Pharmacological changes in ageing patients

Overview

Ageing alters both pharmacokinetics (what the body does to a drug) and pharmacodynamics (what the drug does to the body), together explaining why standard adult doses often need adjustment in older patients
Nearly universal to some degree by advanced old age, and compounded further by comorbidity (particularly renal/hepatic impairment) common in this population

Pharmacokinetic changes: reduced lean body mass and increased fat mass (prolongs the half-life of fat-soluble drugs, e.g. benzodiazepines), reduced hepatic blood flow/first-pass metabolism, and progressively reduced renal clearance - all tending to increase drug exposure/accumulation at a standard adult dose
Pharmacodynamic changes: increased end-organ sensitivity to many drug classes even at unchanged plasma concentration - particularly sedatives, anticholinergics, antihypertensives, and drugs affecting postural blood pressure control

No single test diagnoses these changes directly - they are inferred from age, renal/hepatic function testing, and clinical response, and anticipated proactively in prescribing rather than discovered only after an adverse reaction occurs

"Start low, go slow" - lower starting doses and slower up-titration than in younger adults, given both the pharmacokinetic tendency to accumulate and the pharmacodynamic tendency toward increased sensitivity
Renal dose adjustment should use an appropriate estimate of renal function (not assume normal clearance) for any renally-cleared drug
Regularly reassess ongoing need and dose as renal/hepatic function and body composition can continue to change over time, not just at initiation

Polypharmacy, adverse drug reactions, falls (from postural hypotension/sedation), delirium (from anticholinergic/sedative burden)
The combination of pharmacokinetic accumulation and pharmacodynamic hypersensitivity means the same standard adult dose can produce a materially larger and more prolonged effect in an older patient than in a younger one - this is a combined, not single, mechanism and explains why simple linear dose-scaling by weight is often insufficient

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