The new antiepileptic drugs: clinical applications

In the past decade, 8 new antiepileptic drugs have been approved for use in the United States, offering many new treatment options to patients with epilepsy. With expanding use of these newer agents, primary care clinicians are challenged with understanding the roles that each new agent plays in the treatment of patients with epilepsy as well as possible interactions with other pharmacological therapies. Each new medication provides a unique profile of pharmacokinetics, adverse effects, and mechanisms of action, making an appreciation of how these agents are best utilized even more difficult. Despite well-performed trials evaluating the safety and efficacy of specific antiepileptic drugs, the lack of head-to-head comparisons among them makes it difficult to endorse a single therapeutic regimen. Limited studies have compared the new antiepileptic drugs with more traditional medications and found similar efficacy but improved tolerability of the newer agents. There remains no well-established guidelines for choosing a particular antiepileptic drug or for choosing a newer agent over a traditional one. However, careful consideration of seizure type, patient comorbidities, and specific medication toxicities aids in prescribing the most appropriate medication. This article aims to familiarize the general practitioner with the appropriate roles and effective uses of the new antiepileptic drugs in specific clinical scenarios.      

传统抗癫痫药物与新型抗癫痫药物对认知功能的影响

目的 评价传统抗癫痫药物代表丙戊酸钠与新型抗癫痫药物代表对癫痫患者认知功能的影响.方法 将80例癫痫患者随机分为丙戊酸钠组与拉莫三嗪组,利用韦氏智能测定,分别于治疗前及用药6个月后对患者认知功能进行统计分析.结果 两组癫痫患者用药前语言智商(VIQ)操作智商(PIQ)总智商(FIQ)分值无明显差异;在用药6个月,丙戊酸钠组,语言智商(VIQ)操作智商(PIQ)总智商(FIQ)分值明显下降,而拉莫三嗪无明显变化,两组结果具有统计学意义(P<0.05).结论 丙戊酸钠对患者认知功能有影响,而拉莫三嗪对患者认知功能无明显影响.     

抗癫痫药物的研究进展

癫痫是神经系统的一种常见病，我国目前约有600万癫痫患。对于癫痫的治疗应着重于3个方面：病因和诱发因素的治疗；对癫痫患的教育和社会照料；癫痫症状的控制。在这3个方面中，控制发作是最主要的目标。癫痫发作的控制可分为药物治疗和手术治疗，目前药物控制仍是主要的治疗手段。本对癫痫治疗药物的研究进展综述如下。     

