metabolism
Ahmad Izzuddin Mohd Rosli
ACETAMINOPHEN
METABOLISM
Paracetamol is primarily metabolized in the
liver
We
look
this!
will
into
adding or unmasking
a hydroxyl group
PHASE 2: CONJUGATION
5%
A. MAJOR PATHWAY
uridine
diphosphoglucuronosyl
transferase
Cause
conjugation of
glucuronide group on
the acetaminophen
Glucuronide conjugate
(NON TOXIC)
eliminated
directly via
urine
90%
Enter our
body
converted
to
Cause conjugation of
sulphate group on the
acetaminophen
Sulphate conjugate
ELIMINATION
(NON TOXIC)
5%
enter CYP450
system
AT TOXIC DOSES
NAPQI production increase!
NAPQI
NAPQI
NAP
QI
NAPQI
Exceed
**********************************
inactivate
GLUTATHIONE
exceed
NAPQI
inactivate
GLUTATHIONE
AT TOXIC DOSES
Reactive quinone in NAPQI structure
highly succeptible to thiol nucleophilic
attack from the liver protein
glutathione
depletion cause
the reaction to
move to this
pathway
NAP
QI
Hepatic necrosis
NAPQI
Abundance of
toxic NAPQI
cause
Renal failure
But it
can be
revers
ed
using
Hepatic necrosis. toxic injury to the liver with sudden and precipitous onset,
Renal failure. kidneys fail to adequately filter waste products from the blood.
poisoning
Thank you