30 DRUG METABOLISM
Case history
A 46-year-old woman is brought to the hospital Accident
and Emergency Department by her sister, having swal-
lowed an unknown number of paracetamol tablets washed
down with vodka six hours previously, following an argu-
ment with her partner. She is an alcoholic and has been
taking St John’s wort for several weeks. Apart from signs
of intoxication, examination was unremarkable. Plasma
paracetamol concentration was 662μmol/L (100 mg/L).
Following discussion with the resident medical officer/
Poisons Information Service, it was decided to administer
N-acetylcysteine.
Comment
In paracetamol overdose, the usual pathway of elimination
is overwhelmed and a highly toxic product (N-acetyl benzo-
quinone imine, known as NABQI) is formed by CYP1A2, 2E1
and CYP3A4 metabolism. A plasma paracetamol concentra-
tion of 100 mg/L six hours after ingestion would not usually
require antidote treatment, but this woman is an alcoholic
and is taking St John’s wort and her hepatic drug-
metabolizing enzymes (CYP1A2, CYP3A4 and probably
others) will have been induced, so the paracetamol concen-
tration threshold for antidote treatment is lowered (see
Chapter 54). N-Acetylcysteine is the specific antidote, as it
increases reduced glutathione which conjugates NABQI
within hepatocytes.FURTHER READING AND WEB MATERIAL
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