Polypharmacy in Older Adults
Adults over 65 take an average of 4–7 regular medications; many take 10 or more. Ageing fundamentally changes how drugs are handled and tolerated. This guide covers the pharmacokinetic consequences of ageing, how to identify inappropriate medications with the Beers Criteria, deprescribing strategies, and managing interactions in complex regimens.
How ageing changes pharmacokinetics
All four phases of pharmacokinetics are affected by ageing, often in ways that increase drug exposure and duration of action:
Largely unchanged. Gastric pH rises (atrophic gastritis); GI motility slows. Most oral drugs still well absorbed. Transdermal absorption may increase with thinner skin.
Fat mass increases (↑Vd for lipophilic drugs, prolonging t½). Total body water decreases (↓Vd for hydrophilic drugs → higher Cmax). Albumin falls → ↑free fraction of highly protein-bound drugs (warfarin, phenytoin, NSAIDs). See protein binding.
Liver mass and hepatic blood flow fall 20–40% by age 80. Phase I (CYP) clearance reduced; Phase II (conjugation) relatively preserved. High-extraction drugs (lidocaine, morphine, propranolol) most affected. See extraction ratio.
GFR declines ~1 mL/min/year from age 40. Serum creatinine may appear normal despite reduced GFR (less muscle mass → less creatinine production). Use CKD-EPI or Cockcroft-Gault. Renally cleared drugs accumulate. See renal dosing guide.
The net result: older patients require lower starting doses, longer titration intervals, and more frequent monitoring than younger adults. Start low, go slow is the guiding principle. Pharmacokinetic background: PK basics, clearance, volume of distribution, half-life.
Beers Criteria: potentially inappropriate medications
The AGS Beers Criteria ↗ (updated 2023) lists medications that are generally inappropriate in adults ≥65 years — either because of high adverse effect risk, poor efficacy evidence in older adults, or safer alternatives being available. Major categories:
| Drug / class | Risk in older adults | Preferred alternative |
|---|---|---|
| Diphenhydramine (OTC sleep aids) | Anticholinergic: confusion, falls, urinary retention, delirium | Short-term low-dose melatonin; sleep hygiene |
| Benzodiazepines (all) | Falls, fractures, cognitive impairment, paradoxical agitation | CBT-I for insomnia; non-benzo anxiolytics |
| Non-selective NSAIDs (oral) | GI bleed (↑ with anticoagulants), AKI, fluid retention, hypertension | Paracetamol; topical NSAIDs for localised pain |
| Tricyclic antidepressants | Strong anticholinergic; orthostatic hypotension; cardiac arrhythmia | SSRIs (monitor bone density — see SSRI warning) |
| First-generation antipsychotics | Extrapyramidal effects, tardive dyskinesia, QTc prolongation | Lowest effective dose second-generation if essential |
| Meperidine / pethidine | Active metabolite normeperidine accumulates → seizures | Morphine or oxycodone at appropriate doses |
| Glibenclamide (glyburide) | High hypoglycaemia risk (long-acting; active metabolite) | Glipizide (shorter t½); SGLT2 or GLP-1 agent |
| Muscle relaxants (cyclobenzaprine) | Sedation, anticholinergic, falls risk | Physiotherapy; low-dose short-duration if necessary |
Deprescribing: how to reduce medication burden safely
Deprescribing is the planned, supervised process of dose reduction or cessation of medications that are no longer appropriate. It requires:
- Medication reconciliation — list ALL medications including OTC, supplements, and herbal products (e.g. St John's Wort affects CYP3A4)
- Indication review — for each drug, confirm the indication is current and still valid (e.g. a bisphosphonate started for osteoporosis 10 years ago may warrant a drug holiday)
- Risk-benefit reassessment — consider remaining life expectancy, goals of care, and whether benefit is realistic (statins in frailty with <2 year prognosis provide little benefit)
- Prioritise drugs with withdrawal risk — taper benzodiazepines (≥4 weeks), SSRIs/SNRIs (to avoid discontinuation syndrome), opioids, beta-blockers, corticosteroids
- Monitor after withdrawal — watch for rebound (hypertension rebound after stopping antihypertensives, angina after stopping nitrates)
Resources: Deprescribing.org protocols ↗, MedStopper clinical decision tool ↗, NICE NG5 multimorbidity guideline ↗.