Meier P J, Ziegler W H, Neftel K
Departement für Innere Medizin, Universitätsspital, Zürich.
Schweiz Med Wochenschr. 1988 Mar 19;118(11):381-92.
Benzodiazepines are the most frequently prescribed drugs in the Western world. About 3% of the adult Swiss population regularly use benzodiazepines for the treatment of anxiety states or for induction of sleep. All benzodiazepine agonists available exert qualitatively similar pharmacodynamic actions. They commonly activate central GABAergic neuroinhibition, thereby inducing anxiolysis, sedation/hypnosis, anticonvulsion and muscle relaxation. However, various derivatives differ in their physicochemical and pharmacokinetic properties such as lipophilicity, rate of gastrointestinal absorption, hepatic biotransformation and elimination half life. These differences among individual substances can be used clinically to optimize therapy for the individual patient. For example, the elimination half life greatly influences the frequency, intensity and type of adverse reactions such as hangover, rebound insomnia, development of tolerance and dependence as well as withdrawal symptoms. It is estimated that "low-dose dependency" develops in as many as 30 to 45% of chronically treated patients. Low-dose dependency is mainly characterized by the appearance of withdrawal symptoms after cessation of therapy. Since management of the withdrawal state is difficult and especially troublesome for the patient it is best to prevent the development of benzodiazepine dependence by prescribing these drugs less and restricting them to short-term use (7-14 days).
苯二氮䓬类药物是西方世界最常被处方的药物。约3%的瑞士成年人口经常使用苯二氮䓬类药物来治疗焦虑状态或诱导睡眠。所有可用的苯二氮䓬类激动剂在药效学作用上具有定性相似性。它们通常激活中枢γ-氨基丁酸能神经抑制，从而产生抗焦虑、镇静/催眠、抗惊厥和肌肉松弛作用。然而，各种衍生物在其物理化学和药代动力学性质方面存在差异，如亲脂性、胃肠道吸收速率、肝脏生物转化和消除半衰期。个体物质之间的这些差异可在临床上用于优化个体患者的治疗。例如，消除半衰期极大地影响不良反应的频率、强度和类型，如宿醉、反弹性失眠、耐受性和依赖性的发展以及戒断症状。据估计，在多达30%至45%的长期治疗患者中会出现“低剂量依赖性”。低剂量依赖性主要表现为治疗停止后出现戒断症状。由于戒断状态的管理困难且对患者尤其麻烦，最好通过减少这些药物的处方并将其限制在短期使用（7 - 14天）来预防苯二氮䓬类药物依赖性的发展。
