Potential Adverse Effects of Bronchodilators in the Treatment of Airways Obstruction in Older People: Recommendations for Prescribing

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.