paracetamol
Table of Contents
paracetamol (acetaminophen)
see also:
introduction:
- 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
pharmacology:
- 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
actions
- 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
dosage
- 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
toxicity
- 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 127.0.0.1