Paracetamol Metabolism

Question 1

What is a toxic dose of paracetamol? When should Rx for overdoes be administered?

Answer 1

10 g

N-acetylcysteine within 2 hrs excellent prognosis. Within 8 hrs good. After death from liver failure may be inevitable.

Question 2

Where is it metabolised?

Answer 2

Liver

Question 3

Describe paracetamol metabolism and toxicity.

Answer 3

Undergoes Phase 2 conjugation with glucoronide and sulphate to produce non-toxic metabolites. However, in toxic doses (10g) this pathway is saturated and it enters Phase 1 metabolism, producing toxic NAPQI. NAPQI is a strong oxidising agent, causing covalent binding of hepatic proteins. It undergoes Phase 2 conjugation with glutathione, depleting this antioxidant. This causes hepatocytes destruction, liver failure within days and death if no Rx.

Question 4

What is Rx for paracetamol overdose?

Answer 4

N-acetylcysteine

Question 5

How does N-acetylcysteine treat paracetamol overdose.

Answer 5

It replenishes glutathione stores, allowing liver hepatocytes to metabolise NAPQI safely.

Question 6

Signs of paracetamol overdose?

Answer 6

1. Transaminases in blood (elevated ALT) - liver necrosis
2. Encephalopathy
3. Jaundice
4. Hypoglycaemia - decreased gluconeogenesis

Question 7

Syx?

Answer 7

Most pts are asymptomatic for first 24 hrs or

1. N
2. V
3. RUQ pain

Question 8

When can serum paracetamol levels be detected?

Answer 8

4 hrs post ingestion

Question 9

What is the usual dose of paracetamol?

Answer 9

1 or 2 500mg tables at a time, not more than 4g/day