Paracetamol

Question 1

What are indications for paracetamol?

Answer 1

Mild to moderate analgesia and fever

Question 2

Describe pharmacokinetics of paracetamol

Answer 2

Half life - 2 hrs

Predominantly inactivated by conjugation in the liver

Question 3

What is NAPQI?

Answer 3

Minor oxidation product of paracetamol - highly reactive

At normal, therapeutic doses it’s conjugated w/ glutathione and made harmless
However hepatic glutathione is limited

Question 4

Describe paracetamol overdose

Answer 4

Levels of NAPQI overwhelm levels of hepatic glutathione
NAPQI => oxidises thiol groups on key metabolic enzymes => cell death (necrosis and apoptosis) => hepatocellular and renal damage

150mg/kg is enough to cause irreversible damage: 10-20 tablets on one dose

Question 5

What are some Sx of paracetamol overdose?

Answer 5

Can be asymptomatic for many hours

First 24 hrs: nausea, vomiting, abdo pain
24-48 hrs: liver damage, upper quadrant pain
3-4 days: maximum liver damage

Prothrombin time is indicator of damage

Question 6

What is the antidote for paracetamol overdose?

Answer 6

Acetylcysteine - precursor for glutathione