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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a short historical review of the development of the pharmaceutical treatment of the epilepsies the author reviews some of the possible strategies to manage patients with the different types of epilepsies and epileptic syndromes using the classical drugs. A strategy used by most of the physicians uses Sodium Valproate as the first line drug for almost all patients. This may be replaced by other drugs according to their efficacy against the different types of seizures to be treated whenever VPA has not enough efficacy or isn t well tolerated. On the other hand epileptologists use the different drugs according to the different epilepsies and epileptic syndromes depending on the relative efficacy of each drug available and the possible side effects. He then describes succinctly the better-known new drugs and makes some comments on the coming drugs now in development. Finally he proceeds to include them in the strategies above described. Lamotrigine and possibly Topiramate are good candidates to replace VPA in the one drug strategy. Lamotrigine, Oxcarbamazepine and possibly Gabapentin may be used in the future as 1st line drugs in selected patients. Vigabatrin is already used as one of the better alternatives for West syndrome and Oxcarbamazepine has replaced Carbamazepine in countries where it s available to the public. Some drawbacks have been apparent with these drugs like the hepatic and haematological toxic effect of Felbamate or the apparently irreversible fields constriction provoked by Vigabatrin, which did limit their use.
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PMID:The new drugs and the strategies to manage epilepsy. 1082 13

During the past few years, a number of drugs have been added to the anti-epileptic arsenal. This review focusses on five of these drugs which have undergone extensive trials: Vigabatrin, Lamotrigine, Gabapentin, Felbamate and Oxcarbazepine. Some of these antiepileptic drugs appear to be helpful for treatment of catastrophic childhood epilepsies. Vigabatrin appears promising in children with infantile spasms who do not respond to ACTH or Prednisolone. Children with Lennox-Gastaut syndrome may respond to treatment with Lamotrigine or Vigabatrin. Gabapentin and vigabatrin have proved to be effective in refractory partial seizures. Oxcarbazepine, a ketoderivative of carbamazepine, is as effective as Carbamazepine but has a better safety profile. Lesser neurotoxicity and fewer drug interactions is another advantage with these drugs. However monitoring is required to determine the long term safety with their usage. These drugs have a definite role in childhood epilepsies refractory to conventional antiepileptic drugs.
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PMID:Newer anti-epileptic drugs. 1082 95

Gabapentin is a relatively new anticonvulsant indicated for adjunctive therapy in the treatment of partial seizures, with and without secondary generalization, in adults with epilepsy. Overall, it has a minimal side effect profile compared with other anticonvulsant agents. Postmarketing surveillance is needed to further delineate the spectrum of adverse events that may be experienced by patients treated with this medication. This is a case report of a 25-year-old man with a 10-year history of mood swings that progressively worsened and resulted in a suicide attempt 8 months before his first appointment. A diagnosis of bipolar disorder was established, and a clinical interview ruled out other mental disorders. The patient was administered gabapentin 300 mg/day, and the dose was titrated upward to 900 mg/day. A follow-up appointment revealed improved control of his bipolar symptoms. However, the patient reported that he could not have an orgasm during sexual intercourse. The medication was changed to valproic acid 250 mg three times daily. His bipolar symptoms remained under control and the anorgasmia resolved. This was maintained at the next follow-up appointment. The side effect profile and therapeutic monitoring requirements of gabapentin are favorable when compared with those of other anticonvulsant agents. However, because this agent is relatively new, especially for use in the treatment of bipolar disorder, a more thorough development of its side effect profile is needed. Observing, recording, and reporting atypical adverse events and side effects are critical to postmarketing surveillance and enhance the clinician's ability to make rational therapeutic decisions.
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PMID:Anorgasmia in a patient with bipolar disorder type 1 treated with gabapentin. 1083 Oct 28

Decreased activity of gamma-aminobutyric acid, the major inhibitory neurotransmitter in CNS can be epileptogenic. Manipulation of the GABA system has been a target for development of antiepileptic drugs. The different ways for augmenting gabaergic inhibition by conventional and new AEDs are presented in this paper. Among the I generation, barbiturates and benzodiazepines are potent anticonvulsants that act as GABA modulators in postsynaptic GABA-A receptor complex but their usefulness is limited by dependence and tolerance to antiseizure activity. The II generation drugs vigabatrin and tiagabine, and to some extent gabapentin have been developed by a rationale strategy and none of them exert direct action in GABA receptors. Only two former drugs exhibit selective, strictly defined activity: vigabatrine is an irreversible inhibitor of GABA-aminotransferase and tiagabine acts as a GABA-uptake inhibitor from synaptic cleft into neurons and glia. Gabapentin binds to a novel receptors in epileptogenic areas in CNS and enhances GABA turnover. Drugs with multiple mechanisms of action, felbamate and topiramate not only potentiate gabaergic inhibition in several ways but also diminish the activity of excitatory amino acids at their NMDA or AMPA receptors; the later mechanism seems to be essential for their potential neuroprotective activity in epileptogenesis. None of gabamimetic drugs provide optimal seizure control but better tolerability of newer ones and well-established mechanisms of action provide possible harmless therapy.
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PMID:[The role of gamma-aminobutyric acid in the mechanism of action of anticonvulsant drugs]. 1084 11

The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.
Seizure 2000 Jun
PMID:Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group. 1088 Feb 82

A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to vigabatrin, such as encephalopathy, aphasia and motor disturbances. Vigabatrin-induced visual field constriction is the latest and most worrying ADR. Many questions regarding the nature of this potentially serious ADR remain unanswered, as no prospective controlled study examining the phenomenon has been published. Rare cases of behavioural ADRs and IgA and IgG2 deficiency associated with the use of zonisamide have been reported. However, relatively few patients so far have been exposed to this drug, and therefore more postmarketing information is required. The relatively late establishment of aplastic anaemia and hepatic failure as potentially fatal ADRs of felbamate, and of visual field constriction with vigabatrin, should serve as ample reminders that ADRs can appear at any time.
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PMID:Adverse reactions to new anticonvulsant drugs. 1091 31

