Paracetamol an analgesic and antipyretic which is typically classed as an NSAID, though it is unique and important enough to get its own page. It has a number of mechanisms of action:

  • Non-selective COX inhibition, including COX-3
    This confers some of the analgesic properties
  • Inhibition of central prostaglandin synthesis
    This confers the antipyretic effect by inhibiting prostaglandin E synthesis in the anterior hypothalamus in response to pyrogens
  • Serotonergic inhibition
    Provides some additional analgesic action
  • Cannabinoid inhibition
    Provides some additional analgesic action via endocannabinoid reuptake inhibition.

Property Effect
Class NSAID, acetanilide derivative
Uses Analgesia, antipyretic
Presentation Tablets, capsules, syrup, clear colourless solution for IV administration
Route of Administration PO/PR/IV
Dosing Q4H up to
Onset IV: 5 mins, peak at 40 mins
PO/PR: 40 mins, peak at 1 hour
Absorption Rapid absorption (via small bowel, therefore proportional to gastric emptying), variable bioavailability (up to 90%) - greater by PR route
Distribution 10% protein bound, small VD: (though larger than other NSAIDs)
Metabolism Predominantly hepatic glucuronidation. However, 10% is metabolised to NAPQI by CYP2E1 which is hepatotoxic.
Elimination Active secretion into renal tubules - consider dose reduction in renal impairment
Resp May exacerbate analgesic asthma due to glutathione depletion
CNS Excellent analgesia. Synergistic with other analgesics, resulting in agent-sparing effect and reduced side effects
Metabolic Antipyretic
Haeme Cytopaenias (rare)


  • Paracetamol is partially metabolised to the toxic N-acetyl-p-amino-benzoquinone imine (NAPQI)
    • In normal circumstances this rapidly conjugated with glutathione
    • In toxicity, glutathione is exhausted
    • NAPQI then covalently binds to critical proteins in hepatocytes, causing centrilobular hepatic necrosis and cell death
  • Toxic doses:
    • > in a single ingestion
    • Repeated ingestion of > for two days
    • > for three days
  • Risk factors for toxicity:
    • Glutathione deficiency
      • Extremes of age
      • Malnutrition
      • Hepatic dysfunction
    • Enzyme inducers:
      • Anti-epileptics
        • Carbamazepine
        • Phenytoin
        • Phenobarbitone
      • Rifampicin
      • ETOH
      • OCP

Features of Overdose

  • Conscious
  • Nausea, vomiting, and epigastric pain
  • Haemolytic anaemia
  • Distributive shock
  • Hyperglycaemia
  • Late (>48 hours) hepatic failure
  • Later (3-5 days) coagulopathy
  • Fulminant hepatic failure (3-7 days)

Treatment of Overdose

  • Activated charcoal with tablet ingestion if seen within 1 hour of ingestion.
  • Serum paracetamol level to determine requirement for NAC (N-acetylcysteine) based on the nomogram
    • IV NAC is used as it is a glutathione precursor, replenishing depleted glutathione and facilitating further conjugation of NAPQI


  1. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  2. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  3. Paracetamol Poisoning. Royal Children's Hospital.
  4. Hinson JA, Roberts DW, James LP. Mechanisms of Acetaminophen-Induced Liver Necrosis. Handbook of experimental pharmacology. 2010;(196):369-405.
Last updated 2019-07-18

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