paracetamol (acetaminophen)

introduction:

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
see paracetamol overdose - single ingestion and paracetamol overdose - multi-dose ingestion
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.

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