see also:

• pain, analgesia and analgesics
• paracetamol overdose

• 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
• its analgesic actions appear to require CB1 receptors ¹⁾
• a secondary metabolite N-arachidonoylaminophenol (AM404) of paracetamol has multiple effects on cannabinoid signaling including blockade of anandamide uptake; inhibition of fatty acid amide hydrolase (FAAH), an enzyme that metabolizes the eCB arachidonoylethanolamine (anandamide); and indirect activation of TRPV110 and/or cannabinoid receptors.
• inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol (2-AG) which makes one of the endogenous cannabinoids resulting in reduced CB1 activation which may have a role in nociception ²⁾
• inhibits pain impulses peripherally
• inhibits brain prostaglandin synthetase
• may also:
  • decrease empathy ³⁾
  • 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
• see paracetamol overdose
• 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.
    • https://www.abc.net.au/news/2024-09-18/paracetamol-overdose-death-canberra-hospital-liver-failure/104362348 - ACT coroner finds 73yr old lady died from excessive IV paracetamol doses given to her in hospital over 5 days in 2021 as her weight of 39kg was not taken into account

• asymptomatic or mild GIT symptoms

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

• progressive hepatic failure - jaundice, coagulopathy, encephalopathy

• death from fulminant hepatic failure or complete resolution by 3 months