Paracetamol (Acetaminophen) Poisoning
Mechanism:
Acetaminophen (APAP) hepatotoxicity occurs through formation of the noxious N-acetyl-para-benzo-quinone imine (NAPQI) metabolite, which is present in excessive quantities, as augmented by features of glutathione (GSH) depletion, oxidative stress and mitochondrial dysfunction leading to depletion in adenosine triphosphate (ATP) stores.
Other mechanisms of hepatotoxicity include the formation of toxic free radicals, such as peroxynitrite, from the reaction of superoxide and nitric oxide, subsequently forming nitrotyrosine adducts inside the mitochondria.
toxic if > 8 to 10 grams; fatal if ingested 12-15 grams
If definite toxic amount ==> N-acetylcysteine
If amount is uncleard -=> do drug level
If delayed (> 24hrs), No therapy
Toxic dose = 150mg/kg (75mg/kg if malnourished) or 12g in adults may be fatal (10-15g ~ 20-30 tablets)
Max. Therapeutic dose = 4g/day
Acute poisoning:
1 hr = larvage + activated Charcoal
4 hr = Paracetamol level
8 hr = N-acetylcysteine (within 8 hr, effectiveness is the same, afterwards it declines); alternative – Methionine
12 hrs = Review and repeat INR q12h
24 hr = review with results (see criteria for transfer)
48 h = review (if INR normal and pt stable, possible home)
N-acetylcysteine