Adverse Drug Reactions

About one third of drug-related hospitalizations and one half of drug-related deaths occur in persons > 60. The elderly are at increased risk of toxicity from certain drugs, especially long-acting benzodiazepines, nonsteroidal anti-inflammatory drugs, warfarin, heparin, aminoglycosides, isoniazid, high doses of thiazides, antineoplastic drugs, and most antiarrhythmics (see Table 6-4). Increased risk has not been demonstrated with other drugs (eg, -blockers, antihypertensives, lidocaine, propafenone).

Increased susceptibility may result from age-associated changes in pharmacokinetics or pharmacodynamics or from disorders aggravated by drugs (eg, prostatism by anticholinergic drugs, postural hypotension by diuretics). The risk of an adverse drug reaction increases exponentially with the number of drugs used, in part because polypharmacy reflects the presence of many diseases and provides an opportunity for drug-disease and drug-drug interactions.

Drug-disease interactions (exacerbation of a disease by a drug) can occur in any age group but are especially important in the elderly because of the increased prevalence of disease and the difficulty in differentiating often subtle adverse drug reactions from the effects of disease (see Table 6-5). Anticholinergic drugs are a common cause of such interactions (eg, with glaucoma, benign prostatic hyperplasia, Alzheimer's disease, dry eyes, or xerostomia).

Drug-drug interactions (the altered pharmacokinetics or pharmacodynamics of a drug when taken concomitantly with one or more other drugs) are myriad (see Table 6-6). Few prospective studies of drug-drug interactions in the elderly have been conducted. One study showed that 40% of ambulatory elderly patients were at risk of drug-drug interactions; 27% of these interactions were potentially serious (eg, quinidine-digoxin interaction). Inhibition of one drug's metabolism by another does not appear to change with age; eg, cimetidine and ciprofloxacin inhibit the metabolic rate of theophylline by about 30% in older and younger healthy persons. Aging's effect on induction of drug metabolism varies; eg, induction of theophylline metabolism by phenytoin is similar in older and younger persons, whereas induction of drug metabolism by dichloralphenazone, glutethimide, and rifampin may be decreased in older persons.

Concurrent use of drugs with similar toxicities can result in serious adverse reactions in the elderly. For example, concurrent use of anticholinergic drugs, such as antiparkinsonian drugs (eg, benztropine), tricyclic antidepressants (eg, amitriptyline, imipramine), antipsychotics (eg, thioridazine), antiarrhythmics (eg, disopyramide), and OTC antihistamines (eg, diphenhydramine, chlorpheniramine) may cause or worsen dry mouth, gum disease, blurred vision, constipation, urinary retention, and delirium.