Paracetamol

Question 1

What drug type is paracetamol?

Answer 1

Non NSAID and non-optiate

Question 2

What action does paracetamol produce?

Answer 2

Mild to moderate analgesia and antipyretic

Question 3

What is the hypothesis mechanism of action?

Answer 3

COX-2 selective inhibition in CNS and peroxidases in peripheral inflammation

Question 4

How is paracetamol metabolised?

Answer 4

At Norma therapeutic dose, it is conjugated with glutathione - but this is limited.

Question 5

Why is paracetamol so toxic at high doses?

Answer 5

Hepatic glutathione is limited and therefore the excess paracetamol is metabolised as NAPQI. NAPQI is highly nucleophilic, oxidising key metabolic enzymes and leading to necrosis and apoptosis. 150mg/kg is sufficient to cause irreversible damage.

Question 6

What are the signs of paracetamol overdose?

Answer 6

Can be asymptomatic for hours.
Within 24hrs get nausea, vomiting and abdominal pain.
Maximal liver damage occurs within 3-4 days.

Bloods taken >4hrs show the extent of overdose.

Question 7

What is the treatment for paracetamol overdose?

Answer 7

Glutathione thiol replacement- IV acetylcysteine
Unable to give direct glutathione - doesn’t get absorbed into the hepatocytes.
Drives the phase 2 metabolism.