The toxic dose of acetaminophen is > 200 mg/kg in dogs.
In dogs, acetaminophen undergoes both toxic and nontoxic biotransformation in the liver, resulting in production of a byproduct para-aminophenol in the liver, which induces methemoglobinemia. This is a species specific anomaly in dogs and cats due to a deficiency in hepatic arylamine N-acetyltransferase activity.
Acetaminophen is conjugated with glucuronide and sulfate by transferase enzymes but only a small portion of a dose is converted to reactive metabolites by the cytochrome P-450-dependent mixed function oxidase system. The reactive metabolites formed may subsequently become conjugated with glutathione and excreted in the urine as nontoxic metabolites. Toxicity results if the active metabolite depletes glutathione stores.
Affected dogs invariably have a history of acetaminophen ingestion and following a brief interlude present with whole body tremors, weakness, tachypnea, tachycardia and stupor may be evident.
Mucous membranes are usually bluish and cyanotic and the tongue is often a grey-blue color. In rare cases, icterus has been noted following a single ingestion. Edema of the face and paws is frequently observed.
Diagnosis is based on presenting clinical signs together with blood samples which usually show evidence of dark brown-colored blood, hypoalbuminemia, elevated ALT and AST, and Heinz-body anemia. Urinalysis may reveal hemoglobinuria.
Supportive intravenous fluids and oxygen therapy are usually given to effect, and N-acetylcysteine is considered an antidote for this toxin, given at 140 mg/kg over a 6 - 8 hour interval.
Treatment with s-adenosyl-l-methionine as a glutathione donor has also showed promise when given at a loading dose of 40 mg/kg body weight orally, followed by a maintenance dose of 20 mg/kg once dailt for 7 days.
The use of sodium bicarbonate, ascorbic acid and S-adenosylmethionine may also help minimize the oxidative effects of acetaminophen.
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