Chapter 5: Pharmacotherapy Principles in Older Adults

The principles governing pharmacotherapy in older adults require providers to navigate a complex environment involving a growing, frail population with multiple chronic comorbidities. Age-related physiological changes significantly impact how drugs are handled, leading to altered pharmacokinetic (PK) responses across all stages. Specifically, body composition shifts, including decreased lean body mass and total body water coupled with increased fat stores, affect drug distribution, sometimes leading to prolonged half-lives for lipophilic drugs like diazepam. Reduced serum albumin increases the concentration of unbound, active drugs (e.g., warfarin). Hepatic metabolism (Phase I oxidation) and renal clearance (GFR) decline, necessitating careful dosage calculation, often using formulas like Cockcroft-Gault, as serum creatinine alone is unreliable due to reduced muscle mass. Furthermore, pharmacodynamic (PD) changes result in heightened sensitivity to many agents, leading to exaggerated CNS effects (e.g., confusion, fatigue) and increased risk of orthostatic hypotension and subsequent falls from drugs like benzodiazepines, TCAs, and potent analgesics. Polypharmacy—driven by multimorbidity, multiple providers, and patient expectations—is a major contributor to preventable Adverse Drug Reactions (ADRs) and the prescribing cascade. Adherence is often compromised by cost, inconvenient side effects, physical barriers (e.g., arthritic hands), and cognitive impairment. Critically, patients frequently fail to disclose the use of OTC drugs, herbal preparations, alcohol, caffeine, and nicotine, risking serious drug interactions. Guidelines for safe prescribing emphasize "start low, go slow, but get there," continuous medication review, and using resources like the Beers Criteria. Recent quality initiatives like Choosing Wisely highlight the necessity of patient-centered care, including avoiding intensive cancer screening or lipid-lowering drugs in patients with limited life expectancy, ensuring moderate diabetes control instead of tight control (avoiding sliding scale insulin), limiting antibiotic use for asymptomatic bacteriuria, and prioritizing non-pharmacologic interventions, like careful hand-feeding and environmental modifications, over chemical restraints (antipsychotics/benzodiazepines) for Behavioral and Psychological Symptoms of Dementia (BPSD).