Page 394 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 361

VetBooks.ir tachycardia and tachypnea have also been reported includes elevated prothrombin time (PT), partial thrombo-
plastin time (PTT), and progressively decreased serum
(Roder, 2004a; Sellon, 2006; Stewart et al., 2016). Mild
cholesterol albumin concentrations (Sellon, 2006). Forty-
cases usually recover in another 2 3 days, but severe
cases progress to icterus and death, usually within 4 days one percent of cats presenting for acetaminophen
(Murphy, 1994; Sellon, 2006). toxicosis had hypocholesterolemia and 12% had hypoal-
Methemoglobinemia also occurs in dogs after ingest- buminemia (Aronson and Drobatz, 1996). Hemoglobinuria
ing high doses of acetaminophen, and is more likely to and hematuria have been observed in dogs and cats with
cause death than is liver failure. Methemoglobinemia usu- acetaminophen toxicosis.
ally occurs within 12 h of ingestion, but some dogs present
after 48 h. Doses of 200 mg/kg acetaminophen PO con-
verted 18.8% of hemoglobin to methemoglobin in dogs; Diagnosis and Management
500 mg/kg produced 51.5% methemoglobinemia (Hjelle Diagnosis of acetaminophen poisoning is usually based
and Grauer, 1986). Signs reported included cyanosis, brown on a history of clinical exposure and appropriate clinical
blood, brown urine, tachypnea, tachycardia, lethargy, and signs. Plasma, serum, and urine can be tested for acet-
recumbence (Schlesinger, 1995; Wallace et al., 2002; aminophen at human hospitals and some veterinary labo-
MacNaughton, 2003; Stewart et al., 2016). Hemolysis, ane- ratories to confirm the diagnosis. However, test results are
mia, icterus, and shock have been described. Several authors usually not available for hours or days, and acetamino-
report pigmenturia. Occasionally, signs of methemoglobine- phen toxicosis presents as an emergency, thus treatment
mia occur in acetaminophen-intoxicated dogs in the absence should be initiated immediately.
of clinically evident liver damage. Facial edema, keratocon- If the animal presents within 6 h of ingestion, decon-
junctivitis sicca, and edema of the forelimbs or paws have tamination measures can be instituted to prevent further
been observed in dogs (Stewart et al., 2016). absorption. Emetics can be used in the alert animal within
a couple of hours of ingestion. However, if large doses
were ingested, gastric lavage of the anesthetized, intu-
Clinical Chemistry bated animal is more likely to be appropriate. Activated
Methemoglobinemia and hemolysis are noted, especially charcoal and a cathartic such as sorbitol are given to pre-
in cats. Whole blood exposed to air appears brown. vent further absorption.
Heinz bodies in cats and dogs are evident on blood Antidotal therapy must be initiated as soon as possible
smears stained with new methylene blue. Heinz bodies in animals suspected of ingesting a toxic dose of acet-
occur within 3 days of dosing (Webb et al., 2003), and aminophen. Antidotal therapy involves use of sulfate
were evident in 12% of accidentally exposed cats sources to bind the active metabolites and enhance glutathi-
(Aronson and Drobatz, 1996). Anemia occurred in 75% one production. Several sulfur donors are available, and
of cats (Aronson and Drobatz, 1996), and has been include N-acetylcysteine, S-adenosyl methionine (SAMe),
reported in dogs (Schlesinger, 1995; Wallace et al., and sodium sulfate. N-acetylcysteine therapy is the most
2002; MacNaughton, 2003). In addition to Heinz bodies, accepted treatment for acetaminophen toxicosis. Additionally,
ghost cells, nucleated erythrocytes, eccentrocytes, and antioxidants can be used to reduce methemoglobin.
reticulocytes have been reported in affected dogs N-acetylcysteine is a glutathione precursor. N-acetyl-
(Stewart et al., 2016). Hyperbilirubinemia occurred cysteine acts as source of sulfhydryl groups to be used for
within 48 h of acetaminophen ingestion in cats, and has phase II sulfate conjugation or for glutathione production
been reported in dogs with hemolysis (Schlesinger, (Hjelle and Grauer, 1986; Savides and Oehme, 1985;
1995; Sellon, 2006). Evidence of regeneration has Villar et al., 1998). N-acetylcysteine is hydrolyzed to
been reported in dogs 2 11 days after acetaminophen L-cysteine by deacetylase enzymes. Use of N-acetylcys-
ingestion. teine promotes conjugation of acetaminophen metabolites
Hypoglycemia, mild hyperbilirubinemia, elevated in cats. Rumbeiha et al. (1995) reported a 50% decrease
ALT, ALP, blood urea nitrogen (BUN), creatinine, and in the plasma half-life of acetaminophen in cats treated
CK were the changes reported in a dog that had ingested with N-acetylcysteine, and Savides and Oehme (1985)
acetaminophen (Rumbeiha et al., 1995; Webb et al., reported an increase in the total fraction excreted as a sul-
2003; Sellon, 2006). This change was reported by fate conjugate. Cats treated with N-acetylcysteine have a
Aronson and Drobatz (1996) in 35% of exposed cats. more rapid recovery of blood GSH concentrations than
Increased ALT in dogs is a direct result of toxic hepatic untreated cats. N-acetylcysteine decreased the half-life of
injury, though hypoxic injury may contribute, and occurs methemoglobin in the blood of cats from more than 10 to
within 24 h of acetaminophen ingestion. Increased aspar- 5 h and prevented anemia.
tate transaminase (AST) and alkaline phosphatase (ALP) N-acetylcysteine therapy should be initiated in any
activities are reported. Evidence of severe liver damage suspected case of acetaminophen toxicosis, even if