Sears Malcolm R
Firestone Institute for Respiratory Health, St Joseph's Healthcare and Master University, Hamilton, Ontario, Canada.
J Allergy Clin Immunol. 2002 Dec;110(6 Suppl):S322-8. doi: 10.1067/mai.2002.129966.
Short-acting beta-adrenergic receptor agonists have pharmacologically predictable dose-related and potency-related adverse effects, including tachycardia and tremor, and they also affect serum potassium and glucose. These effects all show tolerance with continued exposure. The potential for arrhythmia is increased by comorbidity and hypoxemia. Nonpharmacologically predictable effects include airway hyperresponsiveness to nonspecific and specific stimuli, including allergen and exercise, and increased airway inflammation. Genetic variants of the beta-adrenergic receptor alter susceptibility to adverse effects of beta-agonists on airway function. The impact of the enantiomers of beta-agonists on adverse effects remains unclear. The two epidemics of asthma death among young people were temporally associated with introduction of potent short-acting beta-agonists (isoproterenol and fenoterol) and appear to be related to adverse effects of these drugs on airway function and airway hyperresponsiveness rather than to cardiotoxicity. Compared with short-acting agents, long-acting beta-agonists show similar but less pronounced pharmacologically predictable effects, and they have not been shown to increase airway hyperresponsiveness in adults. Postmarketing surveillance studies have not suggested significant adverse effects of long-acting beta-agonists on morbidity and mortality.
短效β-肾上腺素能受体激动剂具有药理学上可预测的剂量相关和效能相关的不良反应,包括心动过速和震颤,并且它们还会影响血清钾和血糖。持续用药后,这些效应都会出现耐受性。合并症和低氧血症会增加心律失常的风险。非药理学可预测的效应包括气道对非特异性和特异性刺激(包括过敏原和运动)的高反应性以及气道炎症增加。β-肾上腺素能受体的基因变异会改变β-激动剂对气道功能不良反应的易感性。β-激动剂对映体对不良反应的影响尚不清楚。年轻人中发生的两起哮喘死亡流行在时间上与强效短效β-激动剂(异丙肾上腺素和非诺特罗)的引入有关,并且似乎与这些药物对气道功能和气道高反应性的不良反应有关,而非心脏毒性。与短效药物相比,长效β-激动剂显示出相似但不太明显的药理学可预测效应,并且尚未证明它们会增加成人的气道高反应性。上市后监测研究未提示长效β-激动剂对发病率和死亡率有显著不良反应。