Page 391 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

358 SECTION | IV Drugs of Use and Abuse

VetBooks.ir information you provide for adverse events reporting to common clinical situation results from the owner medicat-
ing their animal without the benefit of a veterinarian’s
the Food and Drug Administration (FDA). More informa-
advice and supervision (Hjelle and Grauer, 1986; Aronson
tion on adverse event reporting can be found at the FDA
website: http://www.fda.gov/cvm/adetoc.htm. Any mate- and Drobatz, 1996). One report documents severe poison-
rial remaining in the container can be analyzed to verify ing in a kitten that had played with an empty acetamino-
that the contents are as expected (Brumbaugh, 2001). phen tablet container (Allen, 2003). Although the
Serum, urine, vomitus, and gastric lavage (liver, kidney, hepatotoxic effects of acetaminophen have been described
and GI content for postmortem) should also be saved for in many species, the hematotoxic effects have only been
analysis if it is unclear what the animal has ingested. documented in cats and dogs (McConkey et al., 2009).
Early gastrointestinal decontamination is sometimes help-
ful in the asymptomatic animal, and can involve emetics Toxicity
or gastric lavage and instillation of activated charcoal and
Individual differences in sensitivity are reported within
cathartics depending on the situation. If drugs are used
and across species (Webb et al., 2003), but the use of
topically, removal with a mild detergent bath is usually
acetaminophen is always contraindicated in cats due to
beneficial. Careful monitoring and maintenance of body
their extreme sensitivity (Jones et al., 1992; Roder,
temperature is required after bathing, and bath towels
2004a; Villar et al., 1998; Wallace et al., 2002). Clinical
may be warmed by tumbling in a heated clothes dryer to
signs of acetaminophen toxicosis, up to and including
help prevent hypothermia.
death, have been reported in cats at doses of 10 mg/kg
(Aronson and Drobatz, 1996); however, most poisonings
ANALGESICS are associated with doses of 50 mg/kg and greater
(Murphy, 1994; Allen, 2003; MacNaughton, 2003; Roder,
According to Jones et al. (1992), about 5% of dog- and
2004a; Sellon, 2006). Villar et al. (1998) reported 50%
cat-related calls to one poison control center were in
methemoglobinemia within 4 h in cats dosed with
response to analgesic ingestion; nearly 80% involved
120 140 mg/kg acetaminophen. One of four cats dosed
dogs. Analgesics are listed every year on the ASPCA
with 143 mg/kg died. One regular acetaminophen tablet
Animal Poison Control Center and the Pet Poison
contains 352 mg of the active ingredient, and an extra-
Helpline’s websites among the most common causes of
strength tablet contains 500 mg.
poisonings in domestic animals. Commonly used OTC
The recommended oral dose for acetaminophen in
analgesics include acetaminophen and nonsteroidal antiin-
dogs is 15 mg/kg every 8 h, or 10 mg/kg every 12 h for
flammatory drugs (NSAIDs), such as aspirin, ibuprofen,
long-term dosing (Plumb, 2015). Toxicosis has been
naproxen, and ketoprofen. Aspirin shares many properties
reported at a dose of 46 mg/kg (Sellon, 2006), although
with other NSAIDs, but will be addressed separately due
doses of 100 mg/kg or greater are more likely to be asso-
to some of its unique features.
ciated with clinical signs (Jones et al., 1992; Boothe,
2001; Roder, 2004a). Most dogs dosed with less than
Acetaminophen 460 mg/kg will recover (Villar et al., 1998). Doses over
460 mg/kg in dogs are associated with methemoglobine-
Acetaminophen is an analgesic and antipyretic, although
mia, and deaths have occurred (Schlesinger, 1995; Villar
it does not have the antiinflammatory properties of
et al., 1998; Wallace et al., 2002); a dose of 900 mg/kg
NSAIDS (Hjelle and Grauer, 1986). Acetaminophen
caused “fulminant liver failure” (Boothe, 2001). Doses
is a metabolite of the historic drug phenacetin.
greater than 1 g/kg (1000 mg/kg) are reported to cause
Acetaminophen is found in a variety of OTC pain relie-
unconsciousness and cyanosis within hours and death
vers, and is often combined with other drugs in cold, flu,
within 12 h (Villar et al., 1998).
and allergy medications (Roder, 2004a). Common brand
names in the United States include Tylenol and Anacin-3.
Acetaminophen is sold under the name Paracetamol in Toxicokinetics
Australia and Great Britain. Overdose is a common cause After ingestion, acetaminophen is rapidly absorbed in the
of morbidity in humans, with almost 80,000 hospital stomach and small intestine (Schlesinger, 1995; Wallace
emergency room visits per year due to acetaminophen et al., 2002). Peak plasma concentrations occur 4 h after
hepatotoxicosis. Acetaminophen toxicosis in domestic ingestion in cats (Rumbeiha et al., 1995). Circulating
animals is most commonly reported in cats (Rumbeiha acetaminophen is minimally bound to plasma protein and
et al., 1995). Clinical acetaminophen toxicosis is usually widely distributed. The therapeutic plasma concentration
associated with a single exposure, although adverse of acetaminophen in a dog is near 30 μg/mL, and toxico-
effects as a result of multiple dosing have been reported sis is associated with concentrations of 300 μg/mL and
(Hjelle and Grauer, 1986; Villar et al., 1998). The most greater.