Paracetamol Metabolism

Question 1

What is the normal products of paracetamol?

Answer 1

Glucuronide and sulphate - non toxic

Question 2

When high levels of paracetamol are consumed what is the product of its metabolism? Why is this bad?

Answer 2

NAPQI

Because it is very toxic

Question 3

What are the direct toxic effects that NAPQI has?

Answer 3

Lipid peroxidation
Damage to proteins
Damage to DNA

All within the liver

Question 4

How does the body attempt to stop NAPQI from causing oxidative damage? Why can this be a bad idea?

Answer 4

By reacting it with glutathione (GSH).

Bad because;

• The stores of glutathione will eventually run out
• glutathione depletion will also result in oxidative damage because it normal defends against it

*the damage caused is irreversible so treatment for paracetamol overdoses must be given straight away!!

Question 5

How is a paracetamol overdose treated? How does this work?

Answer 5

Give N-acetylcysteine

It works by replenishing the glutathione levels.
Essentially you allow the body to remove the NAPQI itself but you must save the persons liver by boosting the glutathione levels.