Pathophysiology
Clinical meaning
The American Geriatrics Society (AGS) Beers Criteria is an evidence-based list of potentially inappropriate medications (PIMs) for older adults aged 65 and older. The criteria address medications that pose disproportionate risks in geriatric patients due to age-related physiological changes in drug handling. Age-related pharmacokinetic changes fundamentally alter drug disposition. Decreased gastric acid production and reduced GI motility can alter absorption of pH-dependent drugs. Decreased total body water (by 10-15%) and increased adiposity increase the volume of distribution for lipophilic drugs (benzodiazepines, amitriptyline), prolonging their half-lives and duration of action. Decreased serum albumin (common in frail elderly) increases the free fraction of highly protein-bound drugs (warfarin, phenytoin), intensifying their effects. Hepatic metabolism declines due to reduced liver mass (by 20-30%) and decreased hepatic blood flow, particularly affecting Phase I (CYP450) oxidative metabolism while Phase II conjugation reactions are relatively preserved. Renal elimination decreases as GFR declines approximately 1 mL/min/year after age 40, requiring dose adjustment for renally cleared drugs. Pharmacodynamic changes include increased sensitivity to CNS depressants (benzodiazepines, opioids, anticholinergics) due to decreased cholinergic neurotransmission, reduced dopaminergic tone, and blood-brain barrier...