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支气管扩张剂治疗老年人气道阻塞的潜在不良反应:处方建议

Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing.

作者信息

Gupta Preeti, O'Mahony M Sinead

机构信息

University Department of Geriatric Medicine, Academic Centre, Llandough Hospital, Cardiff, UK.

出版信息

Drugs Aging. 2008;25(5):415-43. doi: 10.2165/00002512-200825050-00005.

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are common disorders that are associated with increasing morbidity and mortality in older people. Bronchodilators are used widely in patients with these conditions, but even when used in inhaled form can have systemic as well as local effects. Older people experience more adverse drug effects because of pharmacodynamic and pharmacokinetic changes and particularly drug-drug and drug-disease interactions. Cardiovascular disease is common in older people and beta-adrenoceptor agonists (beta-agonists) have inotropic and chronotropic effects that can increase arrhythmias and cardiomyopathy. They can also worsen or induce myocardial ischaemia and cause electrolyte disturbances that contribute to arrhythmias. Tremor is a well known distressing adverse effect of beta-agonist administration. Long-term beta-agonist use can be associated with tolerance, poor disease control, sudden life-threatening exacerbations and asthma-related deaths. Functional beta2-adrenoceptors are present in osteoblasts, and chronic use of beta-agonists has been implicated in osteoporosis. Inhaled anticholinergics are usually well tolerated but may cause dry mouth, which can be troublesome in older people. Pupillary dilatation, blurred vision and acute glaucoma can occur from escape of droplets from loosely fitting nebulizer masks. Although ECG changes have not been seen in randomized controlled trials of long-acting inhaled anticholinergics, supraventricular tachycardias have been observed in a 5-year randomized controlled trial of ipratropium bromide. Paradoxical bronchoconstriction can occur with inhaled anticholinergics as well as with beta-agonists, but tolerance has not been reported with anticholinergics. Anticholinergic drugs also cause central effects, most notably impairment of cognitive function, and these effects have been noted with inhaled agents. Use of theophylline is limited by its adverse effects, which range from commonly occurring gastrointestinal symptoms to palpitations, arrhythmias and reports of myocardial infarction. Seizures have been reported, but are rare. Theophylline is metabolized primarily by the liver, and commonly interacts with other medications. Its concentration in plasma should be monitored closely, especially in older people. Although many clinical trials have been conducted on bronchodilators in obstructive airways disease, the results of these clinical trials need to be interpreted with caution as older people are often under-represented and subjects with co-morbidities actively excluded from these trials.

摘要

哮喘和慢性阻塞性肺疾病(COPD)是常见疾病,在老年人中发病率和死亡率呈上升趋势。支气管扩张剂在患有这些疾病的患者中广泛使用,但即使以吸入形式使用,也会产生全身和局部影响。由于药效学和药代动力学变化,尤其是药物 - 药物和药物 - 疾病相互作用,老年人更容易出现药物不良反应。心血管疾病在老年人中很常见,β - 肾上腺素能受体激动剂(β - 激动剂)具有变力性和变时性作用,可增加心律失常和心肌病的发生风险。它们还可加重或诱发心肌缺血,并导致电解质紊乱,进而引发心律失常。震颤是β - 激动剂给药众所周知的令人苦恼的不良反应。长期使用β - 激动剂可能会导致耐受性、疾病控制不佳、危及生命的突然加重以及与哮喘相关的死亡。成骨细胞中存在功能性β2 - 肾上腺素能受体,长期使用β - 激动剂与骨质疏松症有关。吸入性抗胆碱能药物通常耐受性良好,但可能会导致口干,这在老年人中可能会造成困扰。雾化面罩佩戴不紧导致的药物液滴泄漏可引起瞳孔散大、视力模糊和急性青光眼。尽管在长效吸入性抗胆碱能药物的随机对照试验中未观察到心电图变化,但在一项为期5年的异丙托溴铵随机对照试验中观察到了室上性心动过速。吸入性抗胆碱能药物以及β - 激动剂都可能发生矛盾性支气管收缩,但抗胆碱能药物尚未有耐受性的报道。抗胆碱能药物还会产生中枢作用,最显著的是认知功能损害,吸入剂也有这些作用。茶碱的使用受到其不良反应的限制,不良反应范围从常见的胃肠道症状到心悸、心律失常以及心肌梗死的报告。曾有癫痫发作的报道,但很罕见。茶碱主要在肝脏代谢,通常与其他药物相互作用。应密切监测其血浆浓度,尤其是在老年人中。尽管针对阻塞性气道疾病中的支气管扩张剂进行了许多临床试验,但这些临床试验的结果需要谨慎解读,因为老年人在试验中往往代表性不足,患有合并症的受试者通常被主动排除在这些试验之外。

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