Iivanainen M
Department of Child Neurology, University of Helsinki, Finland.
J Intellect Disabil Res. 1998 Dec;42 Suppl 1:24-31.
Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half-life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs.
苯妥英（5,5-二苯基乙内酰脲）已使用60年，至今仍是一种重要的抗癫痫药物。其主要作用机制是通过直接抑制和阻断神经元细胞膜上的电压门控钠通道以及延迟细胞再激活来调节神经元的持续重复放电。苯妥英的血浆蛋白结合率通常在90%至95%之间。该药从血液迅速分布到组织中，并几乎完全在肝脏代谢。血浆苯妥英浓度通常在1至2周内达到稳态水平。苯妥英低剂量时半衰期小于20小时，但高剂量时、新生儿及老年人中半衰期会延长。当苯妥英与酶诱导药物如苯巴比妥或卡马西平同时使用时，半衰期会缩短。苯妥英对治疗全身性强直阵挛性发作、伴有或不伴有泛化的部分性发作以及惊厥性癫痫持续状态有效。多年来，人们已经认识到苯妥英许多新的甚至严重的不良反应。苯妥英脑病表现为认知障碍和小脑综合征，是一种重要的不良神经效应，其发生取决于苯妥英的饱和动力学、苯妥英代谢的个体差异、某些药物对苯妥英代谢的抑制作用或某些药物将苯妥英从血浆蛋白上置换下来的能力，从而导致游离苯妥英血浆水平升高。由于其潜在的不良反应，除作为治疗惊厥性癫痫持续状态的联合用药外，苯妥英不推荐作为治疗癫痫发作的首选药物。对于同时患有智力残疾且易发生平衡障碍和认知功能障碍的癫痫患者，明智的做法是用另一种药物如卡马西平或奥卡西平替代苯妥英。对于行动不便、有明显认知障碍或有小脑疾病症状体征的患者，不建议长期使用苯妥英。预防苯妥英中毒及随后发生的苯妥英诱导的脑病，依赖于对患者的仔细观察以及频繁监测苯妥英和其他同时使用的抗癫痫药物的血浆水平。
