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...