Page 403 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

370 SECTION | IV Drugs of Use and Abuse

VetBooks.ir NSAID metabolism (Talcott, 2006; Wallace et al., 1990; progress to erosive and, then, ulcerative lesions. The loca-
tion for gastric ulceration in the canine stomach is vari-
Verbeeck, 1990). Cimetidine given at a dose of 6 mg/kg
able; lesions can be near the pylorus, lesser curvature of
every 6 h caused decreased basal acid output in dogs by
30% 50%, and food induced output by 63% 71%. When the fundus or diffuse. Duodenal ulcers and perforations
12 mg/kg was used every 6 h, there was a 70% 80% have been reported in dogs, but can be influenced by pre-
decrease in basal acid output and complete suppression of disposing factors. Perforations are reported to occur in the
food-induced output (Boulay et al., 1986). Cimetidine is stomach, small intestine, or colon. Ulcers that erode
given to dogs at a dose of 5 10 mg/kg PO, SC, or slow mesenteric vasculature are rapidly lethal.
IV every 6 8h (Villar et al., 1998; Plumb, 2015). Similar Gastric ulcerations in the horse usually occur in the
dosing protocols are used in cats and ferrets. glandular mucosa adjacent to the margo plicatus (Collins
Ranitidine does not inhibit microsomal enzymes like and Tyler, 1984, 1985; Roder, 2004a). Linear-to-circular
cimetidine. However, Bersenas et al. (2005) found no sig- erosions were reported in the duodenums of horses dosed
nificant effect on gastric acid secretion in dogs dosed with phenylbutazone, and ulcers and erosions were found
with ranitidine. Ranitidine also decreases gastric blood throughout the small intestines. Ulcerative colitis of the
flow. It is given at a dose of 0.5 2.0 mg/kg PO, IV, or right dorsal colon is commonly seen in horses with
IM every 8 12 h in dogs, and 2.5 mg/kg IV or 3.5 mg/kg NSAID toxicosis. Fibrinonecrotic typhlocolitis was
PO in cats every 12 h (Plumb, 2015). Villar et al. (1998) reported by Collins and Tyler (1985).
recommend continuous treatment for 3 6 weeks. Papillary necrosis occurs with long-term NSAID
Famotidine increases intragastric pH in dogs better administration (Mazue ´ et al., 1982). The lesion is bilateral
than ranitidine. However, a 0.5 mg/kg dose of famotidine and the papillae are cavitated, yellow-green to orange,
given two to three times a day did not result in a pro- and demarcated from the medulla by hemorrhage. The
longed gastric pH increase (pH . 4) in dogs (Bersenas lesion is most severe at the poles. Microscopically, the
et al., 2005). Famotidine was found protective against papilla has undergone coagulative necrosis, with dilation
gastric hypoxia from reduced perfusion when used at a of the collecting ducts and loops of Henle. Interstitial
dose of 0.5 mg/kg IV in dogs given diclofenac (Hata fibrosis extends through the medulla and cortex in chronic
et al., 2005). Dogs are given 0.5 1 mg/kg famotidine PO cases (Gunson, 1983). This lesion has been reported in
or slow IV every 12 h. The dose for cats is 0.5 mg/kg, horses, dogs, cats, mice, rats, gerbils, hamsters, rabbits,
and 0.25 0.5 mg/kg is the dose for ferrets. Horses are desert mice, primates, and pigs (Brix, 2002). The lesion is
given 0.23 mg/kg IV or 1.88 mg/kg PO every 8 h or common in horses given phenylbutazone, but has also
0.35 mg/kg IV or 2.8 mg/kg PO every 12 h. been reported with flunixin, aspirin, and dipyrone
The prognosis for NSAID toxicosis is dependent on (Gunson, 1983). Papillary necrosis occurred in two of five
chronicity, dose, and clinical signs (Talcott, 2006). A study dogs dosed with piroxicam (Talcott, 2006).
by Wallace et al. (1990) found that seven out of seven dogs Interstitial nephritis, with multifocal or diffuse infil-
treated for chronic NSAID toxicosis recovered after 2 9 trates of lymphocytes, has been reported, as has vacuolar
days of hospitalization. The mean hospital stay was 6 days. degeneration of proximal and distal convoluted tubules
Gastrointestinal irritation and ulceration are reversible, but (Kore, 1990). Tubular nephritis with epithelial necrosis
perforation and peritonitis require immediate surgical inter- and regeneration has also been described (Mazue ´ et al.,
vention plus intensive medical management and have a 1982). Acute cortical necrosis due to NSAID toxicosis has
guarded prognosis. Renal effects, such as nephropathy, are been documented in small animals (Jones et al., 1992).
often reversible. Papillary necrosis is a permanent change, Lymphoid necrosis has been noted in dogs and a fer-
but well-tolerated. Loss of the long loops of Henle ret. Mild necrosis in the white pulp of the spleen was
decreases urine concentrating ability, but horses with renal described in the ferret (Cathers et al., 2000). Depletion
papillary necrosis usually appear clinically normal (Gunson, and necrosis of germinal centers was discovered in a dog,
1983; Roder, 2004a). Severe, acute cortical necrosis is asso- although circulating lymphocytes were within the refer-
ciated with irreversible renal failure. NSAID-induced coa- ence range.
gulopathies are reversible once the NSAID has been
eliminated. Dogs with idiosyncratic hepatic injury usually Aspirin and Other Salicylates
recover within 4 weeks (Albretsen, 2002).
This group, which constitutes the most extensively used
OTC drugs, includes acetylsalicylic acid, or aspirin, sodium
Postmortem Findings salicylate, bismuth subsalicylate, and diflunisal. Aspirin and
NSAID toxicosis is most commonly associated with gas- salicylates are NSAIDs with many characteristics similar to
trointestinal lesions in domestic animals. Mild lesions those of other NSAIDs, as described previously. Aspirin
include mucosal edema, irritation, and petechiation, which and salicylate also have certain unique properties. Clinical