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Special Issue "Antiepileptic Drugs"

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A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 April 2010)

Special Issue Editor

Guest Editor
Prof. Dr. Sandra L. Helmers

Department of Neurology/Epilepsy, The Emory Clinic, 1365-A Clifton Road, NE, Suite A3400, Atlanta, GA 30322, USA
Interests: treatment of pediatric and adult epilepsy; anticonvulsants in the treatment of epilepsy; quality indicators in epilepsy care; economic analysis of epilepsy treatments

Special Issue Information

Dear Colleagues,

This special issue will address the pharmacologic treatment of epilepy and seizures. We will explore current understandings of mechanism of actions of anticonvulsants, efficacy and side effect profiles of currently available anticonvulsants, and look at the anticonvulsant "pipeline".

Prof. Dr. Sandra L. Helmers
Guest Editor

Keywords

  • anticonvulsant medications
  • mechanism of action
  • epilepsy
  • seizures
  • anticonvulsant pharmacology
  • drug interactions
  • anticonvulsant side effects
  • anticonvulsant efficacy
  • economic analysis

Published Papers (7 papers)

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Review

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Open AccessReview The Art of Managing Conversions between Antiepileptic Drugs: Maximizing Patient Tolerability and Quality of Life
Pharmaceuticals 2010, 3(9), 2956-2969; doi:10.3390/ph3092956
Received: 29 July 2010 / Revised: 12 August 2010 / Accepted: 2 September 2010 / Published: 6 September 2010
Cited by 8 | PDF Full-text (128 KB) | HTML Full-text | XML Full-text
Abstract
Conversion between anti-epilectic drugs (AEDs) is frequently necessary in epilepsy care, exposing patients to a risk of incurring adverse effects and reduced quality of life. Little practical guidance is available to practitioners to guide conversions between AED monotherapies, or in adding a [...] Read more.
Conversion between anti-epilectic drugs (AEDs) is frequently necessary in epilepsy care, exposing patients to a risk of incurring adverse effects and reduced quality of life. Little practical guidance is available to practitioners to guide conversions between AED monotherapies, or in adding a new adjunctive AED into a polytherapy regimen. This article reviews the impact of adverse effects of AEDs on quality of life in epilepsy patients, then reviews several important patient-related factors such as age, gender, medical and psychiatric co-morbidities, and co-medications that must be considered when selecting AEDs and ensuring tolerable and safe AED conversions. Practical strategies for transitional polytherapy AED conversion are then considered in different commonly encountered clinical scenarios in newly diagnosed and refractory epilepsy care, including inadequate seizure control, intolerable adverse effects, or idiosyncratic safety hazards. Successful conversion between AEDs requires regular monitoring for patient-reported adverse effects and appropriately reactive adjustment of AED therapy to maximize patient quality of life. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
Open AccessReview Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy
Pharmaceuticals 2010, 3(8), 2709-2732; doi:10.3390/ph3082709
Received: 31 May 2010 / Revised: 10 August 2010 / Accepted: 17 August 2010 / Published: 20 August 2010
Cited by 5 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome [...] Read more.
Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs). However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP) 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
Open AccessReview Rational Polytherapy with Antiepileptic Drugs
Pharmaceuticals 2010, 3(8), 2362-2379; doi:10.3390/ph3082362
Received: 30 June 2010 / Revised: 21 July 2010 / Accepted: 22 July 2010 / Published: 26 July 2010
Cited by 5 | PDF Full-text (154 KB) | HTML Full-text | XML Full-text
Abstract
Approximately 30–40% of patients do not achieve seizure control with a single antiepileptic drug (AED). With the advent of multiple AEDs in the past 15 years, rational polytherapy, the goal of finding combinations of AEDs that have favorable characteristics, has become of [...] Read more.
Approximately 30–40% of patients do not achieve seizure control with a single antiepileptic drug (AED). With the advent of multiple AEDs in the past 15 years, rational polytherapy, the goal of finding combinations of AEDs that have favorable characteristics, has become of greater importance. We review the theoretical considerations based on AED mechanism of action, animal models, human studies in this field, and the challenges in finding such optimal combinations. Several case scenarios are presented, illustrating examples of rational polytherapy. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
Open AccessReview Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development
Pharmaceuticals 2010, 3(7), 2090-2110; doi:10.3390/ph3072090
Received: 10 June 2010 / Revised: 28 June 2010 / Accepted: 2 July 2010 / Published: 5 July 2010
Cited by 7 | PDF Full-text (159 KB) | HTML Full-text | XML Full-text
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
Open AccessReview Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications
Pharmaceuticals 2010, 3(6), 1909-1935; doi:10.3390/ph3061909
Received: 26 April 2010 / Revised: 11 May 2010 / Accepted: 9 June 2010 / Published: 11 June 2010
Cited by 27 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the [...] Read more.
In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
Open AccessReview Natural Products in Epilepsy—the Present Situation and Perspectives for the Future
Pharmaceuticals 2010, 3(5), 1426-1445; doi:10.3390/ph3051426
Received: 22 April 2010 / Accepted: 11 May 2010 / Published: 12 May 2010
Cited by 8 | PDF Full-text (94 KB) | HTML Full-text | XML Full-text
Abstract
More efficacious and better tolerated treatments for epilepsy are clearly needed. Complementary and alternative medicine (CAM) has a long history of use in certain parts of the world and has gained increasing interest over the last decades in Western countries. In countries [...] Read more.
More efficacious and better tolerated treatments for epilepsy are clearly needed. Complementary and alternative medicine (CAM) has a long history of use in certain parts of the world and has gained increasing interest over the last decades in Western countries. In countries with a Western-based type of medical system, people with epilepsy (PWE) take natural products or engage in other forms of CAM mainly to enhance general health, but also to prevent seizures or to alleviate symptoms of comorbidities or side effects of antiepileptic medications. In other countries, well developed medical systems, such as traditional Chinese Medicine and Ayurveda, are often the basis for treating PWE. Based on anecdotal reports of efficacy in PWE, natural products from these and other traditions are increasingly being studied in animal models of epilepsy, and candidates for further clinical development have been identified. It is likely, therefore, that natural products will be further evaluated for safety, tolerability and efficacy in PWE with drug-resistant seizures. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)

Other

Jump to: Review

Open AccessCommentary Comments on the Eslicarbazepine Acetate Section of the Article ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’
Pharmaceuticals 2010, 3(12), 3629-3632; doi:10.3390/ph3123629
Received: 9 November 2010 / Accepted: 16 December 2010 / Published: 17 December 2010
Cited by 1 | PDF Full-text (49 KB) | HTML Full-text | XML Full-text
Abstract
The recent review of Matthew D. Krasowski on ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’ is a useful foundation of comparative interpretations on our current knowledge about therapeutic drug monitoring. Within the review, the statement that therapeutic drug monitoring has a [...] Read more.
The recent review of Matthew D. Krasowski on ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’ is a useful foundation of comparative interpretations on our current knowledge about therapeutic drug monitoring. Within the review, the statement that therapeutic drug monitoring has a minimal role in the therapeutic use of eslicarbazepine acetate due to its relatively predictable pharmacokinetics reflects the existing body of evidence although some information such as eslicarbazepine acetate’s chemical structure, proportions of its metabolites, their pharmacokinetics and chiral method of plasma level measurement need to be revised. These critical characteristics differentiate the novel compound from former dibenzazepines such as carbamazepine and oxcarbazepine in its clinical effects and needs for therapeutic drug monitoring. Full article
(This article belongs to the Special Issue Antiepileptic Drugs)
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