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Pharmacokinetics and pharmacodynamics in older adults
With age the way the body handles a drug changes — more fat and less water, lower kidney clearance and part of liver metabolism — and so does the sensitivity of the target (the brain is more sensitive to sedatives and opioids); hence "start low and go slow", and adjust doses to calculated kidney clearance.
Why it matters in the exam
The exam asks why diazepam stays in the body a long time in an older adult (larger volume of distribution because of more fat, and slow oxidative metabolism), why lithium and digoxin levels rise easily (less water and less kidney clearance), and which benzodiazepine is preferred if one is needed at all (lorazepam, oxazepam or temazepam — which undergo only conjugation and not oxidation in the liver).
Recurring points: a low albumin raises the free fraction of phenytoin and warfarin, so a "normal" total phenytoin level may hide toxicity; kidney clearance is calculated by Cockcroft-Gault, not by creatinine alone; nitrofurantoin is avoided when clearance is below 30 mL/min; and the response to beta-blockers and beta-agonists falls, while sensitivity to anticholinergics, benzodiazepines, opioids and warfarin rises.
The exam also asks about interactions through liver enzymes: drugs that inhibit CYP3A4 (clarithromycin, azoles, verapamil, diltiazem) raise the levels of some statins, calcium channel blockers and DOACs, and enzyme inducers (rifampicin, carbamazepine) lower them. So any new antibiotic or drug in an older adult requires a check of the whole list.
Key points
- More fat, less water, less kidney clearance.
- Fat-soluble drugs — long half-life; water-soluble — high levels.
- Oxidative metabolism falls; conjugation is preserved — lorazepam, oxazepam, temazepam.
- Dose by Cockcroft-Gault; not by creatinine alone.
- Increased brain sensitivity; "start low and go slow".
Summary table
| Stage | Change with age | Exam example |
|---|---|---|
| Absorption | Small change, little clinical significance | Usually no adjustment needed |
| Distribution | More fat and less water; lower albumin | Diazepam — long half-life; lithium, digoxin — higher levels; free phenytoin rises |
| Liver metabolism | Oxidative metabolism (phase I) falls; conjugation (phase II) is preserved | Lorazepam, oxazepam, temazepam — conjugation only |
| Kidney excretion | Lower filtration | Adjust dose by Cockcroft-Gault; nitrofurantoin — not below 30 mL/min |
| Pharmacodynamics | Increased brain sensitivity; reduced beta-receptor response | More confusion from benzodiazepines and opioids; less response to beta-blockers |
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Sources
- Hazzard's Geriatric Medicine and Gerontology, 8th edition (2022) — Pharmacotherapy and age-related changes in pharmacokinetics and pharmacodynamics
- Geriatrics Review Syllabus (American Geriatrics Society), 11th edition (2022) — Pharmacotherapy
- American Geriatrics Society Beers Criteria, 2023 update — Drugs to adjust for kidney function
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.