly rule out ineffective mechanisms although it does not address the problem of poorly predictive models of novel CNS drug efficacy.

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

    PubMed

    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.

  10. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  11. Attitudes towards drug legalization among drug users.

    PubMed

    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.

  12. Drug Use by Students of Drug Abuse

    ERIC Educational Resources Information Center

    Linder, Ronald; And Others

    1973-01-01

    The purpose of this study was to determine the significance of differences in the use of certain psychoactive drugs among students who enrolled for an elective drug abuse course and students not enrolled, or who have not previously taken a drug abuse course. (Author)

  13. Discontinued drugs in 2008: cardiovascular drugs.

    PubMed

    Zhang, Xu-Song; Xiang, Bing-Ren

    2009-07-01

    This perspective is part of an annual series of papers discussing drugs dropped from clinical development in the previous year. Specifically, this paper focuses on the 16 cardiovascular drugs discontinued in 2008. Information for this perspective was derived from a search of the Pharmaprojects database for drugs discontinued after reaching Phase I-III clinical trials. PMID:19548849

  14. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  15. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  16. Drugs Approved for Leukemia

    MedlinePlus

    ... 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. Drug Retention Times

    SciTech Connect

    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.

  18. Drug Retention Times

    SciTech Connect

    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-induced hepatitis

    MedlinePlus

    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 ...

  20. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  1. [Drug-induced dementia].

    PubMed

    Kojima, Taro; Akishita, Masahiro

    2016-03-01

    Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function. PMID:27025096

  2. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  3. Registries Help Moms Measure Medication Risks

    MedlinePlus

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

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

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    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 models and

  5. Drug-induced Depression: a Case/Non Case Study in the French Pharmacovigilance Database.

    PubMed

    Lafay-Chebassier, Claire; Chavant, François; Favrelière, Sylvie; Pizzoglio, Véronique; Pérault-Pochat, Marie-Christine

    2015-01-01

    Depression is a complex disorder with heterogeneous clinical anomalies whose neurobiological understanding still remains unclear. Medications have been implicated as potential causes of depression but for many of them, data are controversial. The present study aims to investigate association bet ween drugs and reports of depression. We used the case/non case method in the French pharmacovigilance database (FPVD) to identify drugs associated with depression. Cases were reports of depression in the FPVD between January 2007 and December 2011. Non cases were all other reports during the same period. Data were expressed as reporting odds ratio (ROR) with their 95% confidence interval. Of the 114,692 reports recorded in the FPVD during the studied period, we identified 474 cases of depression. For the majority of the patients, they were considered as "non serious" (56%) and evolution was favorable (64%). Significant RORs were found for antiepileptics (topiramate, levetiracetam), anti-infective and especially anti-retroviral drugs (efavirenz, emtricitabine, tenofovir, etravirine, raltegravir), interferons and other agents including isotretinoin, methylphenidate, sodium oxybate, varenicline, montelukast, flunarizine, adalimumab, anastrozole. Taking into account the limits of the methodology, the present study described associations with mainly expected drugs belonging to various therapeutic classes but it also found a signal with some anti-retrovirals. On the contrary, we did not find some assumed associations like cardiovascular medications, antimalarial. For most of the drugs, one or more mechanisms were found to explain these depressogenic effects on the basis of animal and human literature. Even if such associations need to be confirmed by further prospective studies, cautions are necessary for many drugs to early detect depressive symptoms. PMID:26056040

  6. Managing drug-resistant epilepsy: challenges and solutions

    PubMed Central

    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

  7. Exposure to rufinamide and risks of CNS adverse events in drug-resistant epilepsy: a meta-analysis of randomized, placebo-controlled trials

