癫痫的药物治疗

癫痫是一种神经系统的常见病，我国目前约有600万癫痫患者。对于癫痫的治疗应着重于三个方面：病因和诱发因素的治疗；对癫痫患者的教育和社会照料；癫痫症状的控制。这三个方面中，控制发作是最主要的目标。癫痫发作的控制有药物治疗和手术治疗，目前药物控制仍是主要的治疗手段。     

抗癫痫药物监测

癫痫是神经系统的常见疾病。抗癫痫药物(antiepileptic drugs，AEDs)大多治疗窗窄，药动学个体间和个体内差异大，同时癫痫治疗需要长期用药，AEDs须进行治疗药物监测(therapeutic drug monitoring，TDM)和个体化给药。现通过文献查阅和临床实践，对AEDs监测的方法和意义作一综述。     

综合性医院门诊抗高血压药的药物利用研究

目的 了解抗高血压药的临床应用模式,并促进其合理用药。方法 利用医院信息系统药房管理子系统,对2008年11月14日-11月18日某综合性医院门诊患者含抗高血压药的处方进行回顾性分析。合理性标准为药品说明书、国内外循证医学研究结果、药物代谢酶学和2007年欧洲高血压治疗指南。结果 该院的抗高血压药治疗应用总体较为合理,较好地符合治疗指南。极少量处方在用法用量和合并用药方面的合理性值得商榷。结论 临床医生和药师应遵循药物治疗指南,注意鉴别潜在的相互作用,做好患者用药教育和抗高血药药物治疗达标管理。应用药动学原理,可以有效指导临床合理选药。对于多重用药患者可以加强药物治疗监测,必要时换用替代药品等。     

综合性医院门诊抗高血压药的药物利用研究

目的了解抗高血压药的临床应用模式,并促进其合理用药。方法利用医院信息系统药房管理子系统,对2008年11月14日—11月18日某综合性医院门诊患者含抗高血压药的处方进行回顾性分析。合理性标准为药品说明书、国内外循证医学研究结果、药物代谢酶学和2007年欧洲高血压治疗指南。结果该院的抗高血压药治疗应用总体较为合理,较好地符合治疗指南。极少量处方在用法用量和合并用药方面的合理性值得商榷。结论临床医生和药师应遵循药物治疗指南,注意鉴别潜在的相互作用,做好患者用药教育和抗高血药药物治疗达标管理。应用药动学原理,可以有效指导临床合理选药。对于多重用药患者可以加强药物治疗监测,必要时换用替代药品等。     

影响抗癫痫药物治疗效果的因素分析

癫痫是由各种不同原因引起的脑的慢性疾病。流行病学调查结果〔1〕,我国癫痫发病率在 2 5～ 4 0 / 1 0万·年 ,国外 2 5～5 0 / 1 0万·年。患病率为 3‰～ 6‰。癫痫作为一种常见病、多发病 ,通常需要长期药物治疗。据报道其有效控制率已达 75 %～ 85 % 〔2〕,但在我们实际工作中却常常出现发作不能完全控制和疗效不佳的情况。病人和家属对治疗失去信心 ,心理负担很重。这往往不是单纯靠药物治疗所能解决的。根据我们多年的工作经验 ,结合文献资料分析 ,认为有以下几个方面因素影响癫痫的治疗效果。1 　 由于不能正确诊断确定癫痫发作类型 …     

抗癫痫药物的相互作用

抗癫痫药物的相互作用安儒峰王立兰董进和郭丰广（泰山医学院附属医院泰安２７１０００）多数癫痫患者需长期服用抗癫痫药物来控制病情，而抗癫痫药物（ＡＥＤ）间的相互作用错综复杂，故安全合理地使用ＡＥＤ是药物治疗癫痫的关键。本文着重介绍近年来新发展的ＡＥＤ间的...     

