Pharmacology Notes

Acetylcysteine is the antidote for paracetamol overdose. N-acetyl-p-benzoquinoneimine (NABQI) [Note 1] is the potentially hepatotoxic intermediate produced during paracetamol metabolism. This intermediate is usually conjugated by glutathione to non-toxic metabolites, which are excreted. In the setting of paracetamol overdose, glutathione stores are consumed resulting in a build-up of NABQI. Acetylcysteine is a glutathione precursor and replenishes glutathione stores, allowing the intermediate toxic metabolite to be conjugated to non-toxic metabolites. Acetylcysteine is thought to have other mechanisms of action including antioxidant properties that may be useful in treating fulminant liver failure due to a variety of causes, and in improving liver haemodynamics.

For paracetamol overdose in Australia, acetylcysteine is administered as a series of three infusions over approximately 20 hours. The initial bolus is given over 15 to 60 minutes. Some patients may benefit from an extended duration of therapy of up to 48 hours or even longer if there is evidence of liver injury. Such patients should be discussed with a toxicologist or specialist liver unit.

Acetylcysteine is most effective if initiated within eight hours of paracetamol ingestion, but there is no time that is 'too late' to give acetylcysteine.

Numerous cases of incorrect dose calculations have occurred with the administration of acetylcysteine, often resulting in under-dosing. The dose and volume of acetylcysteine to be added to each infusion should be carefully checked. See Antidotal therapy: acetylcysteine.

Acetylcysteine is generally well tolerated. Non-IgE mediated allergic reactions and anaphylaxis are not uncommon but are usually only mild to moderate with rash, urticaria and flushing. Bronchospasm and hypotension are rare. If such reactions occur, cease the infusion and recommence at a slower rate. Such reactions may be more common in asthmatics. Reactions not responding to slowing the infusion rate may need to be managed as for anaphylaxis. The rate of infusion of the loading dose does not appear to affect the risk of adverse reactions.