    PubMed Central

    Alsaad, Abdulaziz M S; Koren, Gideon

    2014-01-01

    Aim Epilepsy is a complex disease necessitating continuous development of new therapeutic strategies to encounter drug-resistant cases. Among new adjuvant antiepileptic drugs, rufinamide is structurally distinct from other antiepileptic drugs. It is used to treat partial-onset seizures and seizures associated with Lennox-Gastaut syndrome (LGS) in adult and children. To date, there has been no attempt to evaluate systematically the risks of adverse events with rufinamide. Methods We performed a quantitative risk analysis of central nervous system (CNS) adverse events of rufinamide from all randomized, double-blind, add-on, placebo-controlled trials. The meta-analysis was undertaken with fixed effects models. Results Of the 886 publications reviewed, 99 papers were retrieved and five articles met the inclusion criteria. One thousand two hundred and fifty-two patients were included. Our study showed that exposure to rufinamide was associated with a significant increase in risk of somnolence [relative ratio (RR) 1.87; 95% confidence interval (CI) 1.33, 2.62; P = 0.0003], dizziness (RR 2.66; 95% CI 2.00, 3.55; P = 0.00001), fatigue (RR 2.14; 95% CI 1.57, 2.91; P = 0.01) and headache (RR 1.28; 95% CI 1.02, 1.59, P = 0.03). In addition, exposure to rufinamide was associated with higher treatment discontinuation rates as compared with placebo (RR 2.65; 95% CI 1.74, 4.03; P = 0.00001). Conclusions The risk of CNS adverse events appears to be increased in patients exposed to rufinamide as well as the treatment discontinuation rates. However, although statistical associations were significant, additional long term safety studies are required to confirm the clinical significance of these findings, as most reports described only mild and moderate adverse events. PMID:25132372

  8. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  9. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  10. Drugs and Young People

    MedlinePlus

    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 ...

  11. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

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

    PubMed Central

    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

  13. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  14. Facile synthesis of new imidazo[1,2-a]pyridines carrying 1,2,3-triazoles via click chemistry and their antiepileptic studies.

    PubMed

    Ulloora, Shrikanth; Shabaraya, Ramakrishna; Adhikari, Airody Vasudeva

    2013-06-01

    The present article reports the synthesis and anticonvulsant studies of new 2-arylimidazo[1,2-a]pyridines carrying suitably substituted 1,2,3-triazoles as well as their intermediates. The structures of newly synthesized compounds were confirmed by various spectroscopic techniques. The anticonvulsant study was carried out by MES and scPTZ screening methods, while their toxicity study was performed following Rotarod method. The active compounds showed enhanced seizure control in scPTZ method when compared with that of MES method. Compounds 3f, 4c, 4f, 5k, 5p and 5w carrying active pharmacophores exhibited complete protection against seizure and their results were comparable with standard drug diazepam. Majority of new compounds were found to be non-toxic, while few of them showed toxicity at 100 mg/kg. The clogP values of target compounds are in the range of 3.5-5.3, which confirm their lipophilic nature.

  15. Analgesic drug use and risk of epithelial ovarian cancer.

    PubMed

    Hannibal, Charlotte G; Rossing, Mary Anne; Wicklund, Kristine G; Cushing-Haugen, Kara L

    2008-06-15

    Analgesic use may reduce ovarian cancer risk, possibly through antiinflammatory or antigonadotropic effects. The authors conducted a population-based, case-control study in Washington State that included 812 women aged 35-74 years who were diagnosed with epithelial ovarian cancer between 2002 and 2005 and 1,313 controls. Use of analgesics, excluding use within the previous year, was assessed via in-person interviews. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Overall, acetaminophen and aspirin were associated with weakly increased risks of ovarian cancer. These associations were stronger after more than 10 years of use (acetaminophen: odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.6; aspirin: OR = 1.6, 95% CI: 1.1, 2.2) and were present for indications of headache, menstrual pain, and other pain/injury. Reduced risk was observed among aspirin users who began regular use within the previous 5 years (OR = 0.6, 95% CI: 0.4, 1.0) or used this drug for prevention of heart disease (OR = 0.7, 95% CI: 0.5, 1.0). These results, in the context of prior findings, do not provide compelling evidence of a true increase in risk of ovarian cancer among women who use these drugs. However, they add to the weight of evidence that, in the aggregate, provides little support for the use of analgesic drugs as chemoprevention for this disease.

