PARACETAMOL POISONING

Paracetamol (Acetaminophen) poisoning is one of the most common causes of liver toxicity worldwide. It typically results from taking more than the recommended dose, either accidentally or intentionally, leading to potentially fatal liver damage if not treated promptly.

1. Mechanism of Toxicity

  • Normal Metabolism: At therapeutic doses, most paracetamol is metabolized in the liver by conjugation with sulfate and glucuronide to form non-toxic compounds. A small percentage is converted by the cytochrome P450 enzyme system into a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI).

  • Toxic Doses: When the dose exceeds the liver’s normal processing capacity, more paracetamol is converted to NAPQI, which depletes glutathione (a natural antioxidant that detoxifies NAPQI). Once glutathione is exhausted, NAPQI binds to liver cell proteins, leading to cell death and potentially severe liver damage.

2. Toxic Doses

  • Adults: Toxicity typically occurs with doses >150 mg/kg or more than 7.5 grams in a single dose.

  • Children: Toxicity generally starts with doses >200 mg/kg.

3. Stages of Paracetamol Poisoning

  • Stage 1 (0–24 hours): Often no symptoms initially or mild symptoms such as nausea, vomiting, lethargy, and sweating. These can be easily overlooked or mistaken for other conditions.

  • Stage 2 (24–72 hours): Symptoms may improve briefly, but liver damage begins, with upper right abdominal pain, elevated liver enzymes (AST, ALT), and possible jaundice.

  • Stage 3 (72–96 hours): This is the most critical phase, with severe liver damage leading to hepatic failure. Symptoms include jaundice, hypoglycemia, coagulopathy, encephalopathy, and multi-organ failure. Death can occur without treatment.

  • Stage 4 (4 days to 2 weeks): Recovery phase, provided the patient survives Stage 3. Liver regeneration occurs, and liver function gradually returns to normal over weeks.

4. Diagnosis

  • Blood Tests: Plasma paracetamol levels should be measured, typically 4 hours after ingestion, using the Rumack-Matthew nomogram to assess risk and guide treatment.

  • Liver Function Tests: Elevated AST, ALT, bilirubin, and INR (for liver injury and liver function) are key indicators.

  • Renal Function Tests: Blood urea nitrogen (BUN) and creatinine are measured as kidney involvement may also occur.

5. Treatment

  • Activated Charcoal: Given within 1–2 hours of ingestion to reduce drug absorption from the stomach. Not effective if taken later.

  • N-Acetylcysteine (NAC): NAC is the antidote of choice, working by replenishing glutathione and directly neutralizing NAPQI. NAC is effective if administered within 8–10 hours after ingestion but can still benefit patients even at later stages.

  • Supportive Care: This includes managing complications like hypoglycemia, acidosis, and coagulopathy. Severe cases may require liver transplantation if liver failure progresses.

6. Prevention and Education

  • Clear Dosing Instructions: Educating patients on the maximum safe dose, particularly in children and people with liver disease.

  • Care with Multi-ingredient Products: Many over-the-counter medications contain paracetamol combined with other drugs, increasing the risk of unintentional overdose.

  • Prescription Limits: Limiting the quantity of paracetamol available in single purchases and raising awareness can reduce unintentional poisoning risks.