新一代抗癫痫药对新生大鼠脑发育的影响

目的探讨新一代抗癫痫药一次性单药或联合苯巴比妥(PB)用药对新生大鼠脑发育的影响。方法将健康清洁级7日龄Wistar大鼠270只随机分为对照组、奥卡西平(OXC) 30组、OXC60组、托吡酯(TPM)组、左乙拉西坦(LEV)组、PB组、PB+OXC30组、PB+TPM组和PB+LEV组,每组30只。OXC30组、OXC60组、TPM组、LEV组和PB组大鼠分别灌胃OXC 187. 5 mg·kg-1、OXC 375. 0 mg·kg-1、TPM 62. 5 mg·kg-1、LEV 375. 0 mg·kg-1、PB62. 5 mg·kg-1; PB+OXC30组、PB+TPM组和PB+LEV组大鼠均腹腔注射PB 62. 5 mg·kg-1,4 h后,再分别灌胃OXC 187. 5 mg·kg-1、TPM 62. 5 mg·kg-1、LEV 375. 0 mg·kg-1;对照组大鼠腹腔注射生理盐水0. 1 m L。每组取10只大鼠测给药前后体质量及给药后脑质量;给药后24 h,每组取10只大鼠采用苏木精-伊红(HE)、尼氏染色观察大鼠脑组织病理学改变;给药后16 d,每组取10只大鼠行Morris水迷宫试验检测大鼠学习记忆能力;水迷宫试验结束后次日处死大鼠,取脑组织观察病理学改变,并进行颞叶皮层及海马下托复合体神经细胞计数。结果用药前各组大鼠体质量比较差异无统计学意义(P> 0. 05);给药后24 h,OXC60组、PB+OXC30组、PB+TPM组、PB+LEV组及PB组大鼠体质量均低于对照组(P <0. 05); OXC30组、TPM组、LEV组与对照组大鼠体质量比较差异无统计学意义(P>0. 05)。PB+OXC30组、PB+TPM组、PB+LEV组与PB组大鼠体质量比较差异均无统计学意义(P> 0. 05)。OXC60组、PB+OXC30组大鼠脑质量显著低于对照组(P <0. 05);其余各给药组大鼠脑质量与对照组比较差异均无统计学意义(P> 0. 05)。PB+OXC30组、PB+TPM组、PB+LEV组大鼠脑质量与PB组比较差异均无统计学意义(P>0. 05)。给药后24 h,HE染色可见,各给药组大鼠脑组织颞叶皮层结构未见明显异常。OXC60组、PB组、PB+OXC30组、PB+TPM组及PB+LEV组大鼠脑组织海马下托复合体出现部分细胞核固缩、深染,核周空泡,细胞皱缩等病理学改变,且PB+OXC30组病变严重程度明显大于PB组; OXC30、TPM、LEV组大鼠脑组织海马下托均未见明显病理改变。尼氏染色显示,OXC60组、PB+OXC30组、PB+TPM组及PB+LEV组大鼠脑组织颞叶皮层少数神经细胞尼氏小体减少,部分溶解消失; OXC60组和PB组大鼠海马下托可见尼氏小体减少,部分溶解。给药后23 d,PB+OXC30组大鼠脑组织颞叶皮层可见退行性红色神经细胞明显增多; PB+TPM组、PB+LEV组及OXC60组大鼠脑组织病理学改变有所恢复。OXC60组和PB+OXC30组大鼠穿越平台次数少于对照组(P <0. 05)。OXC30组、TPM组、LEV组、PB组、PB+TPM组和PB+LEV组与对照组大鼠穿越平台次数比较差异无统计学意义(P> 0. 05); PB+OXC30组、PB+TPM组和PB+LEV组与PB组大鼠穿越平台次数比较差异无统计学意义(P> 0. 05)。第1、2、3、4天,各给药组与对照组大鼠寻台潜伏期比较差异均无统计学意义(P> 0. 05)。PB+OXC30组大鼠第5天寻台潜伏期长于对照组(P <0. 05),其余各给药组与对照组大鼠第5天寻台潜伏期比较差异均无统计学意义(P> 0. 05)。第1、2、3、4、5天,PB+OXC30组、PB+TPM组、PB+LEV组与PB组大鼠寻台潜伏期比较差异无统计学意义(P> 0. 05)。各给药组与对照组大鼠颞叶皮层神经细胞计数比较差异均无统计学意义(P> 0. 05)。PB+OXC30组大鼠海马下托区神经细胞计数少于对照组(P <0. 05),其余各组大鼠海马下托区神经细胞计数与对照组比较差异均无统计学意义(P> 0. 05)。PB+OXC30组、PB+TPM组、PB+LEV组与PB组大鼠海马下托区神经细胞计数比较差异无统计学意义(P> 0. 05)。结论一次性使用375. 0 mg·kg-1OXC可导致新生健康大鼠急性期脑损伤和远期空间记忆能力稍减弱;较低剂量(187. 5 mg·kg-1)的OXC不会引起发育未成熟脑出现明显损伤,但却能明显加重PB引起的脑损伤,且遗留持久性脑损伤和记忆功能障碍;抢救剂量的LEV (375. 0 mg·kg-1)和TPM (62. 5 mg·kg-1)不存在脑损伤危险,也不加重PB引起的损伤。     

Liquid chromatographic methods for determination of the new antiepileptic drugs stiripentol,retigabine, rufinamide and perampanel: A comprehensive and critical review

