The specific cause of inflammatory bowel disease (IBD) in animals is frequently unknown; therefore, it is difficult to prescribe a specific treatment for the underlying disorder (see the table Drugs Used for Inflammatory Bowel Disease).
The most common form of IBD is colitis, which is often classified as plasmacytic-lymphocytic, eosinophilic, histiocytic, or granulomatous.
The goal of IBD treatment is to restore normal intestinal motility and to relieve inflammation, spasm, or ulceration. In small animals, dietary therapy is a major component of treatment 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, and 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 due primarily 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 administered to small animals to treat ulcerative or idiopathic colitis or plasmacytic-lymphocytic colitis after dietary causes have been excluded.
Because the salicylate component is only minimally absorbed, its systemic effects are usually minimal. The sulfonamide component may result in keratoconjunctivitis sicca in dogs, and the salicylate component may lead to toxicosis in cats.
Dosage recommendations for sulfasalazine vary widely, and the dosage is gradually decreased 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.
Tylosin is a macrolide antimicrobial used successfully in some dogs with IBD. It is commonly administered on a longterm basis as an alternative to sulfasalazine. The mechanism of action is unknown; however, the activity of tylosin against mycoplasmas, spirochetes, and chlamydiae is suspected to be important. Best results are attained when the powdered form, labeled for use in swine, is mixed with food or added to water. Some dogs may find the bitter taste unpalatable.
Metronidazole has fair efficacy against Giardia, and it has been administered to dogs, cats, and horses with IBD. This efficacy is suspected to be 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 the treatment of metronidazole-induced neurotoxicosis.
The efficacy of glucocorticoids for treating IBD 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. Because they are inexpensive, glucocorticoids are often administered as a first-line treatment in dogs, cats, and horses.
Prednisone is usually administered at immunosuppressive doses, which are slowly tapered to the lowest effective dose every 48 hours. Because of the poor oral bioavailability of prednisone and the poor hepatic metabolism of prednisone to the active compound prednisolone in cats and horses, prednisolone should be administered in these species.
Combination treatment with sulfasalazine, metronidazole, or azathioprine may decrease the overall prednisone dosage needed to achieve the remission of clinical signs.
If adverse effects (severe polyuria or polydipsia, panting, lethargy, etc) of prednisone are substantial, dexamethasonecan be used instead. In some dogs, dexamethasone is much better tolerated, and adverse effects are minimal or nonexistent.
If the adverse effects of prednisone are judged to be severe, it is generally discontinued for 12–36 hours to allow for adequate metabolism and clearance. Prednisone may then be reintroduced at 25%–50% of the previous dose, or alternatively, dexamethasone can be instituted at a low dose.
Budesonide is a glucocorticoid used in humans to treat asthma, rhinitis, and IBD. The human formulation consists of coated granules with a matrix of ethyl cellulose to target release into the lumen of the ileum or ascending colon. Because budesonide undergoes extensive first-pass hepatic metabolism, with 90% of the systemically available drug converted to less active metabolites, theoretically it has increased local activity with minimal systemic effects. A veterinary study found that dogs with IBD did have hypothalamic-pituitary-adrenal axis suppression when administered budesonide.(1) One possible reason for this suppression is that the damaged GI mucosal layer allowed greater systemic drug absorption.
Omega-3 fatty acids have been suggested for treatment in humans with ulcerative colitis or Crohn disease. The addition of omega-3 fatty acids to the diet makes fewer omega-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 IBD. 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 treatment 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 IBD in cats. It is cost-prohibitive in all but very small dogs.
Cyclosporine may also be used in the treatment of steroid-refractory IBD at the labeled doses for treating atopy in dogs and cats. In a study of dogs with IBD, T-cells markedly decreased after treatment with cyclosporine,(2) supporting a mechanism of action by which the expression of interleukin-2 is inhibited, thereby decreasing proinflammatory cytokines.
References
Tumulty JW, Broussard JD, Steiner JM, Peterson ME, Williams DA. Clinical effects of short-term oral budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease. J Am Anim Hosp Assoc. 2004;40(2):120–123. doi:10.5326/0400120
Fellman CL, Archer TM, Stokes JV, Wills RW, Lunsford KV, Mackin AJ. Effects of oral cyclosporine on canine T-cell expression of IL-2 and IFN-gamma across a 12-h dosing interval. J Vet Pharmacol Ther. 2016;39(3):237–244. doi:10.1111/jvp.12280.
