Paracetamol

Question 1

What is paracetamol and when is it used

Answer 1

A non-NSAID, non-opiate analgesic with anti-pyretic effects

Used for mild to moderate analgesia and fever

Question 2

Describe the pharmacokinetics of paracetamol

Answer 2

Paracetamol is well absorbed by the GI tract

Has a t1/2 of 2hrs

Is inactivated by conjugation in the liver

Question 3

What is the oxidation product of paracetamol and what is it produced by

Answer 3

NAPQI is minor oxidation product of paracetamol

Is produced by metabolism of paracetamol

NAPQI is then conjugated with glutathione to reduce its levels

Question 4

Why does a patient develop a paracetamol overdose if too much is taken - what is the mechanisms behind it

Answer 4

Hepatic glutathione is limited so balance of conjugation of paracetamol determies build up of NAPQI

NAPQI is highly nucleophilic and if levels rise it can cause apoptosis and necrosis

Question 5

What are the symptoms of a paracetamol overdose

Answer 5

Often asymptomatic for many hours

Have nausea, vomiting, abdominal pain after first 24hrs

Upper quadrant pain after 24-72hrs when there is liver damage

Question 6

What is given to treat paracetamol overdose

Answer 6

Acetylcysteine given intravenously

Given as a glutathione thiol replacement - acetylcysteine can enter hepatocytes while glutathione cannot