Moore A R, O'Keeffe S T
Department of Geriatric Medicine, St. Vincent's Hospital, Dublin, Ireland.
Drugs Aging. 1999 Jul;15(1):15-28. doi: 10.2165/00002512-199915010-00002.
Elderly people are more likely than younger patients to develop cognitive impairment as a result of taking medications. This reflects age- and disease-associated changes in brain neurochemistry and drug handling. Delirium (acute confusional state) is the cognitive disturbance most clearly associated with drug toxicity, but dementia has also been reported. The aetiology of cognitive impairment is commonly multifactorial, and it may be difficult to firmly establish a causal role for an individual medication. In studies of elderly hospital patients, drugs have been reported as the cause of delirium in 11 to 30% of cases. Medication toxicity occurs in 2 to 12% of patients presenting with suspected dementia. In some cases CNS toxicity occurs in a dose-dependent manner, often as a result of interference with neurotransmitter function. Drug-induced delirium can also occur as an idiosyncratic complication. Finally, delirium may occur secondary to iatrogenic complications of drug use. Almost any drug can cause delirium, especially in a vulnerable patient. Impaired cholinergic neurotransmission has been implicated in the pathogenesis of delirium and of Alzheimer's disease. Anticholinergic medications are important causes of acute and chronic confusional states. Nevertheless, polypharmacy with anticholinergic compounds is common, especially in nursing home residents. Recent studies have suggested that the total burden of anticholinergic drugs may determine development of delirium rather than any single agent. Also, anticholinergic effects have been identified in many drugs other than those classically thought of as having major anticholinergic effects. Psychoactive drugs are important causes of delirium. Narcotic agents are among the most important causes of delirium in postoperative patients. Long-acting benzodiazepines are the commonest drugs to cause or exacerbate dementia. Delirium was a major complication of treatment with tricyclic antidepressants but seems less common with newer agents. Anticonvulsants can cause delirium and dementia. Drug-induced confusion with nonpsychoactive drugs is often idiosyncratic in nature, and the diagnosis is easily missed unless clinicians maintain a high index of suspicion. Histamine H2 receptor antagonists, cardiac medications such as digoxin and beta-blockers, corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all cause acute, and, less commonly, chronic confusion. Drug-induced confusion can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow'. Special care is needed when prescribing for people with cognitive impairment. Early diagnosis of drug-induced confusion, and withdrawal of the offending agent or agents is essential.
与年轻患者相比,老年人因服药更易出现认知障碍。这反映了大脑神经化学和药物处理方面与年龄及疾病相关的变化。谵妄(急性意识模糊状态)是与药物毒性最明显相关的认知障碍,但也有痴呆的报道。认知障碍的病因通常是多因素的,可能难以确切确定某一种药物的因果作用。在老年住院患者的研究中,据报道药物是11%至30%病例中谵妄的病因。在疑似痴呆的患者中,2%至12%会出现药物毒性。在某些情况下,中枢神经系统毒性呈剂量依赖性发生,通常是由于干扰神经递质功能所致。药物性谵妄也可能作为一种特异质性并发症出现。最后,谵妄可能继发于药物使用的医源性并发症。几乎任何药物都可导致谵妄,尤其是在易感患者中。胆碱能神经传递受损与谵妄和阿尔茨海默病的发病机制有关。抗胆碱能药物是急性和慢性意识模糊状态的重要病因。然而,使用抗胆碱能化合物的联合用药很常见,尤其是在养老院居民中。最近的研究表明,抗胆碱能药物的总负担可能决定谵妄的发生,而非任何单一药物。此外,在许多并非传统上认为具有主要抗胆碱能作用的药物中也发现了抗胆碱能效应。精神活性药物是谵妄的重要病因。麻醉剂是术后患者谵妄的最重要病因之一。长效苯二氮䓬类药物是导致或加重痴呆最常见的药物。谵妄是三环类抗抑郁药治疗的主要并发症,但在新型药物中似乎较少见。抗惊厥药可导致谵妄和痴呆。非精神活性药物引起的药物性意识模糊通常具有特异质性,除非临床医生保持高度怀疑指数,否则很容易漏诊。组胺H2受体拮抗剂、地高辛和β受体阻滞剂等心脏药物、皮质类固醇、非甾体抗炎药和抗生素都可导致急性意识模糊,较少导致慢性意识模糊。通过避免联合用药并遵循“从小剂量开始,缓慢增加剂量”的原则,可预防药物性意识模糊。为认知障碍患者开处方时需要特别小心。早期诊断药物性意识模糊并停用致病药物至关重要。