Tylenol (Acetaminophen) Toxicosis in Cats
Acetaminophen is the main ingredient
of Tylenol and several other non-aspirin pain relievers. It
possesses both analgesic and antipyretic effects. The feline
toxic dosage is 50-100 mg/kg. One regular-strength tablet
(325 mg) may be toxic to cats, and a second could be lethal.
One "extra strength" (500 mg) tablet can result in toxicosis.
The most common abnormalities observed upon physical examination
of cats are: increased respiratory rate, pale-muddy mucous
membranes, hypothermia, and tachycardia. Other signs are CNS
depression, anorexia, vomiting, swollen face and paws, salivation,
diarrhea, coma and death.
Cyanosis and pale-muddy mucous membranes
develop from methemoglobinemia within 3-12 hours after ingestion
of a toxic dose of acetaminophen. Hematuria and hemoglobinuria
may appear when blood methemoglobin levels exceed 20%. Laboratory
findings include anemia with a large number of Heinz bodies.
Death can occur within 18 to 36 hours when methemoglobin concentrations
exceed 50%.
Acetaminophen is metabolized to its highly
reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI) in
cells with P450 activity. In most species, excluding cats,
a majority of administered acetaminophen is excreted in the
urine as glucoronide and sulfate conjugates which are essentially
non-toxic metabolites. A small amount of acetaminophen is
normally metabolized to highly reactive intermediates which
are scavenged by glutathione and excreted. Once glutathione
stores are depleted, the reactive intermediates bind to intracellular
macromolecules resulting in cell death. Cats are relatively
deficient in activity of the enzyme glucuronyl transferase
which conjugates acetaminophen to glucuronic acid for excretion.
For a given dose of acetaminophen, less than 3% of acetaminophen
glucuronide is excreted by cats, while humans and dogs eliminate
50-60% as the glucuronide conjugate. Therefore, in cats a
relatively greater proportion of acetaminophen is available
and metabolized to reactive intermediate compounds. Cellular
stores of glutathione become rapidly depleted in the liver,
erythrocytes, as well as in other cells throughout the body.
Glutathione depletion leaves the cells unprotected from the
oxidizing effect of the toxic acetaminophen metabolite NAPQI.
In the majority of animals, including dogs
and humans, acetaminophen toxicity primarily causes damage
to the liver. However, while cats can and do have liver damage
associated with acetaminophen toxicosis, the primary manifestation
of toxicosis is severe methemoglobinemia leading to hemolysis
and methemoglobinuria.
Blood from animals with methemoglobinemia
is darker and browner than normal. Heinz bodies are formed
from the precipitation of damaged hemoglobin within the red
blood cell, which leads to increased osmotic fragility of
the erythrocyte and hemolysis.
Diagnosis is usually based on a history of
ingestion, appropriate clinical signs, methe-moglobinemia,
Heinz Body anemia, hemo-globinuria, and elevated serum activities
of liver enzymes.
Treatment for acute acetaminophen toxicosis
in cats include:
1) Induction of vomiting followed by
activated charcoal and a saline cathartic if ingestion is
recent (within 4-6 hours).
2) Oxygen therapy if there is severe
cyanosis.
3) Intravenous or oral administration
of acetylcysteine (140 mg/kg as a 5% solution initially,
followed by 70 mg/kg IV every 4 hours, for a total of 4
to 6 treatments). Acetylcysteine provides cysteine required
for increasing synthesis of glutathione.
4) Ascorbic acid (30 mg/kg orally) for
treatment of methemoglobinemia. Vitamin C should be given
every 6 hours as needed.
5) Fluid therapy for possible acidosis.
- by Darko Mladenovic, ECFVG
- edited by Stephen Hooser, DVM, PhD
|
