Clinical meaning
Polypharmacy (commonly defined as >= 5 concurrent medications) affects over 40% of adults >65 years and is independently associated with adverse drug reactions (ADRs), drug interactions, falls, cognitive decline, hospitalization, and mortality. Age-related pharmacokinetic changes increase drug sensitivity: decreased total body water and lean mass (higher concentrations of hydrophilic drugs like digoxin), increased body fat (prolonged half-life of lipophilic drugs like diazepam), decreased hepatic blood flow and CYP enzyme activity (reduced first-pass metabolism of propranolol, morphine, verapamil), decreased renal function (GFR declines ~1 mL/min/year after 40 - affects clearance of renally-excreted drugs). Pharmacodynamic changes include increased sensitivity to CNS-active medications (benzodiazepines, opioids, anticholinergics), decreased baroreceptor sensitivity (orthostatic hypotension risk with antihypertensives), and reduced homeostatic reserve (less ability to compensate for drug-induced perturbations). The prescribing cascade occurs when an ADR is misidentified as a new medical condition and treated with another medication: NSAID → hypertension → antihypertensive; amlodipine → edema → furosemide; cholinesterase inhibitor → urinary incontinence → oxybutynin (anticholinergic opposing the cholinergic drug). Deprescribing is the systematic process of identifying and discontinuing medications where existing or potential harms outweigh existing or potential benefits, considering patient goals, functional status, life expectancy, values, and preferences.