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Compendium June 2002 Drug Therapy/GI Disease 463 Table 8. Immune-Modulating Drugs Drug Dose Comment Metronidazole Dogs and cats: cholangitis—7.5 mg/kg Neurotoxicity at high doses or with liver PO q12–24h; bacterial overgrowth—10–15 mg/kg PO q12–24h; stomatitis—15 mg/kg PO q12–24h; Giardia, IBD—10–30 mg/kg PO q12–24h function impairment Prednisone Dogs and cats: 1–2 mg/kg PO q12h; Can cause polyuria/polydipsia, polyphagia, cats with eosinophilic enteritis: 2–3 mg/kg PO q12h gastric ulcers, Cushing’s syndrome Azathioprine Dogs: 50 mg/m2 (1–1.5 mg/kg) PO q24h for Can cause bone marrow suppression; CBC 2 wk, then every other day for maintenance; monitoring required; lag period of weeks cats: 0.3–0.5 mg/kg PO q48h for full effect Cyclophosphamide Dogs: 50 mg/m2 PO four times per wk; cats: half Can cause bone marrow suppression; CBC of a 25-mg tablet PO four times per wk monitoring required; can cause vomiting/ diarrhea and hemorrhagic cystitis (dogs) Chlorambucil Dogs: 0.1–0.2 mg/kg PO q48h; cats: 0.25–0.5 mg/kg PO q48–72h Can cause bone marrow suppression Tylosin Dogs and cats: 11–200 or 20–40 mg/kg PO q12h; Broad dose range with wide safety margin; 1 /4–1 tsp with food q8–12h; 5–10 mg/kg PO each gram contains 100 mg tylosin; sprinkle q8–12h on food Sulfasalazine Dogs: 10–30 mg/kg PO q8h; cats: 20 mg/kg Can cause keratoconjunctivitis sicca; use or 250 mg PO q8h (three times), then q24h with caution in cats because of possible salicylate toxicity Mesalamine Dogs: 10–20 mg/kg PO q6–8h May decrease tear production in dogs Olsalazine Dogs and cats: 10–20 mg/kg PO q12–24h Not reported to decrease tear production in dogs at the 5-HT 4 receptor and is reported to stimulate colonic activity in dogs and cats and stimulate gastric emptying in dogs. 28 Other new benzamide prokinetic drugs such as mosapride citrate, cinitapride, clebopride, and renzapride are currently being developed and may become available in the United States in the future. 4 Misoprostol Misoprostol may be used in dogs and cats with refractory constipation by initiating giant migrating complex pattern and increasing colonic propulsive activity as reported in dogs. 29 ANTIMICROBIALS Use of antimicrobials to treat nonspecific gastroenteritis can cause more harm than good by negatively influencing the normal GI microflora. Misuse of antibiotics in animals with gastroenteritis can lead to disruption of the normal bacterial flora. This can cause increased bacterial colonization of the bowel and overgrowth of antibiotic-resistant pathogenic strains of bacteria (e.g., Clostridium perfringens, Clostridium difficile), which in turn can result in severe and chronic inflammation of the bowel. 30 Helicobacter pylori colonization occurs with high prevalence in the gastric mucosa of healthy as well as sick dogs and cats. 31 Infection causing clinical illness is not proven and is being investigated; indications for treatment are also being investigated. 32 Proper use of antimicrobials for specific GI diseases includes adjunct treatment for secondary bacterial overgrowth caused by exocrine pancreatic insufficiency or inflammatory bowel disease (IBD; Table 7). Other indications for use are primary bacterial overgrowth of the proximal small intestinal bowel and diarrhea induced by Salmonella, Campylobacter, Clostridium, or enterotoxigenic E. coli, with evidence of these organisms on fecal culture, fecal cytology, or fecal enterotoxin assay. Bacterial adherence to villi on histopathologic examination of intestinal biopsies is another indication for antimicrobial treatment. Patients with bloody vomitus or bloody diarrhea or that have severe mucosal injury and mucosal barrier breakdown should also be placed on antimicrobial therapy. This includes patients with parvovirus, hemorrhagic gastroenteritis, salmon poisoning disease, and postchemotherapy complications. Translocation of normal bacterial flora from the intestinal lumen and into the bloodstream can lead to septicemia and death, particularly in immunosup-
464 Small Animal/Exotics Compendium June 2002 pressed patients. Choosing the proper antibiotic therapy should be based on the known sensitivity of the antibiotic to the normal bacterial flora of the GI tract or the specific bacterial pathogen, if known. Stomach microflora has a transient population of clostridia, streptococci, lactobacilli, E. coli, and spirochetes. 33 The proximal small intestinal bowel has low numbers of gram-positive bacteria, including streptococci and lactobacilli. Anaerobes and gram-negative bacteria are the predominate organisms in the distal small intestinal bowel and colon, with over 90% of anaerobic bacteria (i.e., Bacteroides, clostridia, lactobacilli) comprising the colonic environment. 33 Other considerations when choosing an antibiotic include using a bactericidal drug for severe hemorrhagic diarrhea or for immunosuppressed patients; using drugs that can be given by parenteral route in patients that are vomiting, septic, or unconscious; choosing an antibiotic based on culture and sensitivity results when available; and being aware of toxic side effects (e.g., nephrotoxicity of an aminoglycoside in dehydrated animals). IMMUNE-MODULATING DRUGS Inflammatory or immune-mediated diseases of the bowel are treated by immunosuppressive therapy. In dogs and cats, IBD is the most commonly diagnosed disease by endoscopic biopsy or surgical biopsy of the GI tract. Treatment is directed at reducing the inflammation and implementing a controlled diet (Table 8). 34–36 Drugs that can effectively help decrease the inflammatory response in the GI tract are metronidazole, salicylates, prednisone, azathioprine, cyclophosphamide, chlorambucil, and potentially cyclosporine. 36 Tylosin, a macrolide-like antibiotic used for bacterial overgrowth, has also been reported to be effective in some patients with IBD, although the exact mechanism of action is unknown. 36 It is available in a powder and can be sprinkled on the animal’s food. Metronidazole Metronidazole is an antibiotic with sensitivity to anaerobic bacteria, although it does not cause detrimental alteration of normal bacterial flora. It also has immunemodulating properties that suppress cell-mediated responses, is an antiprotozoal, and has positive effects on brush-border enzyme levels and the uptake of nutrients by the intestine (e.g., glucose, amino acids). 37 It is unknown which of its actions is responsible for its efficacy in treating IBD. Metronidazole can be effective in mild cases of IBD and provide good control. In moderate to severe cases, it can be used as a combination therapy with lower doses of prednisone. Salicylates Sulfasalazine, a salicylate, is used specifically for inflammation of the colon and is the treatment of choice for chronic colitis. This drug contains sulfapyridine and 5-aminosalicylate joined by an azo bond that is separated in the colon. The 5-aminosalicylate component, which acts as a local suppressor of inflammation, is an NSAID that inhibits cyclooxygenase and lipoxygenase activity inhibiting prostaglandin and leukotriene synthesis. In mild to moderate cases of colonic IBD, this drug can be beneficial when used alone. In more severe cases, this drug should be used in combination with metronidazole or prednisone. Side effects include anorexia, vomiting, diarrhea, and keratoconjunctivitis sicca (which can lead to corneal ulceration); in cats, anemia has been reported. Preparations of 5-aminosalicylate without the sulfapyridine component (mesalamine, olsalazine) may prevent keratoconjunctivitis sicca and are commonly used in human medicine for long-term treatment. 38 However, mesalamine may decrease tear production in dogs.
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