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ukmla 2026

Pharmacokinetics in Special Populations

Drug handling is significantly altered in renal impairment, hepatic impairment, pregnancy, neonates, and the elderly — requiring dose adjustment, drug avoidance, or enhanced monitoring

Review date
reviewed 2026-04-05
Reading time
5 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Clinical Pharmacologycommonchronic
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Condition details
Clinical Pharmacology
common
5 min read
reviewed 2026-04-05
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About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

Key points

  • Renal impairment: reduce dose or frequency of renally excreted drugs (gentamicin, metformin, DOACs, lithium, digoxin). Check eGFR before prescribing
  • Hepatic impairment: avoid hepatotoxic drugs, reduce doses of hepatically metabolised drugs (opioids, benzodiazepines, warfarin). Use Child-Pugh score
  • Pregnancy: avoid teratogens (methotrexate, warfarin, ACEi, retinoids, valproate, lithium). Use BNF Appendix 4 and UK Teratology Information Service
  • Elderly: "start low, go slow". Increased sensitivity to sedatives, anticholinergics, and cardiovascular drugs. Polypharmacy review essential
  • Neonates: immature hepatic metabolism (CYP450) and renal excretion. Increased Vd for water-soluble drugs. Grey baby syndrome with chloramphenicol

Overview

Pharmacokinetics (absorption, distribution, metabolism, excretion) varies significantly across special populations. In renal impairment, reduced GFR leads to accumulation of renally cleared drugs. In hepatic impairment, reduced first-pass metabolism increases bioavailability, and impaired drug metabolism prolongs half-life. In pregnancy, physiological changes (increased plasma volume, increased GFR, altered protein binding) alter drug levels, and teratogenic risk is paramount. In the elderly, reduced renal function, hepatic mass, lean body mass, and total body water alter pharmacokinetics, while increased receptor sensitivity alters pharmacodynamics. In neonates, immature enzyme systems and organ function require specialised dosing.

Epidemiology

Approximately 40% of hospitalised patients have some degree of renal impairment. Polypharmacy (≥5 medications) affects over 50% of patients aged >65 and is a major driver of ADRs in the elderly. Drug-related problems are estimated to cause 5–8% of hospital admissions in the elderly. Prescribing in pregnancy requires particular caution — approximately 50% of pregnancies involve some drug exposure, and valproate alone causes an estimated 450 major birth defects per year in the UK when used in pregnancy.

Clinical Features

Symptoms
This topic covers pharmacological principles rather than a specific clinical presentation
Signs

Investigations

First-line
eGFR/creatinine clearanceEssential before prescribing any renally cleared drug. Use Cockcroft-Gault for drug dosing (not CKD-EPI)
LFTs and Child-Pugh scoreAssess hepatic function — guides dose reduction for hepatically metabolised drugs
Second-line
Drug levelsMonitor narrow TI drugs more frequently in special populations
Pregnancy testBefore prescribing any potentially teratogenic drug to women of childbearing age

Management

BNF Appendices (Renal, Hepatic, Pregnancy, Breastfeeding, Elderly)
1
Renal impairment
  • Check eGFR before prescribing and adjust doses per BNF Appendix 3
  • Avoid or dose-reduce: metformin (eGFR <30 = stop), gentamicin, lithium, digoxin, DOACs, opioids (use reduced doses of morphine or switch to fentanyl/buprenorphine)
  • NSAIDs: avoid in CKD — reduce renal blood flow and worsen kidney function
  • ACEi/ARBs: beneficial in CKD with proteinuria but monitor K+ and creatinine (accept up to 30% rise in creatinine)
2
Hepatic impairment
  • Reduce doses of hepatically metabolised drugs: opioids (use lower doses, avoid codeine), benzodiazepines (use shorter-acting, e.g. lorazepam), warfarin
  • Avoid hepatotoxic drugs: methotrexate, paracetamol (lower toxic threshold), statins (if ALT >3x ULN)
  • Increased sensitivity to sedatives — can precipitate hepatic encephalopathy
  • Use Child-Pugh score to guide dose adjustments
3
Pregnancy
  • KEY TERATOGENS to avoid: Valproate (neural tube defects, developmental delay), Warfarin (nasal hypoplasia, stippled epiphyses, CNS abnormalities — use LMWH instead), ACE inhibitors/ARBs (renal agenesis), Retinoids (craniofacial and cardiac defects), Methotrexate (folate antagonist — limb and CNS defects), Lithium (Ebstein anomaly), Carbamazepine and phenytoin (neural tube defects, cleft palate)
  • Safe(r) alternatives: paracetamol (analgesic), penicillins/cephalosporins (antibiotics), labetalol/nifedipine (hypertension), insulin (diabetes), lamotrigine (epilepsy — lowest teratogenic risk AED)
  • Always check BNF Appendix 4 and UKTIS (UK Teratology Information Service) before prescribing
  • Pregnancy Prevention Programme for valproate — must NOT be prescribed to women of childbearing potential unless on the programme
4
Elderly
  • "Start low, go slow" — begin with the lowest dose and titrate gradually
  • Avoid anticholinergics (confusion, falls, urinary retention), long-acting benzodiazepines (falls), tricyclics
  • Regular medication review — STOPP/START criteria, deprescribing when appropriate
  • BEERS criteria and STOPP/START criteria guide appropriate prescribing in older adults
  • Increased sensitivity to warfarin, opioids, antihypertensives (postural hypotension risk)

Complications

  • Teratogenicity: Fetal abnormalities from drug exposure in pregnancy
  • Drug accumulation: In renal/hepatic impairment leading to toxicity
  • Falls in the elderly: From sedatives, antihypertensives, anticholinergics
  • Polypharmacy cascade: Prescribing new drugs to treat side effects of existing drugs
UKMLA Exam Tips
  • 1Teratogens mnemonic: "WRATH" — Warfarin, Retinoids, ACEi, Thalidomide/Tetracyclines, (H) Valproate/Methotrexate
  • 2Valproate in pregnancy: Pregnancy Prevention Programme is MANDATORY — must have effective contraception and annual review
  • 3Metformin: stop if eGFR <30. Reduce dose if eGFR 30–45
  • 4Warfarin is teratogenic — use LMWH in pregnancy (does not cross the placenta)
  • 5Codeine should be avoided in renal impairment — its active metabolite (morphine) accumulates. Use buprenorphine or fentanyl instead
  • 6Grey baby syndrome = chloramphenicol in neonates — immature glucuronidation
  • 7"Start low, go slow" in the elderly — and review regularly for deprescribing opportunities

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Verified Sources & References

BNF — Prescribing in renal/hepatic impairment
UK Teratology Information Service (UKTIS)
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