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Intranasal delivery of antiepileptic medications for treatment of seizures.
Neurotherapeutics ( IF 5.7 ) Pub Date : 2009 , DOI: 10.1016/j.nurt.2009.01.002
Daniel P Wermeling 1
Affiliation  

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 care-givers 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.

中文翻译:

用于治疗癫痫发作的抗癫痫药物的鼻内给药。

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都被视为医疗紧急情况。死亡率和更糟的神经系统结果与癫痫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、机构和家庭环境中癫痫发作的药物治疗方案的共识声明。苯二氮卓类药物,例如劳拉西泮、地西泮、咪达唑仑和氯硝西泮被认为是首选药物。药物输送到全身循环然后输送到大脑的速度在减少治疗癫痫发作所需的时间和减少对中枢神经系统造成损害的机会方面发挥着重要作用。分娩速度,尤其是在医院外,当使用经粘膜递送途径代替静脉注射时,苯二氮卓类药物的鼻内经粘膜递送可用于在院前环境中减少给药时间和停止癫痫发作,当积极抓住患者到达急诊室时,和在家中,护理人员在那里治疗他们的家属。本综述总结了选择苯二氮卓类药物鼻内给药时要考虑的因素,包括配方和设备考虑因素、药理学和药代动力学/药效学特征。对癫痫患者最相关临床研究的回顾将为这种技术与许多苯二氮卓类药物和相对不太复杂的鼻腔制剂的相对成功提供背景。鼻内递送的神经肽,通过嗅觉系统穿过血脑屏障,可能会增加治疗癫痫的药物的可用性。因此,通过鼻内抗癫痫药产品的商业开发和营销来满足癫痫患者的药物治疗需求,仍然存在显着未满足的医疗需求。
更新日期:2020-09-23
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