  16. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  17. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  18. Therapy against organophosphate poisoning: The importance of anticholinergic drugs with antiglutamatergic properties

    SciTech Connect

    Weissman, Ben Avi Raveh, Lily

    2008-10-15

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission.

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

    PubMed Central

    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

  20. A critical test of the hippocampal theta model of anxiolytic drug action.

    PubMed

    Yeung, Michelle; Treit, Dallas; Dickson, Clayton T

    2012-01-01

    Hippocampal theta rhythms have been associated with a number of behavioural processes, including learning, memory and arousal. Recently it has been argued that the suppression of hippocampal theta is a valid indicator of anxiolytic drug action. Like all such models, however, it has relied almost exclusively on the experimental effects of well-known, clinically proven anxiolytic compounds for validation. The actual predictive validity of putative models of anxiolytic drug action, however, cannot be rigorously tested with this approach alone. The present study provides a stringent test of the predictive validity of the theta suppression model, using the drug phenytoin (50 mg/kg and 10 mg/kg), and a positive comparison compound, diazepam (2 mg/kg). Phenytoin has two important properties that are advantageous for assessing the validity of the theta suppression model: 1) it is a standard antiepileptic drug with no known anxiolytic effects, and 2) its primary mechanism of action is through suppression of the persistent sodium current, an effect that should also suppress hippocampal theta. Because of the latter property, we also directly compared the effects of phenytoin in the theta suppression model with its effects in the most widely tested behavioural model of anxiolytic drug action, the elevated plus-maze. While an anxiolytic-like effect of phenytoin in the theta suppression model might be expected simply due to its suppressive effects on sodium channel currents, anxiolytic effects in both tests would provide strong support for the predictive validity of the theta suppression model. Surprisingly, phenytoin produced clear anxiolytic-like effects in both neurophysiological and behavioural models, thus providing strong evidence of the predictive validity of the theta suppression model. This article is part of a Special Issue entitled 'Anxiety and Depression'.

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

    PubMed

    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.

  2. Do drug offences matter?

    PubMed

    Gordon, A M

    1978-07-15

    Drug offences in addicts are often thought to indicate little more than continued dependency. In a four-year follow-up study of 60 men attending a drug clinic a history of repeated convictions for drug offences was found to be strongly related to patterns of delinquency. The following variables were associated with a history of repeated drug offences: a higher conviction rate for "non-drug" offences; younger age at first conviction; conviction preceding drug use; convictions for offences of sex and violence; longer prison sentences; and regular narcotic use and continued dependency at follow-up. Receiving a clinic prescription was not associated with a lower incidence of drug offences. Repeated drug offences identified a subgroup of drug users who were characterised by extensive sociopathic behaviour. Such offences should not be dismissed as an unavoidable, unimportant part of addiction. PMID:678840

  3. Modulation of Immunity and the Inflammatory Response: A New Target for Treating Drug-resistant Epilepsy

    PubMed Central

    Yu, Nian; Liu, Hao; Di, Qing

    2013-01-01

    Until recently, epilepsy medical therapy is usually limited to anti-epileptic drugs (AEDs). However, approximately 1/3 of epilepsy patients, described as drug-resistant epilepsy (DRE) patients, still suffer from continuous frequent seizures despite receiving adequate AEDs treatment of sufficient duration. More recently, with the remarkable progress of immunology, immunity and inflammation are considered to be key elements of the pathobiology of epilepsy. Activation of inflammatory processes in brain tissue has been observed in both experimental seizure animal models and epilepsy patients. Anti-inflammatory and immunotherapies also showed significant anticonvulsant properties both in clinical and in experimental settings. The above emerging evidence indicates that modulation of immunity and inflammatory processes could serve as novel specific targets to achieve potential anticonvulsant effects for the patients with epilepsy, especially DRE. Herein we review the recent evidence supporting the role of inflammation in the development and perpetuation of seizures, and also discuss the recent achievements in modulation of inflammation and immunotherapy applied to the treatment of epilepsy. Apart from medical therapy, we also discuss the influences of surgery, ketogenic diet, and electroconvulsive therapy on immunity and inflammation in DRE patients. Taken together, a promising perspective is suggested for future immunomodulatory therapies in the treatment of patients with DRE. PMID:23814544

