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[癫痫的治疗策略]

[Therapeutic strategies in epilepsy].

作者信息

Pimentel J

机构信息

Serviço de Neurologia, Hospital de Santa Maria, Lisboa.

出版信息

Acta Med Port. 1997 Aug-Sep;10(8-9):573-9.

PMID:9446476
Abstract

With the advances in the so-called classic antiepileptic drugs (AED)--carbamazepine, phenobarbital, phenytoin and valproate--monotherapy has become the most popular strategy for the treatment of epilepsies, based on their unquestionable clinical efficacy and on frequent drug interactions and teratogenesis caused by polypharmacy. The choice of an AED should be ruled by its efficacy against a given seizure type; by its toxicity, either acute, dose-related or idiosyncratic, or chronic, due to the length of therapy or AED dosage; by its capacity to interact with other drugs, either AEDs or not, mainly through pharmacokinetic interactions, leading to fluctuation in the plasma concentration of the target drug and hence decreased in their efficacy; by its potential cognitive and behavioural side effects; by its teratogenesis which is common to all AEDs; by its cost. Despite their efficacy, about 35% of the patients are inadequately treated with monotherapy, partial, symptomatic or associated to encephalopathy being the most frequent of their seizures. For this particular group, the association of two AEDs could play an important role. The increasing knowledge of the mechanisms of the new generation of AEDs, such as vigabatrin and lamotrigine, and their favourable pharmacokinetic and pharmacodynamic profiles, rise to the new concept of rational polytherapy which allows an additive or supra-additive therapeutic efficacy, a limited toxicity, a decrease in drug interactions and an increased compliance. Although monotherapy should continue to be the choice therapy for epilepsies, this concept could be a reasonable and early option in the treatment of some refractory epilepsies.

摘要

随着所谓经典抗癫痫药物(AEDs)——卡马西平、苯巴比妥、苯妥英和丙戊酸盐——的进展,基于其无可置疑的临床疗效以及多药联合治疗导致的频繁药物相互作用和致畸作用,单药治疗已成为治疗癫痫最常用的策略。选择一种抗癫痫药物应依据其对特定癫痫发作类型的疗效;依据其毒性,包括急性毒性、剂量相关毒性或特异质性毒性,以及由于治疗时间或抗癫痫药物剂量导致的慢性毒性;依据其与其他药物(无论是否为抗癫痫药物)相互作用的能力,主要通过药代动力学相互作用,导致目标药物血浆浓度波动,进而降低其疗效;依据其潜在的认知和行为副作用;依据其致畸作用(这是所有抗癫痫药物共有的);依据其成本。尽管这些药物疗效显著,但约35%的患者接受单药治疗效果不佳,部分性发作、症状性发作或与脑病相关的发作是其最常见的癫痫发作类型。对于这一特定群体,两种抗癫痫药物联合使用可能发挥重要作用。对新一代抗癫痫药物(如氨己烯酸和拉莫三嗪)作用机制的了解不断增加,以及它们良好的药代动力学和药效学特征,催生了合理联合治疗的新概念,这种联合治疗具有相加或超相加的治疗效果、有限的毒性、减少药物相互作用以及提高依从性。尽管单药治疗仍应是癫痫的首选治疗方法,但这一概念在某些难治性癫痫的治疗中可能是一种合理且早期的选择。

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