10.5 Geriatric Pharmacology
Aging affects drug pharmacokinetics and pharmacodynamics, increasing risk of adverse effects and drug interactions. Polypharmacy management is essential in elderly patients.
Age-Related Pharmacokinetic Changes
Absorption
- • ↑ Gastric pH, ↓ GI motility
- • ↓ Splanchnic blood flow
- • Usually minimal clinical impact
Distribution
- • ↓ Total body water (60% → 50%)
- • ↑ Body fat (18% → 36%)
- • ↓ Lean body mass
- • ↓ Albumin → ↑ free drug (highly protein-bound drugs)
- • ↑ Vd for lipophilic drugs (prolonged half-life)
Metabolism
- • ↓ Hepatic blood flow (40% decrease)
- • ↓ Hepatic mass
- • ↓ Phase I metabolism (CYP450) > Phase II
- • ↓ First-pass effect → ↑ bioavailability
- • Reduced clearance of many drugs
Excretion
- • ↓ Renal mass, blood flow, GFR
- • GFR declines ~1 mL/min/year after age 40
- • Use Cockcroft-Gault or CKD-EPI for dosing
- • Dose adjustment for renally cleared drugs
Pharmacodynamic Changes
↑ Sensitivity
- • CNS drugs: Benzodiazepines, opioids, anticholinergics
- • Anticoagulants: Warfarin (same dose → ↑ INR)
- • Cardiovascular: β-blockers, antihypertensives
- • Higher risk of delirium, falls, confusion
↓ Sensitivity
- • β-agonists: ↓ Bronchodilation (↓ receptor density)
- • β-blockers: ↓ Cardiac response
- • Baroreceptor reflex impaired → orthostatic hypotension
Beers Criteria (Potentially Inappropriate Medications)
⚠️ High-Risk Drugs in Elderly
Anticholinergics
- • Diphenhydramine, hydroxyzine (first-gen antihistamines)
- • Tricyclic antidepressants
- • Risks: Confusion, delirium, falls, urinary retention, constipation
Benzodiazepines
- • All benzodiazepines (especially long-acting: diazepam)
- • Risks: Cognitive impairment, falls, hip fractures
- • Prefer short-acting if necessary (lorazepam)
Sedative-Hypnotics
- • Zolpidem, eszopiclone (Z-drugs)
- • Risks: Falls, fractures, confusion
NSAIDs
- • Chronic use of any NSAID (including COX-2 inhibitors)
- • Risks: GI bleeding, renal impairment, HTN, HF
- • Prefer acetaminophen for chronic pain
Other High-Risk
- • Sulfonylureas (long-acting): Glyburide (hypoglycemia risk)
- • Muscle relaxants: Cyclobenzaprine, methocarbamol
- • Antipsychotics: Avoid in dementia (↑ mortality, stroke)
- • Digoxin: Doses >0.125 mg/day (narrow therapeutic index)
Polypharmacy Management
Polypharmacy (≥5 medications) affects >40% of elderly patients, increasing risk of adverse drug reactions, drug interactions, and non-adherence.
Strategies
- • Regular medication reconciliation
- • Deprescribing non-essential drugs
- • "Start low, go slow" dosing
- • Simplify regimens (reduce pill burden)
- • Monitor for drug-drug interactions
Adverse Event Prevention
- • Assess renal function (adjust doses)
- • Review Beers Criteria annually
- • Monitor for falls, cognitive changes
- • Educate on proper medication use
- • Consider pill organizers, alarms