Question 12 from the second paper of 2021 and Question 9 from the first paper of 2014 were the only past paper SAQs to ask about paracetamol toxicity directly. This topic's representation in the exam in disproportionate to its prevalence in practice. It certainly comes up more often if one works in a "liver unit", but its appearance in ICUs elsewhere is sufficiently common that it should warrant more of a discussion.
Question 9 from the first paper of 2014 asked "how paracetamol causes liver dysfunction". The most satisfying answer is probably found in the 2003 article by James et al, "Acetaminophen-induced hepatotoxicity." It was used as the source for the diagram below.
In wordy form, as befitting a college SAQ answer:
This is where N-acetylcysteine comes in.
Thankfully, in truly massive overdose, very little paracetamol is absorbed initially, so by the time the rest of the drug ends up in the circulation there should be enough NAC around to prevent acute liver failure.
There is a recommended dosage schedule for N-acetylcysteine:
Apparently, even if it is administered very late after an overdose, NAC may still have some benefit. Proper liver failure does not become established until after 48-72 hours.
In situations where one is unsure whether or not to treat the overdose, and the overdose has occurred less than 24 hours ago, one may use the Prescott nomogram which can help identify the patients who need to be treated.
But, when in doubt, Oh's manual recommends to treat anyway.
Its very hard to kill a person with N-acetylcysteine.
Question 12 from the second paper of 2021 required some discussion of the management of paracetamol toxicity, in particular where a sustained release formulation is taken. The answer was mainly based on the 2020 Australian guidelines, summarised in this article by Chiew et al for the MJA.
Chiew, Angela L., et al. "Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand." Medical journal of Australia 212.4 (2020): 175-183.
Daly, Frank FS, et al. "Guidelines for the management of paracetamol poisoning in Australia and New Zealand-explanation and elaboration." Medical journal of Australia 188.5 (2008): 296.
James, Laura P., Philip R. Mayeux, and Jack A. Hinson. "Acetaminophen-induced hepatotoxicity." Drug metabolism and disposition 31.12 (2003): 1499-1506.
Bailey, Benoit, René Blais, and Anne Letarte. "Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death." Annals of emergency medicine 44.4 (2004): 401-406.
Ding, G. K. A., and N. A. Buckley. "Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity." QJM101.9 (2008): 723-729.