Gastrointestinal Protectants

Chapter 181 Gastrointestinal Protectants



Michael D. Willard, DVM, MS, DACVIM



KEY POINTS



• Histamine-2 receptor antagonists (H2RAs) are competitive inhibitors of gastric acid secretion, meaning that they lower gastric acid secretion but do not abolish it. However, they also diminish pepsin secretion.

• Ranitidine and nizatidine are H2RAs that are also gastric prokinetic agents.

• Cimetidine inhibits hepatic P-450 cytochrome enzyme activity so much that it can be used therapeutically (e.g., to minimize acetaminophen toxicity) or can delay metabolism of drugs.

• Proton pump inhibitors (PPIs) are noncompetitive inhibitors of gastric acid secretion, meaning that they can inhibit gastric acid secretion to a greater extent than H2RAs. However, it can take 2 to 5 days for them to achieve maximal effectiveness when given orally.

• Sucralfate is an unabsorbed drug that binds to ulcerated or eroded mucosa. It can adsorb other drugs, delaying or inhibiting their absorption.

• Misoprostol is a prostaglandin analog that was designed to prevent ulceration and erosion due to nonsteroidal antiinflammatory drugs (NSAIDs). However, it is not as effective or reliable in preventing NSAID-induced ulceration in dogs as it is in humans.

• Orally administered antacids that are used to neutralize gastric acid have a shorter duration of action and rarely are used to manage or prevent ulcers and erosions in veterinary medicine.


INTRODUCTION


Gastrointestinal ulceration and erosion (GUE) is an important problem in dogs, but much less common in cats. Stress (defined here as anything causing substantial hypoperfusion or anoxia of the gastric mucosa) and drug therapy (especially nonsteroidal antiinflammatory drugs [NSAIDs] but also dexamethasone) are especially common causes of GUE in dogs. Prednisolone at dosages commonly administered is rarely ulcerogenic unless there is concurrent gastric hypoxia or hypoperfusion, severe spinal disease, or concurrent use of NSAIDs. Stress ulceration may be due to hypotensive shock, systemic inflammatory response syndrome, severe life-threatening illness, and extreme exertion. Hyperacidity (usually caused by gastrinoma or mast cell tumor) may cause GUE, but more commonly causes duodenal as opposed to gastric lesions. Hepatic failure, renal failure tumors, and, to a much lesser extent, foreign bodies may also cause GUE.


Gastrointestinal (GI) protectants are primarily indicated to heal existing gastric ulcers and erosions. Removing the cause of the ulceration or erosion markedly enhances efficacy, as does maintaining GI perfusion. Protectants are often poorly effective at preventing ulceration when the cause (e.g., use of NSAIDs, continued poor perfusion or anoxia to the gastric mucosa) persists. However, when there is a known cause of ulceration or erosion that cannot be readily alleviated, these drugs are often given in the hope that they will at least retard, if not prevent, ulceration. See Table 181-1 for a list of commonly used GI protectants and dosages.



Table 181-1 Selected Gastric Protectants That Are Used in Dogs and Cats

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Proton pump inhibitors (PPIs) and H2RAs prevent ulceration caused by certain forms of stress (i.e., probably a combination of poor gastric mucosal blood flow, hypoxia, and possibly other factors) in dogs.1 None of the drugs discussed in this chapter has shown clear efficacy in preventing ulceration due to steroids (e.g., dexamethasone, methylprednisolone sodium succinate),2–4 and although helpful against NSAIDs-induced GUE, they typically are not completely effective.5–9 There is no evidence that combination therapy (e.g., using H2RAs plus sucralfate) is any more effective than using just one drug.


Drugs decreasing gastric acid secretion or otherwise used for managing gastric ulceration and erosion are not antiemetics in the strict sense (i.e., they have no effect on the medullary vomiting center or the chemoreceptor trigger zone); however, they can have an antidyspeptic effect that lessens nausea. Therefore they may be used to stimulate appetite or to enhance the efficacy of true antiemetics. When used to manage existing ulcers or erosions, one generally expects to see some evidence of improvement (i.e., less nausea, less bleeding) within 2 to 5 days of beginning therapy, assuming that the initiating cause has been eliminated. If there is no evidence of improvement in that time, endoscopic evalaution and/or surgical removal should be considered.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Gastrointestinal Protectants

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