Antidiarrheal Agents

Chapter 34 Antidiarrheal Agents

Pathogenesis of Diarrhea

When clinical signs are acute and there are no systemic signs of illness, symptomatic therapy often takes precedence over achieving a precise diagnosis. When the duration of clinical signs is chronic (>3 weeks), or if there are systemic signs of illness, a determined effort should be made to achieve a specific diagnosis. Diarrhea in companion animals may develop through one or more pathophysiologic mechanisms,1 but one mechanism tends to predominate.1,2

Villous Atrophy

Atrophy of the villous absorptive surface area occurs with many pathologic processes. Atrophy is caused by accelerated loss of enterocytes or decreased production of enterocytes by stem cells in the crypts. Stem cells retain the ability to reconstitute the overlying mucosa, but regeneration may take days to weeks depending upon the pathologic process. Viral infections (e.g., parvovirus, coronavirus, rotavirus) are the most important causes of damage to villus enterocytes in dogs and cats. Viral enteritides are usually acute, self-limiting infections that resolve over a matter of a few days to 1 to 2 weeks. Villous atrophy may result from immune-mediated processes such as gluten-sensitive enteropathy in the Irish Setter dog,3 or as a consequence of food sensitivity reactions in both dogs and cats.4 Food sensitivity reactions are increasingly recognized as an important cause of villous atrophy, malassimilation, and diarrhea in companion animals. Immunosuppressive drugs (e.g., glucocorticoids, vincristine, azathioprine, cyclophosphamide) may also cause severe villous atrophy. Glucocorticoids are frequently prescribed in the management of inflammatory bowel disease (IBD). Antiinflammatory doses of glucocorticoids appear to have minimal effect on epithelial cell turnover, but immunosuppressive doses may abolish epithelial cell renewal. These effects are usually reversible with discontinuation of therapy.

Mucosal Barrier Disruption

Just as the stomach has evolved with mucosal barrier properties to reduce the deleterious effects of gastric acidity, the intestine has evolved with mucosal barrier properties to exclude bacterial pathogens and to maintain oral tolerance.69 Barrier disruption may be caused by moderate to severe inflammation, ulceration, ischemia, cytotoxic drugs, and certain protein-losing states. Inflammatory mediators such as interferon-γ, tumor necrosis factor-α, and platelet-activating factor mediate some of the effects on mucosal barrier disruption.10


The role of dietary hypersensitivity reactions in the pathogenesis of canine and feline chronic diarrhea is incompletely understood, although recent studies suggest that adverse reactions to food antigens are common in dogs and cats with chronic diarrhea.4 True allergy or immunoglobulin E–mediated reactions appear to be rare in companion animals.4 Food hypersensitivity reactions may evoke more generalized inflammatory responses involving histamine, leukotrienes, prostaglandins, substance P, or 5-HT (serotonin) effects on gastrointestinal absorption, secretion, permeability, and motility.

Multiple Pathophysiologic Mechanisms of Diarrhea

Some diarrheal disorders result from one pathogenic mechanism, but others may have several concurrent pathogenic mechanisms, for example, maldigestion, malabsorption, excessive secretion, changes in permeability, protein and lipid exudation, and disordered motility.2 EPI is often regarded as a classic maldigestive disorder. In the absence of pancreatic enzyme secretion, undigested protein, lipid, or carbohydrate cannot be further absorbed. Affected animals develop diarrhea, steatorrhea, and severe protein-calorie malnutrition. These same animals develop SIBO, gastric acid–induced injury to the intestinal mucosa, cobalamin malabsorption, and hypersecretion of fluid and electrolytes. It is for these reasons that pancreatic insufficient animals may have incomplete response with pancreatic enzyme replacement therapy. Bacterial infection is another example of a diarrheal disorder with multiple pathophysiologic mechanisms. The heat-stable enterotoxin of enteropathogenic Escherichia coli stimulates guanylate cyclase production of cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinases, culminating in secretory-type diarrhea. At the same time, platelet-activating factor, prostaglandins, and leukotrienes produced during bacterial infection may contribute to the malabsorption and disordered motility of E. coli infections.

Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Antidiarrheal Agents

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