Treiman D M
Neurology Service, Veterans Administration, West Los Angeles Medical Center.
Epilepsia. 1989;30 Suppl 2:S4-10. doi: 10.1111/j.1528-1157.1989.tb05824.x.
Benzodiazepines are potent and effective drugs for the management of acute seizures and status epilepticus. Lorazepam, diazepam, and clonazepam have been the most widely studied of the benzodiazepines in the treatment of status epilepticus. In 47 studies of these drugs involving 1,455 patients, lasting control of status epilepticus was achieved in 79% of the patients. None of these benzodiazepines is clearly superior to another for the effective control of status epilepticus. Differences in pharmacokinetic parameters, therefore, will influence the choice of drug. All three benzodiazepines are lipid-soluble and enter the brain within seconds to minutes after intravenous administration. Diazepam, however, is very lipid-soluble and highly protein-bound and thus has a very large volume of distribution of unbound drug. As a result, the effective duration of action of diazepam in status epilepticus is only 20 to 30 min, whereas that of lorazepam, which has a much smaller volume of distribution of unbound drug, is at least several hours after a single intravenous injection. This allows the orderly administration of an antiepileptic drug for long-term seizure control after status epilepticus has been controlled. For this reason, lorazepam is preferable for the initial management of status epilepticus. Continuous intravenous infusion of diazepam has been used successfully in the management of some patients with status epilepticus refractory to initial treatment.
苯二氮䓬类药物是治疗急性惊厥和癫痫持续状态的有效强效药物。在治疗癫痫持续状态方面，劳拉西泮、地西泮和氯硝西泮是苯二氮䓬类药物中研究最为广泛的。在47项涉及1455例患者的关于这些药物的研究中，79%的患者实现了癫痫持续状态的持久控制。在有效控制癫痫持续状态方面，这些苯二氮䓬类药物中没有一种明显优于另一种。因此，药代动力学参数的差异将影响药物的选择。所有这三种苯二氮䓬类药物都是脂溶性的，静脉给药后几秒钟到几分钟内即可进入大脑。然而，地西泮脂溶性非常高且蛋白结合率高，因此未结合药物的分布容积非常大。结果，地西泮在癫痫持续状态中的有效作用持续时间仅为20至30分钟，而未结合药物分布容积小得多的劳拉西泮，单次静脉注射后的作用持续时间至少为几个小时。这使得在癫痫持续状态得到控制后，可以有序地给予抗癫痫药物以进行长期的癫痫控制。因此，劳拉西泮更适合用于癫痫持续状态的初始治疗。持续静脉输注地西泮已成功用于治疗一些对初始治疗难治的癫痫持续状态患者。
