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苯二氮卓类药物中毒及戒断

Authors
Howard Greller, MD
Amit Gupta, MD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM
Translators
许树云, 副主任医师

引言

苯二氮卓类药物(Benzodiazepines, BZD)属镇静催眠药，自20世纪60年代起被应用于临床。第一种BZD氯氮卓是在1954年由奥地利科学家Leo Sternbach意外发现。3年后，它以商品名利眠宁作为治疗性药物上市。继氯氮卓之后，1963年地西泮也被批准上市，随后几年多种其他化合物也相继上市。

BZD用于镇静以及对焦虑、癫痫发作、戒断状态、失眠和药物相关激越状态的治疗。BZD通常与其他药物联合用于操作中镇静由于BZD用途较多而被广泛使用，全球有近50种不同的BZD可用。BZD过量的高发生率也反映出该药的广泛使用及可获得性[1,2]。

BZD急性中毒的诊断和处理总结在此。而中毒患者的一般处理方法及涉及到具有镇静性质的其他药物中毒的处理在别处讨论。 (参见“成人药物中毒的一般处理方法”和“成人乙醇中毒”和“成人阿片中毒”和“Gamma hydroxybutyrate (GHB) intoxication”)

药理学和细胞毒性

BZD是含一个苯环和一个七元二氮卓部分的有机碱；具体药物的效力、作用持续时间、代谢活性及消除速率取决于不同的侧链[3]。BZD发挥作用是通过γ-氨基丁酸A(gamma-aminobutyric acid A, GABA-A)受体的调节作用，γ-氨基丁酸(gamma-aminobutyric acid, GABA)是中枢神经系统主要的抑制性神经递质。

GABA-A受体由α、β和γ按照不同组合的五个亚基构成[4-9]。亚基的构成情况决定了不同的外源性物质与受体结合的亲和力。BZD结合于α和γ亚基界面，一旦结合，即锁定GABA-A受体的构象为增加对GABA亲和力的构象。BZD不改变GABA的合成、释放和代谢，而是通过增强与受体的结合而起到抑制作用。结合增加了通过GABA离子通道的氯离子流，导致突触后超极化，并降低引发动作电位的能力。口服BZD引起呼吸抑制的发生率低，似乎与脑干呼吸中枢的结合位点密度低有关[8]。

                  

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Literature review current through: 2017-07 . | This topic last updated: 2016-07-05.
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