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.
The Bottom Line
- Type A (augmented): dose-dependent, predictable, common, usually mild. E.g. hypoglycaemia from insulin, bleeding from warfarin
- Type B (bizarre): dose-independent, idiosyncratic, unpredictable, rare but often severe. E.g. anaphylaxis to penicillin, SJS from carbamazepine
- ADRs account for ~6.5% of hospital admissions — 4th commonest cause of death in hospitalised patients
- Report all suspected ADRs via MHRA Yellow Card scheme — especially for new drugs (▼ black triangle)
- Key drug-ADR pairings: methotrexate → myelosuppression/pneumonitis; amiodarone → thyroid/pulmonary/liver/skin; ACEi → cough/angioedema; statins → myopathy/rhabdomyolysis
Overview
An adverse drug reaction is any unwanted or harmful reaction from a medicine at normal therapeutic doses. The Rawlins-Thompson classification divides ADRs into type A (augmented — predictable, dose-dependent extensions of pharmacological action) and type B (bizarre — unpredictable, not dose-related, often immunological or genetic). Additional types include C (chronic), D (delayed, e.g. carcinogenesis), and E (end-of-use/withdrawal). ADRs are a major cause of morbidity, mortality, and healthcare cost.
Epidemiology
ADRs account for approximately 6.5% of UK hospital admissions with annual NHS cost exceeding £1 billion. The most commonly implicated drugs include NSAIDs, anticoagulants, diuretics, ACE inhibitors, and antibiotics. Polypharmacy (≥5 medications) dramatically increases risk — particularly in the elderly where pharmacokinetic changes compound the problem. Women, elderly patients, and those with renal/hepatic impairment are at highest risk.
Clinical Features
Symptoms
GI: nausea, vomiting, diarrhoea (antibiotics, NSAIDs, metformin), constipation (opioids, CCBs)
Skin: rash, urticaria (antibiotics, allopurinol), photosensitivity (doxycycline, amiodarone)
CNS: drowsiness (antihistamines, opioids), dizziness (antihypertensives), confusion (anticholinergics)
Hepatic: jaundice, RUQ pain (statins, methotrexate, anti-TB drugs, paracetamol overdose)
Renal: AKI (NSAIDs, ACEi, gentamicin, contrast media)
Haematological: myelosuppression (methotrexate, carbimazole, clozapine), bleeding (warfarin, DOACs)
Anaphylaxis: urticaria, angioedema, bronchospasm, cardiovascular collapse (penicillins, NSAIDs)
SJS/TEN: widespread skin/mucosal blistering (carbamazepine, allopurinol, sulfonamides, lamotrigine)
Signs
Temporal relationship between drug initiation/dose change and symptom onset
Improvement on drug withdrawal (dechallenge)
Signs specific to the ADR: rash, jaundice, bleeding, petechiae, altered consciousness
Investigations
First-line
Drug history reviewComplete medication reconciliation including OTC, herbal, recreational. Establish temporal relationship
Bloods guided by suspected ADRFBC (myelosuppression), U&Es (AKI), LFTs (hepatotoxicity), CK (rhabdomyolysis), INR (warfarin), drug levels (lithium, digoxin, gentamicin, phenytoin)
Second-line
Specific drug levelsNarrow therapeutic index drugs: lithium (0.4–1.0), digoxin (<2 ng/mL), phenytoin (10–20 mg/L), gentamicin (trough <1), theophylline
TryptaseIf anaphylaxis suspected — take within 1–6 hours
Specialist
HLA typingPre-prescription: HLA-B*5701 before abacavir, TPMT before azathioprine, HLA-B*5801 before allopurinol in specific populations
1
Stop the offending drug
- Remove suspected drug if clinically safe
- If essential with no alternative: dose reduction, switch formulation, add gastroprotection
- Some ADRs require switch not cessation (ACEi cough → switch to ARB)
2
Treat the ADR
- Anaphylaxis: IM adrenaline 1:1000 (500 mcg), ABCDE, IV fluids, chlorphenamine, hydrocortisone
- SJS/TEN: stop ALL potential causative drugs, ITU/burns unit (mortality up to 30% for TEN)
- Drug-induced AKI: stop nephrotoxin, IV fluids
- Opioid toxicity: naloxone 400 mcg IV (repeat every 2–3 min)
3
Report via Yellow Card
- Report ALL suspected ADRs for new drugs (▼ black triangle)
- Report SERIOUS or UNEXPECTED ADRs for established drugs
- Patients, pharmacists, nurses, and doctors can all report
- Online: yellowcard.mhra.gov.uk
4
Prevention
- Prescribe per BNF, check allergies, interactions, renal/hepatic function
- Avoid polypharmacy — regular medication reviews in elderly
- Check TPMT, HLA typing, and drug levels where indicated
- "Start low, go slow" in elderly
Complications
- Death: 4th leading cause of hospital death — anticoagulant bleeding, anaphylaxis, SJS/TEN
- Prolonged hospitalisation: ADRs increase stay by 1–4 days
- Permanent organ damage: Renal failure (gentamicin), hearing loss (aminoglycosides), peripheral neuropathy (isoniazid)
- Loss of therapeutic options: True allergy restricts future prescribing
UKMLA Exam Tips
- 1Type A = Augmented (dose-related, predictable, common). Type B = Bizarre (idiosyncratic, unpredictable, rare but serious)
- 2HIGH-YIELD drug-ADR pairs: amiodarone (thyroid, lung fibrosis, liver, corneal deposits, photosensitivity); methotrexate (myelosuppression, pneumonitis, hepatotoxicity); ACEi (dry cough ~15%, angioedema); statins (myopathy → rhabdomyolysis)
- 3Narrow therapeutic index drugs: lithium, digoxin, phenytoin, gentamicin, theophylline, warfarin
- 4SJS/TEN culprits: carbamazepine, allopurinol, lamotrigine, sulfonamides. <10% BSA = SJS, >30% = TEN
- 5TPMT before azathioprine. HLA-B*5701 before abacavir. These are pre-prescription safety checks
- 6Yellow Card: report ALL ADRs for ▼ drugs. Report serious/unexpected ADRs for all drugs
- 7Serotonin syndrome: SSRIs + MAOIs or tramadol → agitation, clonus, hyperthermia. QT prolongation: amiodarone, macrolides, antipsychotics, methadone
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