体内药物相互作用机制及其评价方法的研究进展

药物–药物相互作用是目前临床不良反应的主要来源之一,药物相互作用产生的效益和风险会严重影响药物的安全性和有效性。根据药物在体内的过程,分别从吸收、分布、代谢、排泄4个方面阐述了体内药物相互作用机制并佐以实例;潜在药物相互作用的研究以预测其可能发生的药物相互作用也已成为药物开发的必须过程,综述了近些年比较成熟的药物相互作用评价模型的及其研究进展。     

治疗药物监测的研究进展

本文对治疗药物监测的药物如中药、抗癫痫药、免疫抑制药、抗逆转录病毒药物、抗精神病药物、抗肿瘤药物和抗微生物药物的最新研究进展进行综述,介绍其方法学上的最新进展,如利用液质联用将成为发展方向。结合群体药动学和药物遗传学的最新发展,研究疾病药物治疗中的新方法,指导临床个体化用药,提出治疗药物监测(TDM)新的发展方向,如利用基因分型和基因芯片对患者测定基因型,以指导临床合理用药。     

左乙拉西坦——一种具有全新作用机制的抗癫痫新药

左乙拉西坦是一种新型的口服抗癫痫药物,与其他抗癫痫药物的结构不同,具有全新的抗癫痫机制。左乙拉西坦的确切抗癫痫机制尚不明,但与传统抗癫痫药物作用于离子通道或兴奋性、抑制性神经递质系统不同。左乙拉西坦几乎具备了较好的抗癫痫药物的所有药动学特性:生物利用度高、线性曲线、低蛋白结合率、无肝酶诱导作用。多种动物模型显示左乙拉西坦具有抗癫痫特性。全球范围的3个重要多中心、随机、双盲、安慰剂对照临床试验结果显示左乙拉西坦具有确切的抗癫痫疗效和很好的耐受性,可用于治疗癫痫、神经痛和其他神经系统疾病。     

新型抗癫痫药之间及其与传统抗癫痫药的相互作用和机制*

分别综述了几种新型抗癫痫药（托吡酯、非氨酯、奥卡西平、拉莫三嗪、唑尼沙胺、左乙拉西坦、噻加宾、加巴喷丁及氨己烯酸）与传统抗癫痫药联合应用时以及这些新型抗癫痫药之间的相互作用及其发生机制，阐明细胞色素P450酶和葡萄糖苷酸转移酶在新型抗癫痫药的相互作用中的意义及重要性。为临床合理联合应用提供理论依据，提高抗癫痫治疗的可靠性、安全性和有效性。     

Pharmacology of antiepileptic drugs in the gerbil—I. Pharmacokinetics

Pharmacokinetic data for antiepileptic drugs were determined in gerbils. The drugs had the following elimination half-lives: phenytoin 2.1 hr; phenobarbital 10.6 hr; carbamazepine 1.8 hr; valproate 0.69 hr; ethosuximide 1.4 hr and diazepam 1.15 hr. Diazepam was predominantly metabolized via 3-hydroxydiazepam to oxazepam which had the longest half-life (2 hr) of the metabolites.     

Therapeutic drug monitoring – antiepileptic drugs

Aims  To provide a brief critical review of the basis and contemporary practice of monitoring the concentrations of antiepileptic drugs in biological fluids.
Methods  The review is based on literature data and observations from clinical practice.
Results  As experience has accumulated, monitoring of antiepileptic drug concentrations has come to be applied mainly to certain of the drugs when present in whole plasma. For these drugs there is a reasonably established relationship between drug concentrations and biological effects, but attention still needs to be paid to issues such as the timing of the measurements in relation to drug intake, the presence or absence of steady-state conditions, the presence in plasma of active metabolites and possible nonlinear pharmacokinetics of particular agents, e.g. phenytoin.
Conclusions  Plasma antiepileptic drug concentration monitoring is coming to be used in a more thoughtful and critical manner. Lack of adequate knowledge of matters such as the relationship between the plasma concentrations and antiepileptic and toxic effects of the drugs, not only the newer, but also the longer established ones, in particular clinical situations, remains more important than deficiencies in analytical methodology in limiting the clinical usefulness of antiepileptic drug concentration monitoring.     

