or paracetamol) is the most popular over-the-counter analgesic and
is one of the most common toxic exposures reported to poison centers.
Acetaminophen is available as a sole agent or combined with a variety
of other medications prepared in many different forms, such as tablets,
capsules, gels, and liquids. Poisonings often occur because of the
erroneous belief that this medication is benign or because the victim
was unaware that acetaminophen was an ingredient in the ingested
preparation. During 2008, the American Association of Poison Control
Centers received reports of 71,328 exposures to acetaminophen combinations
and 80,845 exposures to acetaminophen alone.1 There
were 53 deaths attributed to isolated ingestion of acetaminophen
combinations and 69 deaths attributed to isolated acetaminophen
ingestions.1 The potential of an acetaminophen
overdose is indicated by the observation that acetaminophen (alone
and in combination) accounts for about 15% of the observed
fatalities seen with isolated ingestions of the top 25 categories
associated with a fatal outcome.1 Combining ED,
hospital, and poisoning databases, an estimated 450 deaths occur
each year in the U.S. due to acetaminophen overdoses, and approximately
100 of them are unintentional.2
The recommended dosing of acetaminophen is 650 to 1000 milligrams in
adults and 10 to 15 milligrams/kg in children, every 4
to 6 hours. The recommended maximum total daily dose is 4 grams
in adults and 75 milligrams/kg in children. After ingestion
of therapeutic doses, acetaminophen is rapidly absorbed from the
GI tract, and peak serum levels are usually achieved within 30 minutes
to 2 hours. In an overdose, peak serum levels are usually achieved
within 2 hours, but delayed absorption of acetaminophen is reported
following overdoses of preparations in which acetaminophen is combined
with propoxyphene or diphenhydramine, as well as those with altered
release kinetics such as extended-release preparations. In therapeutic
amounts, acetaminophen has virtually 100% bioavailability,
is approximately 20% bound to serum proteins, has a volume
of distribution of around 0.85 L/kg, and an elimination
half-life of approximately 2.5 hours. The therapeutic level for
the antipyretic effect of acetaminophen is between 10 to 20 micrograms/mL,
whereas the therapeutic level for the analgesic level is not established.
In therapeutic amounts, acetaminophen is primarily metabolized
by the liver through sulfation (20% to 46%) and
glucuronidation (40% to 67%), with <5% undergoing
direct renal elimination. Normally, a small percentage is also oxidized
by the cytochrome P-450 system to a reactive metabolite N-acetyl-p-benzoquinoneimine
(NAPQI), which is quickly detoxified by hepatic glutathione to a
nontoxic acetaminophen-mercapturate compound that is renally eliminated
Acetaminophen metabolism. A. After ingestion
of therapeutic amounts, predominant metabolism is via glucuronidation and
sulfation. The small amount of N-acetyl-p-benzoquinoneimine (NAPQI)
generated is metabolized by adequate glutathione stores to a nontoxic
compound. B. After ingestion of large amounts, glucuronidation
and sulfation are saturated, and an ...
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