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paracetamol (acetaminophen)


  • an antipyretic analgesic agent also known as acetaminophen in the USA
  • 1st synthesised in 1877
  • extensive use commenced around 1947, initially as prescription only in USA
  • OTC status gained in 1960 in USA
  • toxic effects 1st noted in 1971


  • rapidly absorbed from GIT - peak concentration 60-120mins if tablet or capsule form ingested
  • Vd 1.0-2.0L/kg
  • half life 1-3hrs but may increase to 17hrs in liver disease
  • metabolised by liver:
    • 52% by sulphation
    • 42% by glucuronidation
    • 2% excreted unchanged in urine
    • 4% biotransformed by C-P450 MFO system
    • but in overdose when glutathione stores are depleted, N-acetyl-p-benzoquinoneimine (NAPQI) accumulates and causes hepatocellular necrosis


  • antipyretic analgesic
  • inhibits brain prostaglandin synthetase
  • inhibits pain impulses peripherally
  • may also:
    • decrease empathy 1)
    • decrease feelings of joy
    • decrease anxiety and existential dread
    • have potential fetal effects when taken in pregnancy - unproven - further research needed


  • adults:
    • 500-1000mg 4-6hr prn (max. 4g per day - ie. 2 x 500mg tablets qid)
  • paed:
    • 15mg/kg/dose 4-6hr max. 90mg/kg/24hr 
    • a single evening stat dose up to 30mg/kg can be used with care as long as total daily max. dose of 90mg/kg/d is not exceeded


  • paracetamol is generally a very safe drug with few adverse effects and is well tolerated.
  • HOWEVER, in excessive dosing(s), fatal hepatotoxicity may occur
  • even normal doses may cause fatal liver failure if prolonged in susceptible patients (eg. malnourished or those with liver disease)
    • for example, see here (MJA 2007) for a fatal case where a 45yr old lady was ordered 1g paracetamol qid strictly for 8 days whilst nil by mouth for an abdominal surgical condition.

clinical stages of toxicity:

stage 1 (0-24hrs):

  • asymptomatic or mild GIT symptoms

stage 2 (24-48hrs):

  • resolution of N&V
  • RUQ pain & tenderness
  • progressive elevation of aminotransferases, bilirubin, & INR

stage 3 (48-96hrs):

  • progressive hepatic failure - jaundice, coagulopathy, encephalopathy

stage 4 (>96hrs):

  • death from fulminant hepatic failure or complete resolution by 3 months
paracetamol.txt · Last modified: 2016/05/16 13:51 by

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