Wermeling Daniel P
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0082, USA.
Neurotherapeutics. 2009 Apr;6(2):352-8. doi: 10.1016/j.nurt.2009.01.002.
Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital, institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures in the pre-hospital setting, when actively seizing patients arrive in the emergency room, and at home where caregivers treat their dependents. This review summarizes factors to consider when choosing a benzodiazepine for intranasal administration, including formulation and device considerations, pharmacology and pharmacokinetic/pharmacodynamic profiles. A review of the most relevant clinical studies in epilepsy patients will provide context for the relative success of this technique with a number of benzodiazepines and relatively less sophisticated nasal preparations. Neuropeptides delivered intranasally, crossing the blood-brain barrier via the olfactory system, may increase the availability of medications for treatment of epilepsy. Consequently, there remains a significant unmet medical need to serve the pharamcotherapeutic requirements of epilepsy patients through commercial development and marketing of intranasal antiepileptic products.
急性孤立性癫痫发作、重复性或复发性癫痫发作以及癫痫持续状态均被视为医疗急症。死亡率和更差的神经学转归与癫痫发作活动的持续时间直接相关。最近的一些综述描述了关于患者在院前、机构和居家环境中癫痫发作的药物治疗方案的共识声明。苯二氮䓬类药物，如劳拉西泮、地西泮、咪达唑仑和氯硝西泮被认为是首选药物。一种药物能够输送到体循环然后到达大脑的速度在减少治疗癫痫发作所需时间以及减少对中枢神经系统造成损害的机会方面起着重要作用。当使用经粘膜给药途径代替静脉注射时，尤其是在院外，药物输送速度会加快。苯二氮䓬类药物的鼻内粘膜给药在减少院前环境中癫痫发作患者到达急诊室时以及在家中护理人员治疗其家属时的给药时间和癫痫发作停止时间方面是有用的。本综述总结了选择用于鼻内给药的苯二氮䓬类药物时需要考虑的因素，包括制剂和装置方面的考虑、药理学以及药代动力学/药效学特征。对癫痫患者最相关的临床研究进行综述将为该技术使用多种苯二氮䓬类药物和相对不太复杂的鼻腔制剂的相对成功提供背景信息。经鼻内递送的神经肽通过嗅觉系统穿过血脑屏障，可能会增加用于治疗癫痫的药物的可及性。因此，通过鼻内抗癫痫产品的商业开发和营销来满足癫痫患者的药物治疗需求仍存在重大未满足的医疗需求。
