Drugs Used in Treatment of Chronic Colitis (Monogastric)
The specific cause of chronic colitis in animals is frequently unknown; therefore, it is difficult to prescribe a specific treatment for the underlying disorder (see Drugs Used for Chronic Colitis). Colitis is often classified as plasmacytic/lymphocytic, eosinophilic, histiocytic, or granulomatous. The goal of colitis therapy is to restore normal intestinal motility and to relieve inflammation, spasm, or ulceration. In small animals, dietary therapy is a major component of therapy for chronic colitis (see Colitis in Small Animals).
Drugs Used for Chronic Colitis
Sulfasalazine is composed of sulfapyridine and 5-aminosalicylic acid (mesalamine) joined by an azo bond. The bond is broken by bacteria in the colon to release the two drugs. The sulfonamide component is absorbed into the circulation, whereas the salicylic acid component is active locally in the GI tract. Less than half of the salicylate component is absorbed systemically. Clinical efficacy appears to be primarily due to the anti-inflammatory effect of the salicylate component. There is evidence for antilipoxygenase activity, decreased interleukin-1, decreased prostaglandin synthesis, and oxygen radical scavenging activity. Sulfasalazine is commonly used in small animals in the therapy of ulcerative or idiopathic colitis or of plasmacytic-lymphocytic colitis once dietary causes have been excluded.
Because the salicylate component is only minimally absorbed, its systemic effects are minimal. The sulfonamide component may cause keratoconjunctivitis sicca in dogs, and the salicylate component may cause toxicity in cats. Dosage recommendations for sulfasalazine vary widely, and the dosage is gradually reduced after an initial response. New products have been developed to overcome the difficulty of the 5-aminosalicylic acid reaching the colon and the systemic adverse effects. Mesalamine is a pH-sensitive, coated 5-aminosalicylic acid. The polymer coating prevents release of the active drug until it reaches the colon. Olsalazine consists of two molecules of 5-aminosalicylic acid joined together by an azo bond. Mesalamine is also available as an enema. Rectal administration allows delivery of active drug to the colon. It appears useful in dogs with chemotherapy-induced hemorrhagic colitis or with idiopathic distal proctitis. It may also be useful in dogs with perianal fistulas.
Tylosin is a macrolide antimicrobial used successfully in some animals with colitis. It is commonly administered on a chronic basis as an alternative to sulfasalazine therapy. The mechanism of action is unknown, but it is suspected that its activity against mycoplasmas, spirochetes, and chlamydiae is important. Best results are attained when the powdered form, labeled for use in swine, is mixed with food or added to water. Some animals may find the bitter taste unpalatable.
Metronidazole has fair efficacy against Giardia, and it is also efficacious in some cases of diarrhea in which giardiasis was not definitively diagnosed. It is suspected that this efficacy is related to the activity of metronidazole against anaerobic bacteria. Metronidazole also has an immunosuppressive effect on the GI mucosa by decreasing the cell-mediated response. Adverse neurologic effects have been reported in dogs and cats treated with metronidazole. Diazepam appears effective for treatment of neurotoxicity.
The efficacy of glucocorticoids for treating colitis is probably related to their anti-inflammatory and immunosuppressive capabilities. Some cases of colitis may be due to autoantibodies and T lymphocytes directed against colonic epithelial cells. Glucocorticoids suppress the immune reaction and are used when biopsy results suggest eosinophilic or plasmacytic-lymphocytic colitis. They are used in dogs, cats, and horses, often when all other forms of therapy have failed. Immunosuppressive doses of oral prednisone or dexamethasone are usually administered and slowly tapered to every-other-day therapy with the lowest effective dose.
Budesonide is a glucocorticoid used in people to treat asthma, rhinitis, and inflammatory bowel disease. Budesonide has a high affinity for glucocorticoid receptors, high hepatic clearance, and high local and low systemic activity compared with prednisone or dexamethasone. The human formulation of budesonide consists of coated granules with a matrix of ethyl cellulose to target release into the lumen of the ileum or ascending colon. It is not known whether the human budesonide formulation provides release in the same anatomic site in dogs, but it appears clinically effective in some dogs.
N-3 fatty acids have been suggested for therapy in people with ulcerative colitis or Crohn disease. The addition of n-3 fatty acids to the diet makes fewer n-6 fatty acids available for the arachidonic acid cascade. Several formulations are available for small animals, and raw linseed oil may be added to horses’ grain for this effect.
Potent immunosuppressive drugs such as azathioprine are used to manage some forms of colitis. Azathioprine is metabolized to 6-mercaptopurine, which is immunosuppressive by interfering with nucleic acid synthesis and by impairing lymphocyte proliferation. It may take several weeks or months of therapy for azathioprine to become maximally effective. Cats particularly should be monitored for adverse effects, including myelosuppression, hepatic disease, and acute pancreatic necrosis. Chlorambucil has been used in place of azathioprine in some difficult or refractory cases of feline inflammatory bowel disease. It is too expensive to use in all but very small dogs.