Clinical meaning
Deprescribing is the planned, supervised process of dose reduction or discontinuation of medications that are no longer needed, have risks outweighing benefits, or contribute to polypharmacy-related harm. It is a critical component of rational pharmacotherapy, particularly in elderly patients where polypharmacy (≥5 medications) affects 40-50% of those over 65 years. The pharmacological rationale for deprescribing centers on age-related pharmacokinetic and pharmacodynamic changes that alter drug behavior. Aging reduces hepatic blood flow by 20-40% and decreases Phase I metabolism (CYP450 oxidation, reduction, hydrolysis), prolonging the half-life of drugs metabolized by these pathways (benzodiazepines, warfarin, calcium channel blockers). Phase II metabolism (conjugation) is relatively preserved. Renal clearance declines with age (GFR decreases ~1 mL/min/year after age 40), requiring dose adjustment for renally cleared drugs. Increased body fat percentage increases the volume of distribution for lipophilic drugs (diazepam, amiodarone), prolonging their effects. Decreased serum albumin increases the free fraction of highly protein-bound drugs, intensifying their effects. Pharmacodynamically, elderly patients have increased receptor sensitivity to CNS-active drugs (benzodiazepines, opioids, anticholinergics), reduced baroreceptor sensitivity (increased orthostatic hypotension with antihypertensives), and impaired homeostatic mechanisms. The prescribing...