Gabapentin has been shown to reduce paired-pulse inhibition in the dentate gyrus of the urethane-anesthetized rat and has been shown to block calcium channels, but its not known how these possible mechanisms relate to its antiepileptic effect. Here, we tested two structural analogs of gabapentin for the ability to reduce seizure duration and to alter paired-pulse inhibition in the dentate gyrus in urethane anesthetized adult Sprague-Dawley rats. We compared with our results to those with diazepam, an anxiolytic and GABA(A) positive modulator and with nimodipine, a specific blocker of L-type Ca2+ channels. Both structural analogs of gabapentin caused a dose-dependent loss of paired-pulse inhibition and blocked the lengthening of the duration of the seizure discharge. Nimodipine also blocked the increase in duration of the seizure discharge, but increased paired-pulse inhibition. The effects of the GABA derivatives on paired-pulse inhibition and on seizure duration may have a common mechanism. Furthermore, our results indicate that gabapentin's postulated block of L-type calcium channels is not responsible for reducing paired-pulse inhibition. However, calcium channel block could still be the basis for the antiepileptic effect of gabapentin and its analogs.
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PMID:The effects of gabapentin in the rat hippocampus are mimicked by two structural analogs, but not by nimodipine. 1094 Jun 16

Epilepsy is common in the elderly. The incidence of epilepsy is age-dependent, with a peak during the first year of life and higher incidence in those older than 75 years. Cerebrovascular disease is a common cause of epilepsy in the elderly. Drug treatment of the elderly is a challenge because of pharmacokinetic changes with aging, including impaired drug protein binding or displacement of drug from protein binding sites, potentially causing drug toxicity as a result of increased free drug concentrations. With aging, hepatic mass and blood flow decline along with renal function. Established anticonvulsant drugs have adverse effects and drug interactions that can make treating the elderly difficult. Newly available anticonvulsants cause fewer drug-drug interactions and less toxicity. Gabapentin is not metabolised, is not bound to protein, and has a favourable adverse effect profile and thus may be useful in the treatment of elderly patients. Lamotrigine reduced seizures between 20 and 30% in trials. Dose response was between 300mg per day and 500mg per day. This drug was well tolerated in open-label trials. Rash occurred in younger patients. Oxcarbazepine is rapidly absorbed and is converted to a monohydroxy derivative. Use with hepatic enzyme-inducing drugs necessitates an increase in dose. This drug may be substituted for carbamazepine. Hyponatraemia has been reported and monitoring is suggested. Topiramate blocks voltage-dependent sustained repetitive firing and has an effect on the gamma-aminobutyric acid (GABA) receptors. It affects glutamate responses and inhibits carbonic anhydrase. Topiramate has a dose response pattern up to 400mg per day. Cognitive effects limits its use in some patients. Nephrolithiasis has occurred with this drug. Tiagabine blocks GABA transporter proteins. Clearance is rapid and metabolism complete. Hepatic dysfunction prolongs clearance. The use of tiagabine has not been reported in the elderly. Zonisamide is rapidly absorbed and protein binding is 50%. Plasma half-life is 55 hours but is reduced to about 30 hours by hepatic enzyme-inducing drugs. Responder rate is 45%. Adverse effects include drowsiness, altered thinking and nephrolithiasis. Treatment of the elderly requires obligatory polypharmacy with potential drug interactions. Changes in body physiology alter absorption, binding, metabolism and elimination of drugs. Concomitant illness and sensitivity to drug effects narrow the therapeutic range and complicate pharmacokinetics in elderly patients. Newer anticonvulsant drugs have advantages that may outweigh risks and have therapeutic profiles that may aid in the treatment of this special population of patients.
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PMID:Choice and use of newer anticonvulsant drugs in older patients. 1120 Mar 5

Gabapentin is a recently introduced anti-epileptic drug used as an adjuvant in partial and secondarily generalised tonic-clonic seizures. Its mechanism of action has not been fully elucidated, but it seems that gabapentin may regulate voltage-dependent calcium channels, presumably on a spinal level, in the nociceptive system. Two large, controlled clinical trials of painful diabetic neuropathy and postherpetic neuralgia have demonstrated its analgesic efficacy. The adverse effects associated with gabapentin treatment are relatively harmless, mild to moderate in severity, and usually transient, with tolerance developing 2-3 weeks after start of treatment. Gabapentin and tricyclic antidepressants are efficacious in the treatment of painful diabetic neuropathy and postherpetic neuralgia.
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PMID:[Gabapentin--yet another antiepileptic agent for the treatment of neuropathic pain?]. 1121 87

Gabapentin, which has been approved for add-on therapy of focal seizures, is increasingly used for treatment of neuropathic pain. Its analgesic effect is supposed to be due to reduction of glutamatergic transmission, improvement of GABAergic transmission and to binding to voltage-dependent calcium channels. Experimental studies demonstrated an ameliorating effect of gabapentin on neuropathic pain. Placebo-controlled studies revealed an efficacy of gabapentin against pain in diabetic neuropathy and postherpetic neuralgia and in prophylaxis of migraine. Case reports show an analgesic effect of gabapentin in trigeminus neuralgia and in reflex sympathetic dystrophy. The main adverse events are dizziness, ataxia and somnolence. Controlled studies, which compare the efficacy of gabapentin with that of the respective reference drug, are needed to evaluate its importance in treatment of pain.
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PMID:[Gabapentin therapy for pain]. 1125 57


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