Drug Safety, Pharmacovigilance, and Toxicology
Safety questions ask you to judge causality, act on a signal, and manage a poisoned patient, often under time pressure.
Core framework
- ADR types: A (dose-related, predictable, common), B (idiosyncratic, unpredictable, often serious), plus D (delayed), E (end of use) and F (failure of therapy).
- Seriousness criteria: death, life-threatening event, hospitalisation or prolongation, persistent disability, congenital anomaly, medically important event.
- Causality: WHO-UMC categories (certain, probable, possible, unlikely, unassessable) or the Naranjo score - temporal relationship, dechallenge, rechallenge, alternative causes.
- Poisoning: ABCDE first, then decontamination (activated charcoal within about one hour if the airway is protected), then antidote and enhanced elimination.
Antidotes to know
Paracetamol - N-acetylcysteine; opioid - naloxone; warfarin - vitamin K plus prothrombin complex; organophosphate - atropine and pralidoxime; methanol or ethylene glycol - fomepizole or ethanol; iron - deferoxamine; digoxin - digoxin-specific Fab; isoniazid - pyridoxine.
Worked example
A 60 kg adult ingests 10 g of paracetamol at once. Dose = 10,000 mg / 60 kg ≈ 167 mg/kg, above the ~150 mg/kg (or 7.5 g) referral threshold. Measure the plasma level at 4 hours and plot it on the treatment nomogram; if above the line, start N-acetylcysteine. Do not wait for symptoms - early treatment prevents hepatic failure.
Traps
Equating frequency with causality; not reporting a reaction because it is already in the label (report it anyway); forgetting mg/kg dosing in children; giving activated charcoal to a drowsy patient with an unprotected airway.