Page 395 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

362 SECTION | IV Drugs of Use and Abuse

VetBooks.ir treatment is delayed or exposure is unconfirmed. This and cats to inhibit acetaminophen metabolism through
Cimetidine has been recommended for use in dogs
treatment is most effective within 8 h of exposure; how-
inhibition of cytochrome P450 enzymes; however, the
ever, treatment within 24 h decreases mortality from liver
failure. N-acetylcysteine is sold in 10% and 20% solu- doses required for enzyme inhibition are higher than
tions. Twenty percent solutions are diluted 1:1 in normal doses used routinely (Sellon, 2006).
saline or a 5% 10% dextrose solution (MacNaughton, The time that elapses between exposure and treatment
2003; Plumb, 2015; Sellon, 2006). An initial dose of seems to be as, if not more, important in estimating the
140 mg/kg is given intravenously (IV) slowly. prognosis for survival. Most cats that survived were trea-
Alternately, the dose can be given orally if no vomiting is ted within 14 h of exposure, although one cat was not
evident and activated charcoal has not been given treated for 24 h. Most of the cats for which treatment was
recently. Doses of 70 mg/kg N-acetylcysteine should be delayed 17 or more hours postexposure died. There were
given IV or PO every 6 h thereafter for 48 h. A new drug, no differences in exposure dose between the group of
N-acetylcysteine amide, with greater bioavailability, has cats that died and those that survived. Cats with underly-
shown promise in experimental studies of acetaminophen ing disease most likely have a worse outcome than other-
toxicosis (Khayyat et al., 2016). wise healthy cats. The survival rate in dogs decreases if
SAMe is another possible sulfate source used to treat treatment is delayed more than 72 h (Sellon, 2006).
acetaminophen toxicosis in dogs and cats. Decreased hemo- Animals that were treated and survived usually recovered
lysis and overall improvement were reported in treated dogs within 48 h, and were hospitalized for 3 days (Aronson
(Wallace et al., 2002). Prevention of methemoglobin pro- and Drobatz, 1996).
duction in cats by SAMe has been inconsistent. The number
of Heinz bodies was lower and the packed cell volume Postmortem Findings
(PCV) remained higher in treated versus untreated experi-
mental cats (Webb et al., 2003; Sellon, 2006). Dogs are Icterus is a common finding secondary to acute hemolysis
or chronic cholestasis. Centrilobular necrosis occurs com-
given 40 mg/kg PO as their first dose and 20 mg/kg daily
monly in dogs, and has been described in cats, although
for 7 9 days thereafter. Protocols recommended for cats
necrosis is likely to be more diffuse in cats. Bile duct
include 180 mg/kg SAMe PO every 12 h for 3 days and
proliferation, vacuolar hepatocyte degeneration, and
90 mg/kg SAMe PO every 12 h for 14 days.
mononuclear cholangitis are reported in dogs with chronic
There are reports of sodium sulfate as a treatment for
liver injury. Subcutaneous edema extends from the head
acetaminophen toxicosis. This protocol decreased the
plasma half-life of acetaminophen in cats and increased along the fascial planes of the neck and thorax in some
the amount excreted as a sulfate conjugate, similar to affected cats and dogs, and can affect the conjunctiva
N-acetylcysteine (Savides and Oehme, 1985). Severity (Allen, 2003).
and duration of clinical signs and methemoglobin concen-
trations were decreased in treated animals, and glutathi- Nonsteroidal Antiinflammatory Drugs
one concentrations rebounded faster than in untreated cats
(Villar et al., 1998). Sodium sulfate was given as a 1.6% NSAIDs are defined as “compounds that are not steroidal
solution at a dose of 50 mg/kg IV every 4 h for six and that suppress inflammation” (Boothe, 2001). These
treatments. drugs have antithrombotic actions when taken at low
Ascorbic acid and methylene blue are commonly used doses, relieve minor pain and pyrexia at moderate doses,
to reduce methemoglobin to hemoglobin. Ascorbic acid and have antiinflammatory effects at higher doses (Rubin
causes nonenzymatic reduction of methemoglobin, but is and Papich, 1990; Boothe, 2001). NSAIDs are commonly
slow-acting. Ascorbic acid is given at a dose of 30 mg/kg used to treat orthopedic problems in dogs (Wallace et al.,
PO every 6 h for six or seven treatments. Methylene blue 1990). About 8% of all human- and veterinary-related
has a rapid onset, but can induce hemolytic anemia in calls to the Illinois Poison Control Center were reported
cats, making it a risky choice; still, methylene blue has to involve NSAIDs, most commonly aspirin, ibuprofen,
been used successfully for short-term management of naproxen, piroxicam, indomethacin, and phenylbutazone.
feline methemoglobinemia. Use of methylene blue con- Out of those calls, 70% of the nonhuman animal calls
currently with N-acetylcysteine in cats should be avoided. were for dogs and 25% for cats (Kore, 1990). NSAID tox-
Supportive and symptomatic therapy for acetamino- icosis can be caused by a single large dose or multiple
phen toxicosis includes administration of oxygen to smaller doses (Albretsen, 2002).
animals with methemoglobinemia. Transfusion or hemo- There are more than 30 commercially available NSAIDs
globin replacement is needed in cases of severe anemia (Mazue ´ et al., 1982). They are classified based on their
(Murphy, 1994; Sellon, 2006). Fluid therapy is aimed at structure into the carboxylic acid group, which includes
improving hydration, electrolyte balance, and pH. salicylic acid derivatives, acetic acid derivatives, fenamates,