A 35-year-old woman with a history of major
depressive disorder is brought into the ED by her
boyfriend. He believes she may have overdosed
on pain medication in an effort to hurt herself. He
gives you three medication bottles which he discovered
empty and states that they were nearly
full before leaving for work earlier that morning.
However, the timing of the ingestion is unclear. All
three of the bottles apparently held acetaminophen-
containing medications. Examination of the
patient reveals a tired-appearing woman complaining
of nausea and right upper quadrant
abdominal pain.
1. Depletion of which of the following is primarily
responsible for the hepatotoxicity being
experienced by the patient?
(A) N-acetyl-p-benzoquinone-imine
(NAPQI)
(B) taurine
© citrulline
(D) glutathione
(E) ornithine
2. Which of the following pharmacologic treatments
is most appropriate at this time?
(A) no pharmacologic treatment is
necessary
(B) naloxone
© flumazenil
(D) physostigmine
(E) N-acetylcysteine
3. Which of the following is the worst prognostic
indicator if present in this patient?
(A) arterial pH greater than 7.3
(B) arterial lactate greater than 3.5 mmol/L
© initiation of therapy 8 hours after acetaminophen
ingestion
(D) œprobable-risk of hepatotoxicity by the
Rumack-Matthew nomogram
(E) a history of chronic acetaminophen
abuse
successor, great.
D..
E..
B... ( i did wrong it too)
all of you love this explanation!
When acetaminophen is taken in normal doses, it is conjugated in the liver to harmless glucuronide and sulfate metabolites.
These metabolic pathways become easily overwhelmed in the setting of a large overdose, however. If this occurs, the cytochrome P450 system directs conversion of the excess acetaminophen to a compound called NAPQI, which is conjugated with glutathione to form a nontoxic mercapturate metabolite. Once glutathione stores are exhausted in the liver, however, the excess NAPQI combines with proteins within hepatic
cells causing hepatic cell death.
(Katzung, 2004, p. 36)
N-acetylcysteine should be administered as promptly as possible for treatment of acetaminophen overdose. It works by helping restore hepatic glutathione stores and by providing sulfhydryl groups that bind toxic metabolites. N-acetylcysteine is administered
orally in the form of an initial loading dose (140 mg/kg) followed by 17 doses (70 mg/kg
each) given every 4 hours. In addition to this oral therapy, the Food and Drug Administration
(FDA) approved 21-hour and 48-hour long intravenous treatment regimens in 2004.
Left untreated, acetaminophen overdose carries a significant risk for hepatic failure and subsequent death depending on the amount of acetaminophen ingested, the presence of any
preexisting liver disease, and interactions with any other medications that induce cytochrome
P450 enzyme activity.
Poor prognosis is associated with
elevated serum lactate levels (above 3.5 mmol/L),
acidemia (arterial pH less than 7.3),
renal failure,
and coagulopathy.
The Rumack-Matthew nomogram provides a means of determining
whether an individual falls into the possible-, probable-, or high-risk categories for developing
hepatotoxicity based on serum acetaminophen levels and the number of hours since ingestion.
Therapy with N-acetylcysteine is most effective if begun within 8 hours of the toxic ingestion but still has proven benefit if started within 24 hours.
(Harrison™s Internal Medicine online, Chap. 286
œToxic and Drug-induced Hepatitis.)