Adverse Drug Effects

Adverse drug effects are unintended, harmful reactions to medications that occur at normal therapeutic doses. They are a major cause of morbidity and mortality, contributing to ~6–7% of hospital admissions in the UK. A systematic approach is crucial for recognising, classifying, and preventing ADEs.

📖 Introduction

• Defined by WHO as: "a response to a drug which is noxious, unintended, and occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy."
• Affect up to 1 in 10 inpatients, with elderly and polypharmacy patients at greatest risk.
• Different from medication errors (wrong drug/dose) but may overlap.

🧬 Pathophysiology

• Pharmacological effects (dose-related toxicity, predictable).
• Immune-mediated hypersensitivity (allergic reactions, unpredictable).
• Idiosyncratic reactions (unusual, genetic or metabolic basis).
• Drug–drug and drug–disease interactions (e.g. NSAIDs + CKD → AKI).

⚖️ Classification (Rawlins & Thompson)

🩺 Clinical Assessment

• 📝 History: Timeline of drug exposure, dose, indication, and onset of symptoms.
• 📋 Drug list: Include prescriptions, OTC, herbal supplements.
• 🔎 Exam: Rash, jaundice, bleeding, confusion, renal/hepatic signs.
• 🧪 Investigations: FBC (agranulocytosis), U&E (renal toxicity), LFTs (hepatotoxicity), INR (warfarin control).
• 📈 Causality tools: Naranjo algorithm (probable vs possible ADR).

⚠️ Risk Factors

• 👴 Elderly age.
• 💊 Polypharmacy (>5 drugs).
• 🧬 Genetic factors (slow acetylators, HLA types).
• 🩺 Comorbidities: renal, liver, cardiac disease.
• 🚺 Pregnancy, paediatrics (altered pharmacokinetics).

📊 Comprehensive Summary Table - Adverse Drug Effects

💉 Management

• ⛔ Stop the suspected drug if safe to do so.
• 🔄 Switch to alternative if therapy essential.
• 🛡️ Supportive treatment: fluids, oxygen, antihistamines, steroids, adrenaline in anaphylaxis.
• 📊 Monitor organ function (renal, hepatic, haematological).
• 📢 Report ADRs via MHRA Yellow Card Scheme (UK requirement).
• 👨‍👩‍👧 Patient education: carry allergy cards, warn about recurrence risk.

📌 Prevention

• 💊 Prescribe lowest effective dose.
• 🔎 Regular medication review (esp. elderly, polypharmacy).
• 🧬 Pharmacogenomic testing where appropriate (e.g. HLA-B*57:01 before abacavir).
• 📚 Use BNF & NICE guidelines for safe prescribing.
• 🤝 Multidisciplinary working with pharmacists.

📚 Key References

• BNF – British National Formulary (latest edition).
• NICE Guidance: Medicines optimisation (NG5).
• MHRA Yellow Card Scheme: Report an ADR.

💡 Summary: Adverse drug effects are common and preventable. Always think: Is this symptom due to a drug? Early recognition, withdrawal of culprit, supportive treatment, and reporting are the pillars of safe practice.

Cases - Adverse Drug Effects (ADEs)

• Case 1 (ACE inhibitor → angioedema): 💊😮 A 63-year-old man started on ramipril for hypertension presents 3 weeks later with facial swelling, lip oedema, and difficulty speaking. No rash or pruritus.
  Management: Ramipril stopped immediately. Treated with IV steroids and antihistamines; monitored in hospital.
  Outcome: Swelling subsided within 24 hours. Switched to amlodipine for blood pressure control. Counselled to avoid ACE inhibitors in future.
• Case 2 (NSAID → AKI + GI bleed): 💊🩸 A 70-year-old woman with osteoarthritis has been taking ibuprofen daily for several months. She presents with melaena, dizziness, and reduced urine output. Bloods: Hb 85 g/L, creatinine 250 µmol/L.
  Management: IV fluids, PPI infusion, blood transfusion, and urgent OGD which identifies and clips a bleeding gastric ulcer. NSAIDs discontinued.
  Outcome: Renal function gradually recovered. Pain managed with paracetamol and topical agents instead.
• Case 3 (Amiodarone → thyroid dysfunction): 💊🦋 A 58-year-old man on amiodarone for atrial fibrillation presents with weight loss, tremor, and palpitations. TFTs show suppressed TSH and elevated free T4 = amiodarone-induced thyrotoxicosis.
  Management: Amiodarone stopped after cardiology review. Treated with carbimazole and steroids. Endocrinology follow-up arranged.
  Outcome: Thyroid function normalised after 6 months. Patient later switched to alternative rhythm-control therapy.

🧑‍⚕️ Teaching Commentary

Adverse drug effects can occur via several mechanisms: • Idiosyncratic (ACE inhibitor angioedema). • Predictable dose-related (NSAID-induced AKI and GI bleed). • Metabolic/endocrine (amiodarone-induced thyroid disease). 🔑 Always review drug history in any acute presentation, and consider: stop the offending drug, treat the complication, and find a safer alternative. Documenting ADEs clearly prevents recurrence and improves patient safety.