Page 400 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 367

VetBooks.ir (Albretsen, 2002; Roder, 2004a; Talcott, 2006); approxi- been associated with low-dose NSAID exposure in Old
World vultures (Fourie et al., 2015).
mately one-third of these cases were in Labrador
Transient increases in liver enzymes are frequently
retrievers.
Cartilage degeneration has been reported in mice seen in NSAID overdose in small animals. Severe hepa-
given aspirin, phenylbutazone, indomethacin, ibuprofen, totoxicosis is not common in NSAID-intoxicated small
and naproxen (Isaacs, 1996). Anaphylactic reactions have animals, although it has been reported in a dog given
been reported, but hypersensitivity to NSAIDs is rare. naproxen (Kore, 1990; Lees et al., 1991; Isaacs, 1996)
This problem is has been documented in dogs due to and as an idiosyncratic reaction to carprofen (Albretsen,
phenylbutazone administration (Rubin and Papich, 1990; 2002). Clinical signs include anorexia and weight loss,
Lees et al., 1991; Isaacs, 1996). vomiting, lethargy, icterus, ascites, and coagulopathy.
Increased bleeding times are rarely reported in domestic
animals (Murphy, 1994). Prolonged gestation and
Clinical Signs teratogenesis have been seen experimentally (Lees
The most commonly reported clinical signs associated et al., 1991).
with NSAIDS in dogs and cats are gastrointestinal distur-
bance, renal insufficiency, lethargy, and death; gastroin-
testinal disturbance, particularly vomiting and diarrhea, Clinical Chemistry
but also including melena, colitis, abdominal pain, and Approximately one-quarter of gastroduodenal ulceration
icterus, are far more frequent than the others and most cases in dogs present with microcytic hypochromic ane-
likely underreported (Hunt et al., 2015; Montiero-Steagall mia due to chronic blood loss (Stanton and Bright,
et al., 2013). Use of NSAIDs is the most common predis- 1989); acute blood loss is uncommon. Individuals with
posing factor to gastrointestinal ulceration in dogs requir- acute blood loss present with rapid deterioration, nor-
ing emergency intervention (Montiero-Steagall et al., mocytic and normochromic anemia, a normal albumin
2013). Clinical signs do not always correlate well with to globulin ratio, and evidence of regeneration (Stanton
the severity of the lesion, probably due to the analgesic and Bright, 1989; Wallace et al., 1990). Peracute hemor-
effect of NSAIDs. The asymptomatic ulcer rate among rhage is rare, and occurs when a mesenteric blood vessel
NSAID users is estimated at 50% (Isaacs, 1996). Animals becomes eroded in the area of ulceration. Such a com-
with gastric perforations usually present with a distended plication would be rapidly lethal and not allow time for
abdomen due to effusion, dehydration, pyrexia, collapse, a regenerative response. Increased PCV has been seen
pallor, and abdominal pain (Godshalk et al., 1992; in horses with dehydration secondary to diarrhea
Talcott, 2006). (Collins and Tyler, 1985).
Lower gastrointestinal tract effects can include Fecal occult blood is unreliable. It can be negative for
protein-losing enteropathy, most common in horses, and low-level blood loss or positive if red meat was fed
stricture formation; horses with hypoproteinemia often within 72 h of testing (Talcott, 2006). Hypoalbuminemia
have secondary edema (Collins and Tyler, 1984, 1985). has been observed with gastrointestinal ulcers and
Endotoxemia and shock have been noted in horses sec- protein-losing enteropathy secondary to NSAID use.
ondary to gastrointestinal ulceration. Both albumin and globulin concentrations are decreased.
Analgesic nephropathy occurs in humans, has been Coagulation profiles reveal poor platelet aggregation,
reported in dogs given naproxen and, more recently, in thrombocytopenia, and increased bleeding times.
cats given meloxicam or accidentally exposed to flurbi- Serum chemistry reveals increased ALT, AST, ALP,
profen (Isaacs, 1996; Boothe, 2001; Dyer et al., 2009; and bilirubin (Albretsen, 2002; Roder, 2004a). A mild,
Anonymous 2015). Chronic use of NSAIDs in high transient rise in liver enzymes often occurs during
doses appears to be a predisposing factor, except with the first week of NSAID administration. Elevated
flurbiprofen. It is likely that preexisting kidney disease BUN indicates nephropathy. Phosphorus, calcium, and
in cats predisposes them to NSAID-associated renal potassium are usually also elevated. Animals with renal
insufficiency, making it critical to assess hydration sta- damage due to NSAIDs present with isosthenuria, hema-
tus before prescribing NSAIDS (Hunt et al., 2015). turia, and proteinuria. Ketonuria and pyuria have also
Clinical signs are evident 2 weeks or many months after been reported. Horses on chronic, high-dose phenylbuta-
chronic dosing or, sometimes, after single, very high zone therapy had normal lymphocyte counts, with a left
doses. Acute onset of oliguric renal failure has been shift due to neutrophil loss into the gastrointestinal tract.
described (Kore, 1990; Villar et al., 1998; Roder, Increased serum glucose concentrations were attributed
2004a). Animals may present with polyuria and poly- to endotoxemia. Hypokalemia and hyponatremia are
dipsia, dehydration, oral ulceration, and uremic coma commonly seen in horses with diarrhea (Collins and
(Mazue ´ et al., 1982). Renal failure and visceral gout has Tyler, 1985).