Clinical meaning
Polypharmacy (use of 5 or more concurrent medications) affects over 40% of adults aged 65 and older and is a geriatric syndrome in its own right because the physiological consequences extend beyond individual drug effects. Each additional medication increases adverse drug event risk by approximately 10%, and medications cause an estimated 30% of geriatric syndromes including falls, delirium, incontinence, and anorexia. The aging body processes drugs differently at every pharmacokinetic step: gastric pH rises (reducing absorption of drugs requiring acid dissolution), decreased albumin and increased alpha-1 acid glycoprotein alter protein binding of acidic and basic drugs respectively, hepatic blood flow drops 30-40% (decreasing first-pass metabolism and increasing bioavailability of high-extraction drugs such as morphine, propranolol, and verapamil), and fat-to-lean mass ratio increases (extending half-life of lipophilic drugs like diazepam and amiodarone while concentrating hydrophilic drugs like digoxin and lithium in reduced total body water). Pharmacodynamically, age-related receptor changes amplify drug effects: decreased baroreceptor sensitivity increases orthostatic hypotension risk with antihypertensives, reduced cholinergic reserve magnifies anticholinergic toxicity, and blood-brain barrier permeability changes enhance CNS drug penetration. The prescribing cascade — where a drug side effect is misinterpreted as a new condition warranting additional therapy — perpetuates medication accumulation. Every new symptom in an older adult should first be evaluated as a potential adverse drug effect before adding another medication to the regimen.