New and investigational antiepileptic drugs

In the last fifteen years, new antiepileptic medications have been offered for the treatment of patients with epilepsy. Nevertheless, despite optimal medical treatment, up to 30% of patients still experience recurrent seizures and the challenge for new, more efficacious and better-tolerated drugs continues. New antiepileptic drugs include the evolution of pre-existing drugs and new compounds identified through the investigation of additional molecular targets, such as SV2A synaptic vesicle protein, voltage-gated potassium channels, ionotropic and metabotropic glutamate receptors, and gap junctions. This paper reviews the available information on various classes of molecules that are in the pipeline as well as on the innovative approaches to the treatment of epilepsy.     

Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children

1   Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication.
2   This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively.
3   Thirty-one children aged 6 months to 5 years were included and received a 2  mg  kg⁻¹ single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean±s.d.) were: 7.7±1.8  h, 21.9±6.8  h, 44.7±10.2  h in the 'inducer', 'other' and 'inhibitor' groups respectively.
4   Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3  mg  l⁻¹. The mean minimum plasma concentration for the three groups was 2.54±1.28  mg l⁻¹ at steady state.
5   Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.     

393例抗癫痫药物血药浓度监测结果分析

目的通过分析该院抗癫痫药物血药浓度监测分析的结果,为临床合理用药提供参考。方法运用高效液相色谱法,对丙戊酸钠、苯妥英钠、卡马西平、苯巴比妥在393例病人中的血药浓度进行测定,并对结果进行统计分析。结果丙戊酸钠(50～100 mg.L-1)、卡马西平(4～12 mg.L-1)、苯妥英钠(10～20 mg.L-1)、苯巴比妥(15～40 mg.L-1)在有效血药浓度范围内的例数分别为:111例(76.55%)9、3例(77.50%)、41例(73.21%)、52例(72.22%)。结论抗癫痫药物血药浓度监测结果显示,临床用药应综合考虑各方面因素,实施个体化给药方案,确保用药安全有效。     

Psychiatric symptomatologies and disorders related to epilepsy and antiepileptic medications

Introduction: Psychiatric comorbidities (such as depression, anxiety, psychosis, inattention, obsession, personality traits, aggression and suicide) are frequent in patients with epilepsy and have a significant impact on medical management and quality of life.

Areas covered: A literature search was performed in MEDLINE for epidemiological, longitudinal, prospective, double-blind clinical trial studies published between 1990 and 2011 using the following words: epilepsy, antiepileptic drugs (AEDs), behavioral/emotional/psychiatric comorbidities, suicide and aggression. In this review, the author discusses: i) the characterization and prevalence of behavioral disturbances associated with epilepsy, ii) variables correlated with behavioral comorbidities which include: psychosocial-, clinical- and treatment-related variables, iii) the complex mechanisms of behavioral comorbidities associated with epilepsy, which include both psychosocial (functional) and organic; the process of epileptogenesis, neuronal plasticity, abnormalities in hypothalamic-pituitary axis and neurotransmitters and pathways are fundamental determinants, iv) the negative psychotropic effects of AEDs and their mechanisms and v) the suggested biopsychosocial model of management (pharmacological and non-pharmacological).

Expert opinion: The relationship between psychiatric disorders and epilepsy has relevant therapeutic implications which should be directed towards a comprehensive biopsychosocial approach that focuses on the whole person rather than simply on the disease process.     

Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update

This article aims to summarize the current views of AED action and the promising new targets for the pharmacotherapy of epilepsy. In the first section of this paper, a neurobiological basis of epilepsy treatment and brief pharmacological characteristics of classical and new AEDs will be presented. In the second part, the results of experimental studies that have combined AEDs with similar or different mechanisms of action will be discussed.