Drug-Induced Liver Injury (DILI)
• Common culprits: methotrexate, isoniazid, valproate, statins, nitrofurantoin, amiodarone
• Monitoring: LFTs routinely if on hepatotoxic agents (esp. methotrexate, statins)
• Patterns:
o Hepatocellular: ↑ ALT/AST (e.g. isoniazid, paracetamol)
o Cholestatic: ↑ ALP/GGT (e.g. co-amoxiclav)
o Mixed: e.g. phenytoin, sulfonamides
• Specifics:
o Methotrexate: fibrosis risk ↑ with alcohol; folic acid reduces risk
o Isoniazid: idiosyncratic hepatitis; check LFTs monthly
o Valproate: fatal hepatic failure (esp. in children); monitor during 6 months
o Statins: asymptomatic transaminitis; stop if ALT >3× ULN
o Paracetamol (overdose): centrilobular necrosis
Pancreatitis (Drug-Induced)
• Common causes: azathioprine, valproate, furosemide, didanosine, steroids
• Presentation: epigastric pain radiating to back, ↑ amylase/lipase
• Diagnosis: 2 of 3 — abdominal pain, ↑ enzymes, imaging
• Exclude: gallstones, alcohol
Syndrome of Inappropriate ADH Secretion (SIADH)
• Drugs causing SIADH:
o SSRIs
o Carbamazepine
o Vincristine
o Cyclophosphamide
• Features: euvolaemic hyponatraemia, confusion, seizures
• Management: fluid restriction, stop culprit drug ± demeclocycline/tolvaptan
Photosensitivity
• Drugs:
o Tetracyclines
o Amiodarone
o Sulfonamides
o Thiazides
• Presentation: exaggerated sunburn-like rash on sun-exposed areas
Gynaecomastia
• Causative drugs:
o Spironolactone (antiandrogenic)
o Digoxin (oestrogen-like structure)
o Cimetidine, Ketoconazole, Finasteride
• Mechanism: hormonal imbalance or oestrogenic effects
Hypothyroidism
• Drug causes:
o Amiodarone (high iodine load; also causes hyperthyroidism)
o Lithium (inhibits thyroid hormone release)
o Carbimazole/PTU: overtreatment
• Monitoring: TFTs every 6 months during therapy
Extrapyramidal Symptoms (EPS)
• Drugs: typical antipsychotics, metoclopramide
• EPS types:
o Acute dystonia: torticollis, oculogyric crisis
o Parkinsonism, akathisia, tardive dyskinesia
• Treatment:
o Acute dystonia: procyclidine, benztropine
o Stop causative drug
Bronchospasm
• Causative drugs:
o Non-selective beta-blockers (e.g. propranolol)
o NSAIDs (especially in aspirin-sensitive asthma)
• Avoid in patients with asthma or severe COPD
Myasthenia Gravis Exacerbation
• Drugs worsening weakness:
o Aminoglycosides
o Fluoroquinolones
o Magnesium
o Beta-blockers
• Presentation: ptosis, diplopia, limb weakness, dyspnoea
Pulmonary Fibrosis
• Offending agents:
o Amiodarone
o Methotrexate
o Nitrofurantoin
o Bleomycin
• Symptoms: dry cough, dyspnoea, crackles
• Investigations: CXR, HRCT, spirometry (restrictive defect)
Peripheral Neuropathy
• Causative drugs:
o Isoniazid (prevent with pyridoxine)
o Vincristine
o Amiodarone
o Cisplatin, Oxaliplatin
• Symptoms: glove-and-stocking numbness, paraesthesia
Serotonin Syndrome
• Triggers: SSRI + MAOI, SNRI, triptans, linezolid, MDMA
• Features:
o CNS: agitation, confusion
o Neuromuscular: clonus, hyperreflexia, tremor
o Autonomic: fever, sweating, tachycardia
• Management:
o Stop serotonergic agents
o Supportive care
o Cyproheptadine (serotonin antagonist) in moderate/severe cases
