Page 402 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 369

VetBooks.ir than 30% of the blood volume, a PCV less than 20%, been reported at discontinuation of omeprazole therapy
(Driman et al., 1995).
plasma protein less than 3.5 g/dL, or continued blood loss
Sucralfate is an aluminum salt of sucrose sulfate. This
are possible indications for transfusion (Talcott, 2006);
vitamin K 1 is given to aid coagulation (Kore, 1990). drug complexes with exposed proteins on the surface of
Perforating ulcers are a surgical emergency. gastric ulcers, specifically fibrinogen and albumin, and
Gastrointestinal protectants are typically used in acts as a direct mucosal protectant. Sucralfate has five
NSAID overdose cases to prevent or heal gastric ulcera- times as much affinity for damaged mucosa as it does for
tions. Gastric pH must be maintained above 3 for 18 20 h normal mucosa (Villar et al., 1998). Sucralfate also
a day for effective healing, and above 4 in critically ill adsorbs pepsin and bile acids. This drug is believed to
patients. Gastric pH above 4 inhibits fibrinolysis and the promote bicarbonate and mucus secretion by the gastric
activity of pepsin. Gastric pH must be above 6 to promote mucosa. Sucralfate is equally as effective as cimetidine at
platelet aggregation and prevent clot dissolution, therefore reducing discomfort and promoting ulcer healing. Dogs
allowing hemostasis. Gastric secretion is variable in bea- given sucralfate to treat gastric ulcers, with and without
gles, which can have a pH of pH of 1.30 under normal concurrent cimetidine treatment, had completed healing
conditions and 4.44 if fasted (Bersenas et al., 2005). of the gastric mucosa within 9 days. Sucralfate can be
Therefore, simply withholding food benefits the patient by used alone if gastric hyperacidity is not suspected
decreasing gastric acid secretion and minimizing emesis. (Wallace et al., 1990). If used with cimetidine, dosing
Treatment with antacids such as magnesium hydroxide should be staggered or cimetidine should be given by a
(milk of magnesia) or aluminum hydroxide is probably parenteral route because sucralfate interferes with gastro-
adequate for animals exposed to low NSAID doses. intestinal absorption of cimetidine (Wallace et al., 1990).
Antacids require dosing every 2 4 h, and sometimes pro- Cimetidine should be given 1 h before a meal. Dogs are
duce changes in fecal consistency (Wallace et al., 1990). dosed every 8 h. Dogs weighing .20 kg are given 1 g per
Products containing bismuth subsalicylate (Pepto Bismol dose, and smaller dogs are dosed with 0.5 g (Murphy,
and Kaopectate) should be avoided because salicylate acts 1994; Albretsen, 2002; Plumb, 2015). Cats are given a
as an NSAID. total of 0.25 0.5 g every 8 12 h, and ferrets are given
Misoprostol is a long-lasting synthetic analog of 75 mg/kg four to six times a day, preferably 10 min
PGE 1 . It is the only agent that consistently prevents and before feeding. Foals are given 1 2 g PO two to three
treats NSAID-induced gastric and duodenal ulcers (Isaacs, times daily.
1996). When given concurrently with aspirin, misoprostol H 2 histamine receptor antagonists, including cimeti-
prevented gastric ulcers in dogs (Villar et al., 1998). Dogs dine, ranitidine, and famotidine, are routinely used to treat
given NSAIDs and misoprostol had less gastrointestinal NSAID-induced gastric ulcers. Histamine stimulates
hemorrhage, less vomiting, and less mucosal ulceration gastric parietal cells to secrete hydrogen ions through an
1
1
on endoscopy than dogs given NSAIDs only (Talcott, H /K -ATPase pump. Acetylcholine, gastrin, and hista-
2006). Misoprostol is believed to protect renal function in mine stimulate this proton pump. H 2 inhibitors only block
domestic animals and be chondroprotective in pigs the histaminic effect on parietal cells, but cause significant
(Isaacs, 1996). At high doses, misoprostol can cause diar- inhibition of gastric acid secretion nonetheless (Bersenas
rhea, and use of this synthetic PG is contraindicated in et al., 2005). H 2 inhibitors are likely to suppress clinical
pregnant animals (Villar et al., 1998). Dogs can be given signs associated with unhealed ulcers (Talcott, 2006).
1 5 μg/kg misoprostol PO every 8 h (Plumb, 2015). Cimetidine has been commonly used to treat and pre-
Proton pump inhibitors suppress gastric acid secretion vent NSAID-induced ulcers. Cimetidine is believed to
1 1
by inhibiting the H /K -ATPase pump in gastric parietal decrease gastrointestinal discomfort, and does decrease
cells (Walan et al., 1989; Villar et al., 1998). Omeprazole gastric acid secretion (Boulay et al., 1986; Isaacs, 1996).
and pantoprazole are proton pump inhibitors (Bersenas Cimetidine has not been proven to be effective with
et al., 2005). Omeprazole has been used successfully in continued NSAID use, and did not prevent gastric ulcer
humans and dogs to treat gastric ulcer. Bersenas et al. formation when used concurrently with aspirin.
(2005) found that 2 mg/kg omeprazole PO given to dogs Cimetidine is more useful when NSAID administration
twice per day kept their gastric pH from going below 3 has ended and, possibly, after a single large dose (Kore,
for 90.9% of the day, and kept the gastric pH above 4 for 1990). Gastric acid production is dependent on local circu-
78.3% of the day, although one in six dogs vomited. lation, which provides oxygen and energy. Cimetidine
Omeprazole remains biologically active for nearly 24 h decreases gastric blood flow, which contributes to
and only need be given once daily. Plumb (2015) lists the decreased mucosal alkalinity (Cheung and Sonnenscheine,
canine daily dose as 0.5 1.0 mg/kg PO, and the feline 1983). Reduced circulation also contributes to tissue hyp-
dose as 0.7 mg/kg. Villar et al. (1998) recommend a 3- to oxia. Cimetidine is known to inhibit hepatic cytochrome
4-week treatment protocol. Rebound acid secretion has P450 enzymes and, therefore, could decrease the rate of