Cats are great patients because they are less likely to ingest large amounts of bad stuff just because. However, their unique
metabolism presents other challenges as it contributes to the toxicities that we do see in cats and changes, often lowering,
the toxic dose we can expect. Also, substances that are safe in other species can be deadly in cats. The substances discussed
are by no means complete, but do address the most common toxicities. Even with the oldies still on our list, there may be
some new information which helps further define or treat the toxicity.
Acetominophen is a (paracetamol) is a synthetic non-opiate derivative of p-aminophenol that can produce both hepatotoxicity
and hematotoxicity, specifically, methemoglobinemia. Although the majority of acetaminophen is conjugated with sulfate and
glucuronide to form inactive metabolites, a small amount is processed via the cytochrome P450 enzyme system to form N-acetyl-p-benzo-quinone
imine (NAPQI). This intermediary metabolite is then conjugated with glutathione to an inactive product. Because NAPQI is
highly reactive it can cause hepatocellular damage once glutathione has been depleted.
A unique feature of acetaminophen toxicity in cats, and dogs to a lesser degree, however, is methemoglobinemia. A recent
study determined that a different metabolite may be responsible for this hematotoxicity that is not present in other species.
This metabolite, para-Aminophenol (PAP), is conjugated with glutathione and N-acetyl to detoxify it. The enzyme, N-acetyltransferase,
is deficient is both cats and dogs resulting in the hematotoxicity in these two species.As little as 10 mg/kg can result in
toxicity in cats. A regular strength Tylenol is 325 mg (extra strength tablets are 500 mg), children's suspension liquid
is 32 mg/ml, and infant's suspension liquid is 100 mg/ml. By way of comparison, a dose of 100 mg/kg in dogs is required for
hepatotoxicity and 200 mg/kg to produce methemoglobinemia.
Clinical signs of methemoglobinemia accompanied by hepatotoxicity in cats include increased respiratory rate, pale-muddy mucous
membranes, hypothermia, and tachycardia. Other signs are CNS depression, anorexia, vomiting, facial edema and edema of the
extremities, salivation, diarrhea, coma and death. Heinz body anemia, hemoglobinuria and hematuria as methemoglobin levels
rise in the bloodstream. Elevated liver enzymes will occur if hepatotoxicity is present. Death occurs within hours after
methemoglobin levels reach greater than 50%.
The goals of therapy are to:
1. Scavenge the reactive metabolites by replenishing glutathione: N-acetylcysteine (NAC) [5% solution PO or IV (using
a bacteriostatic filter): loading dose of 140 mg/kg, then 70 mg/kg every q 4 h for at least 3-5 treatments]. Ascorbic Acid
[30 mg/kg TID-QID PO or IV] for additional anti-oxidant scavenging can also be given.
2. Slow metabolism of parent substance to reactive metabolite: Cimetadine [5-10 mg/kg TID-QID PO or IV] interferes with
the P450 enzyme system.
3. Protect the liver from oxidant damage: SamE [180 mg BID PO x 3 days then 90 mg BID x 14 days – protocol from recent
study (Webb et al, 2003)]
Though methylene blue can be used to treat methemoglobinemia, it causes Heinz body anemia in cats and, therefore, should not