Describe the pharmacological effects of paracetamol. Outline its toxicity and management.
Main points expected for a pass included:
· Actions and mechanism of actions of paracetamol. These include inhibition of cyclooxygenase (COX) activity and prevention of prostaglandin (PG) production. More marks were given for mention of a central COX 1 variant as the possible enzyme responsible for paracetamol’s central versus peripheral effects. Knowledge of the central sites of action was expected.
· Outline of toxicity. Candidates were expected to demonstrate knowledge of toxic doses, conditions enhancing toxicity (alcohol intake, chronic use etc), and the mechanism of hepatic toxicity and other organ toxicity (especially renal). A detailed list of clinical features of toxicity was not required.
· Management of toxicity. Candidates performed well in this section with good knowledge of timing, toxic doses, use of paracetamol levels and the nomogram to determine whether N-acetylcysteine should be administered. Mechanism of action of NAC was expected. Mention of monitoring (liver failure) and supportive therapy gained marks, but detailed explanations were not required
Stoelting 4th edition page 285
Rand Dale 5th page 244
We forgive the examiners for their unfair expectations here, as this was one of the first CICM primary exam papers, and they were still trying to determine exactly how unfair they could expect to be. Certainly "describe the pharmacological effects" sounds like a pharmacodynamics question, but paracetamol is one of those drugs that defies classification, and there are about ten different explanations for its analgesic and antipyretic effects.
Graham, Garry G., et al. "The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings." Inflammopharmacology 21.3 (2013): 201-232.
Jefferies, Sarah, Manoj Saxena, and Paul Young. "Paracetamol in critical illness: a review." Critical Care and Resuscitation 14.1 (2012): 74-80.
Prescott, L. F. "Kinetics and metabolism of paracetamol and phenacetin." British journal of clinical pharmacology 10.S2 (1980): 291S-298S.