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常用药物的抗胆碱能活性与老年人的神经精神不良事件

Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people.

作者信息

Nishtala Prasad S, Fois Romano A, McLachlan Andrew J, Bell J Simon, Kelly Patrick J, Chen Timothy F

机构信息

Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.

出版信息

J Clin Pharmacol. 2009 Oct;49(10):1176-84. doi: 10.1177/0091270009345690.

Abstract

This study sought to determine whether the presence of in vitro anticholinergic activity (AA) among different drugs is associated with reporting of neuropsychiatric adverse events (NPAEs) and whether age affects this relationship. Retrospective case/noncase analyses using Australia's spontaneous Adverse Drug Reaction System (ADRS) database containing 150 475 reports determined crude and adjusted reporting odds ratios (RORs) for NPAEs for 23 drugs with various reported in vitro AA. Covariates were age (treated as a dichotomous variable [> or =65 years]), gender, and concomitant use of antipsychotics, benzodiazepines, tricyclic antidepressants, and drugs with recognized inherent anticholinergic properties (anticholinergic drugs). The interaction effect between these covariates and each drug exposure category was examined. Age (> or =65 years) has a significant association with greater odds relative to younger age for reporting NPAEs. Drugs with reported significant AA in vitro were not always associated with RORs greater than 1 for reporting NPAEs, highlighting a dissonance between the in vitro AA index and ADRS observations. Significant interactions were observed between age (> or =65 years) and exposure to cimetidine, anticholinergic drugs, antipsychotics, and tricyclic antidepressants in modifying odds for reporting NPAEs, reinforcing the need for cautious use and monitoring of drugs with AA in older people.

摘要

本研究旨在确定不同药物的体外抗胆碱能活性(AA)是否与神经精神不良事件(NPAE)的报告相关,以及年龄是否会影响这种关系。利用澳大利亚自发药物不良反应系统(ADRS)数据库进行回顾性病例/非病例分析,该数据库包含150475份报告,确定了23种报告有不同体外AA的药物发生NPAE的粗报告比值比(ROR)和校正报告比值比。协变量包括年龄(作为二分变量[≥65岁])、性别,以及同时使用抗精神病药、苯二氮卓类药物、三环类抗抑郁药和具有公认固有抗胆碱能特性的药物(抗胆碱能药物)。研究了这些协变量与每种药物暴露类别之间的交互作用。年龄(≥65岁)与报告NPAE的较高比值比显著相关,相对于年轻年龄组。报告有显著体外AA的药物在报告NPAE时并不总是与大于1的ROR相关,这突出了体外AA指数与ADRS观察结果之间的不一致。在年龄(≥65岁)与西咪替丁、抗胆碱能药物、抗精神病药和三环类抗抑郁药的暴露之间观察到显著的交互作用,这些交互作用改变了报告NPAE的比值比,这进一步强调了在老年人中谨慎使用和监测具有AA的药物的必要性。

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