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It is the one of the most commonest toxic exposures reported to poison centre.

Pharmacology

• It is primarily metabolized by liver through sulfation (20 – 46%) & glucoronidation (40 – 67%) with <5% undergoing renal elimination.

• Normally a small percentage is also oxidised by the cytochrome P-450 system to a reactive metabolite N- acetyl-p-benzoquinoneimine (NAQPI) which is detoxified by hepatic glutathione to a non toxic acetaminophen-mercapturate compund that is renally eliminated.

• Acetaminophen overdose, hepatic metabolism through glucorindation & sulfation may be saturated & a large proportion of acetominophen is metabolised by cytochrome P-450 to NAQPI depleting intracellular glutathione.

• When hepatic stores of glutathione decrease to <30% of normal ,NAPQI binds to other hepatic macromolecule and hepatic necrosis ensues.

DOSE : Max: Adult dose :4grams/day; Childrens : 75mg/kg.

CLINICAL FEATURE

DIAGNOSIS

• A toxic exposure is suggested when an adult ingest >10gm or 200mg/kg as a single ingestion or over a period of 24hrs.

• >6grms or >150mg/kg per 24hrs for a period of atleast two consecutive days.

Rumack- Mathew Normogram

• This normogram was derived from a retrospective analysis of acetominophen overdose patients & their clinical outcome.

• Here the acetominophen drug levels in plasma is plotted against time duration of post ingestion.

• Original normogram line separating possible toxicity from unlikely toxicity was based on a 4hr acetominophen level of 200mcg/ml but was modified by US FDA by moving the line to 150mcg/ml to increase the safety margin.

• The normogram applies to an acetominophen level obtained after a single exposure & during the window between 4 hrs & 24hrs post ingestion.



TREATMENT

• Activated charcoal PO or through NG tube.

• Acetyl Cysteine

• MOA

  • In early stage (<8hrs) acetylcysteine averts toxicity by preventing the binding of NAPQI to hepatic macromolecules. It may act as glutathione precurosor or a substitute, a sulfate precursor or it may directly reduce NAPQI back to acetaminophen.

  • In established acetaminophen toxicity or >24 h it acts an antioxidant, decreasing neutrophil infiltration , improving microcirculatory blood flow or increasing tissue oxygen delivery & extraction.

  • If treatment is initiated within 8hrs following acute ingestion it is considered 100% effective.

• Availability & compatibility

  • Oral preparation :It is available as 10% or 20% at is diluted to a strength of 5% in a fruit juice or soft drinks.

  • Parenteral preparation is available as a 20% solution & is given as 2% dilution through peripheral vein. Compatible with 5% D or NS.

• Administration

 Fulminant Hepatic failure

• Acetaminophen toxicity is the no. one cause for liver failure in 39 -46% of cases.



Kings college criteria for liver transplantation.