Willmore L J
Department of Neurology, Saint Louis University School of Medicine, Missouri 63104, USA.
Drugs Aging. 2000 Dec;17(6):441-52. doi: 10.2165/00002512-200017060-00002.
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.
癫痫在老年人中很常见。癫痫的发病率与年龄相关，在出生后第一年达到高峰，75岁以上人群的发病率更高。脑血管疾病是老年人癫痫的常见病因。由于衰老导致的药代动力学变化，老年人的药物治疗具有挑战性，这些变化包括药物蛋白结合受损或药物从蛋白结合位点被置换，可能因游离药物浓度增加而导致药物毒性。随着年龄增长，肝脏质量和血流量以及肾功能都会下降。已有的抗惊厥药物有不良反应和药物相互作用，这可能使老年人的治疗变得困难。新上市的抗惊厥药物引起的药物相互作用较少，毒性也较小。加巴喷丁不被代谢，不与蛋白质结合，不良反应较少，因此可能对老年患者的治疗有用。在试验中，拉莫三嗪使癫痫发作减少了20%至30%。剂量反应在每天300毫克至500毫克之间。在开放标签试验中，这种药物耐受性良好。皮疹在年轻患者中出现。奥卡西平吸收迅速，会转化为单羟基衍生物。与肝酶诱导药物合用时需要增加剂量。这种药物可以替代卡马西平。已有低钠血症的报道，建议进行监测。托吡酯可阻断电压依赖性持续重复放电，并对γ-氨基丁酸（GABA）受体有作用。它影响谷氨酸反应并抑制碳酸酐酶。托吡酯的剂量反应模式可达每天400毫克。认知效应限制了它在一些患者中的使用。使用这种药物会出现肾结石。噻加宾可阻断GABA转运蛋白。清除迅速，代谢完全。肝功能障碍会延长清除时间。尚未有关于老年人使用噻加宾的报道。唑尼沙胺吸收迅速，蛋白结合率为50%。血浆半衰期为55小时，但肝酶诱导药物可使其降至约30小时。有效率为45%。不良反应包括嗜睡、思维改变和肾结石。老年患者的治疗需要联合使用多种药物，这可能会产生药物相互作用。身体生理变化会改变药物的吸收、结合、代谢和消除。合并疾病和对药物作用的敏感性会缩小治疗范围，并使老年患者的药代动力学变得复杂。新型抗惊厥药物的优点可能超过风险，其治疗特性可能有助于治疗这一特殊患者群体。