The new antiepileptic drugs perampanel, retigabine, rufinamide and stiripentol have been recently approved for different epilepsy types. Being them an innovation in the antiepileptics armamentarium, a lot of investigations regarding their pharmacological properties are yet to be performed. Besides, considering their broad anticonvulsant activities, an extension of their therapeutic indications may be worthy of investigation, especially regarding other seizure types as well as other central nervous system disorders. Although different liquid chromatographic (LC) methods coupled with ultraviolet, fluorescence, mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel, retigabine, rufinamide and stiripentol, new and more cost-effective methods are yet required. Therefore, this review summarizes the main analytical aspects regarding the liquid chromatographic methods developed for the analysis of perampanel, retigabine (and its main active metabolite), rufinamide and stiripentol in biological samples and pharmaceutical dosage forms. Furthermore, the physicochemical and stability properties of the target compounds will also be addressed. Thus, this review gathers, for the first time, important background information on LC methods that have been developed and applied for the determination of perampanel, retigabine, rufinamide and stiripentol, which should be considered as a starting point if new (bio)analytical techniques are aimed to be implemented for these drugs.     

抗癫痫类药物的血药浓度监测结果分析

目的分析抗癫痫药物(AEDs)临床疗效与血药浓度之间的关系,为临床合理用药提供个体化用药参考,探讨如何开展抗癫痫类药血药浓度监测后的药学服务。方法采用酶扩增均相免疫分析法(EMIT)监测抗癫痫类药物丙戊酸钠(VPA)、苯妥英钠(PHT)、卡马西平(CBZ)血药浓度,回顾性调查、统计分析2009-2011年945例次VPA、278例次PHT、157例次CBZ血药浓度监测结果。结果其中55.3%的患者VPA监测结果在有效参考血药浓度范围以内,31.7%的患者PHT监测结果在有效血药浓度范围以内,79.0%的患者CBZ监测结果在有效参考血药浓度范围内。结论抗癫痫药物血药浓度监测是临床用药的依据之一,临床药师于血药浓度监测后为患者提供个体化给药建议,对合理用药有重要的指导意义。     

抗癫痫药物与血脂异常相关性的Meta分析

目的 运用Meta分析方法评估抗癫痫药物与血脂异常的相关性,为合理选择抗癫痫药物及明确抗癫痫药物对血脂异常的不良影响提供更为有利的依据.方法 以"抗癫痫药"、抗惊厥药"及"血脂"为关键词对万方、维普及中国知网三大数据库建库至2017年3月所有文献进行检索.仅纳入关于抗癫痫药物与血脂异常的病例对照研究及队列研究.对所纳入的文献进行客观的评价质量后,采用RevMan5.3分析软件进行数据分析.结果 最终纳入18篇研究,共878例研究对象,涉及到的抗癫痫药物包括丙戊酸钠、卡马西平、苯妥英钠、苯巴比妥、拉莫三嗪及托吡酯.Meta分析结果示丙戊酸钠会导致总胆固醇(TC)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)水平的增加,差异具有显著统计学意义(P<0.01);卡马西平会增加TC、甘油三酯(TG)、HDL-C及LDL-C的水平,差异有显著统计学意义(P<0.01).苯妥英钠会降低TC、TG及LDL-C的血清水平,差异具有显著统计学意义(P<0.01).结论 抗癫痫药可能会改变癫痫患者血脂水平,尤其是卡马西平、丙戊酸钠及苯妥英钠.临床医生及癫痫患者都需提高对血脂异常的管理,从而避免血管疾病的发生.     

从左乙拉西坦到Brivaracetam——抗癫药物的发展趋势

癫是一种由不同原因引起的慢性脑部疾患,目前临床抗癫药物(AEDs)种类繁多,但仍有约30%癫患者性发作不能控制,需多种AEDs联合应用或加用新的AEDs。新的AEDs应具有好的临床效能、耐受性及药代动力学和最小的不良反应。目前新一代AEDs包括20种,大多为现有AEDs的衍生物,其中Brivaracetam(BRI)为左乙拉西坦(LEV)的衍生物。本文将从LEV及其衍生物BRI的作用机制、临床应用、耐受性、药理及毒理、不良反应等方面对AEDs发展趋势作一综述。     