  4. A population-based study of active and drug-resistant epilepsies in Northern Italy.

    PubMed

    Giussani, Giorgia; Canelli, Valentina; Bianchi, Elisa; Franchi, Carlotta; Nobili, Alessandro; Erba, Giuseppe; Beghi, Ettore

    2016-02-01

    Drug-resistant epilepsy (DRE) is defined by the International League Against Epilepsy as a failure of adequate trials of two tolerated, appropriately chosen, and used antiepileptic drugs to achieve sustained seizure freedom. Our aim was to calculate the following: (1) the prevalence of active epilepsy and DRE in a well-defined population of Northern Italy and (2) the proportion of incident cases developing DRE. The study population (146,506; year 2008) resided in the province of Lecco, Northern Italy. The medical records of 123 general practitioners were reviewed to identify patients with epilepsy, diagnosed by a neurologist during the period 2000-2008. The point prevalence of active epilepsy and DRE was calculated on December 31, 2008. A total of 747 prevalent patients with epilepsy, 684 patients with active epilepsy, and 342 incident cases were identified. The frequency of DRE was 15.6% (107/684) of all active epilepsies and 10.5% (36/342) of incident cases. The point prevalence was 0.73 per 1000. The standardized prevalence of DRE was 0.7 per 1000 (Italian population) and 0.8 per 1000 (world population). Our data indicate that 1/6 patients with active epilepsy in the general population has DRE, and 1/10 patients with newly diagnosed epilepsy will develop DRE within nine years from the diagnosis.

  5. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  6. Discontinued drugs in 2010: cardiovascular drugs.

    PubMed

    Zhao, Hong-ping; Zhang, Xu-song; Xiang, Bing-ren

    2011-10-01

    This perspective is a paper discussing drugs dropped from clinical development in the previous years. Specifically, this paper focuses on 16 cardiovascular drugs discontinued in 2010 after reaching Phase I - III clinical trials. Information for this perspective is mainly derived from a search of Pharmaprojects. PMID:21870899

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

    PubMed

    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

  8. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations

    PubMed Central

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG), a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB), which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+) bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT) littermates, at 63–100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg) were recorded using a video-electroencephalography (EEG) monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine’s scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations. PMID:26910900

  9. Factors affecting the determination of drugs and endogenous low molecular mass compounds in human serum by micellar electrokinetic capillary chromatography with direct sample injection.

    PubMed

    Schmutz, A; Thormann, W

    1994-01-01

    Factors influencing the establishment of an analytical window in front of the solubilized proteins in micellar electrokinetic capillary chromatography (MECC) with direct serum injection (DSI) are discussed. Both drugs and endogenous low molecular mass compounds eluting within the analytical window are identified concurrently by multi-wavelength absorption detection. Variables such as the concentration of the micelle forming substance, ionic strength, applied voltage, initial sample zone length, capillary length, selected buffer additives, insufficient renewal of the buffer in the anodic buffer vial and sample matrix are shown to impact MECC of endogenous compounds and model drugs, such as antiepileptics. For two drugs eluting within the analytical window, phenobarbital and ethosuximide, serum levels determined by DSI with external calibration are shown to compare well with levels obtained after liquid-liquid extraction and internal calibration (use of an internal standard). In addition, reproducibility of both assays is excellent. The limit of employing DSI is demonstrated with the determination of the hydrophobic drug phenytoin. Using an automated, commercial instrument and naproxen as model drug, high-speed MECC separations of high reproducibility and with a throughput of 12-15 samples per h are presented.

  10. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices.

  11. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  12. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  13. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  14. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  15. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  16. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  17. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  18. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  19. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  20. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...