Paracetamol Overdose
A toxic metabolite overwhelms the liver's glutathione defences once conjugation pathways saturate, causing centrilobular hepatocyte necrosis that the antidote works by replenishing.
In a nutshell
Overdose saturates paracetamol's normal conjugation pathways, shunting more drug through CYP2E1 to the toxic metabolite NAPQI, which depletes glutathione and causes centrilobular hepatocyte necrosis. NAC works by replenishing glutathione before that damage becomes irreversible.
Classic presentation
A patient who looks well or has only mild nausea in the first day after ingestion, then develops right upper quadrant pain and deranged liver function over the following days.
Key points
- The early silent window is the danger: normal observations in the first 24 hours do not exclude a serious ingestion.
- The treatment nomogram only applies to a single acute ingestion with a reliably known timing; staggered or uncertain ingestions are treated empirically.
- NAC is a glutathione precursor: it works by restoring the very defence that overdose depletes.
- King's College criteria (acidosis, INR, creatinine, encephalopathy) identify patients needing liver transplant referral.
First-line investigation
A paracetamol level taken at or after 4 hours post-ingestion, plotted on the treatment nomogram.
First-line management
N-acetylcysteine, guided by the nomogram for a known single ingestion or given empirically for staggered or uncertain-time overdoses.
Exam traps
- A level taken before 4 hours cannot be interpreted on the nomogram. It must be repeated.
- Feeling well in the first 24 hours does not exclude severe toxicity; hepatic injury lags behind ingestion.
- Staggered overdose bypasses the nomogram entirely: treatment decisions are made on history and risk, not a single level.
Educational content pending clinical review. Not medical advice.