Topiramate: a new safe and effective antiepileptic

Twenty patients of either sex, with refractory partial epilepsy with or without secondary generalisation were entered in an open label study to evaluate the efficacy and safety of topiramate in them. Topiramate was used as an adjunctive therapy with an initial starting dose of 50 mg/day. The dose was then titrated upwards with increments of 50 mg per week, till a time the most effective and the best tolerated dose was reached. This most effective/tolerated dose was then continued for 6 months. Of the 17 patients entering the maintenance phase, 4 patients (24%) became seizure free, while a total of 14 patients (83%) out of 17 cases responded with a reduction in monthly seizures rate by 50% or more. Mean reduction of 68.9% was observed in monthly seizure rate during the maintenance phase. The median effective dose of topiramate was 600 mg per day. Five patients dropped out of the study due to adverse events such as anxiety, aggressiveness, rash, lethargy, etc. The central nervous system (CNS) related side effects such as dizziness, headache, and tremor were reported, which are commonly seen with other presently available antiepileptics like carbamazepine, phenytoin sodium, sodium valproate, etc, as well. Most adverse events, however, were mild and transient and did not interfere with the day to day activity of the patients. Topiramate was not associated with any abnormality in laboratory or neurological examination findings. The excellent response with topiramate therapy in Indian patients, uncontrolled with the available antiepileptics, as well as its good safety profile endorse the international efficacious and safe image of topiramate.     

Colorectal cancer screening: scientific review

Context  Screening for colorectal cancer clearly reduces colorectal cancer mortality, yet many eligible adults remain unscreened. Several screening tests are available, and various professional organizations have differing recommendations on which screening test to use. Clinicians are challenged to ensure that eligible patients undergo colorectal cancer screening and to guide patients in choosing what tests to receive. Objective  To critically assess the evidence for use of the available colorectal cancer screening tests, including fecal occult blood tests, sigmoidoscopy, colonoscopy, double-contrast barium enema, and newer tests, such as virtual colonoscopy and stool-based molecular screening. Data Sources  All relevant English-language articles were identified using PubMed (January 1966-August 2002), published meta-analyses, reference lists of key articles, and expert consultation. Data Extraction  Studies that evaluated colorectal cancer screening in healthy individuals and assessed clinical outcomes were included. Evidence from randomized controlled trials was considered to be of highest quality, followed by observational evidence. Diagnostic accuracy studies were evaluated when randomized controlled trials and observational studies were not available or did not provide adequate evidence. Studies were excluded if they did not evaluate colorectal screening tests and if they did not evaluate average-risk individuals. Data Synthesis  Randomized controlled trials have shown that fecal occult blood testing can reduce colorectal cancer incidence and mortality. Case-control studies have shown that sigmoidoscopy is associated with a reduction in mortality, and observational studies suggest colonoscopy is effective as well. Combining fecal occult blood testing and sigmoidoscopy may decrease mortality and can increase diagnostic yield. Conclusion  The recommendation that all men and women aged 50 years or older undergo screening for colorectal cancer is supported by a large body of direct and indirect evidence. At present, the available evidence does not currently support choosing one test over another.      

375例抗癫痫药物血药浓度监测结果分析

目的 通过对抗癫痫药物血药浓度的监测,为调整药物剂量、评价药物不良反应和保证治疗效果提供依据。方法 采用荧光偏振免疫法及高效液相色谱法对未合并用药的138例服用丙戊酸、151例服用卡马西平、21例服用苯妥英、65例服用苯巴比妥的癫痫患者进行血药浓度监测。结果 丙戊酸、卡马西平、苯妥英和苯巴比妥有效血药浓度范围分别为50-100、4—12、10-20和15-40μg／mL,有效血药浓度范围内的控制率明显高于浓度范围外的控制率。苯妥英和苯巴比妥均有中毒病例发生。结论 血药浓度监测对抗癫痫药物的个体化给药十分必要,应紧密结合临床症状,做到安全、有效用药。