General concepts of the treatment of gastric ulcers

Gastric anatomy and ulcer location - horses

1. Equine squamous gastric disease (ESGD)

2. Equine glandular gastric disease (EGGD)

3. Gastroduodenal ulcer disease (GDUD)

Successful treatment of ulcers involves one or more of the following strategies:

Reduce gastric acid secretion, Neutralize gastric acid, Protect the gastric mucosa

Enhance mucosal defense and repair, Remove or reduce precipitating factors

Eradicate Helicobacter pylori when relevant, Treat complications, Prevent recurrence

Balance between aggression and defense

Reducing acid secretion is one of the most important therapeutic approaches

Major drugs include:

Proton-pump inhibitors, H₂-receptor antagonists

Antimuscarinic drugs in selected circumstances

2: Neutralize Existing Gastric Acid

Antacids act directly on acid already present in the stomach.

Ex: Magnesium hydroxide, Aluminium hydroxide, Calcium carbonate, Sodium bicarbonate

Limitations of antacids

have a short duration of action; gastric emptying removes them from the stomach.

They are more useful for rapid symptomatic relief than as sole therapy for ulcer

3: Protect the Gastric Mucosa

Some drugs do not primarily reduce acid secretion; instead, they create or enhance a protective barrier over damaged mucosa

Ex: Sucralfate → particularly important because it acts locally at the site of mucosal injury

4: Enhance Mucosal Defense

Prostaglandins are important physiological mediators of gastric mucosal protection.

Drugs that mimic prostaglandin activity can protect the stomach

Major drug: Misoprostol - important in the prevention and treatment of NSAID associated gastric injury

5: Remove the Underlying Cause

Pharmacological treatment alone may fail if the precipitating factor continues.

Potential causes include: NSAID administration, Glucocorticoid use, H. pylori infection, Severe systemic disease, Stress, Renal disease, Hepatic disease, Neoplasia, FB, Diet, Hypergastrinemia

6: Treat Helicobacter pylori

Treatment involves acid suppression and Antimicrobial therapy, using a combination of antibiotics

Eliminate the organism, Promote ulcer healing, Reduce recurrence

Anti-ulcer drugs - H2 receptor antagonist

Cimetidine, ranitidine, famotidine

Recommended H2 receptor antagonist

Dogs: ranitidine and famotidine

Horses: cimetidine and ranitidine

Calves: cimetidine and ranitidine

Adverse effects of H2 antagonists

good safety record

Cimetidine inhibits the clearance of other drugs via its action as a CYP450 inhibitor.

Increased gastric pH can affect the oral absorption of those drugs that require an acidic pH for drug dissolution

Cimetidine additional effects

strengthens the gastric mucosal defenses and enhances cytoprotection.

Ranitidine additional effects

stimulates motility and increases gastric emptying and colonic motility via an anticholinesterase(AChE) action

Anti-ulcer drugs - proton pump inhibitors

Omeprazole, pantoprazole, esomeprazole

Indications of proton pump inhibitors for Dogs and cats

omeprazole, esomeprazole, and others

For the treatment of cancer or NSAID-induced ulcers

Indications of proton pump inhibitors for horses

omeprazole

For the treatment of stress or NSAID-induced ulcerations

PPIs adverse effects

Elevated gastrin concentrations lead to a trophic effect on the gastric mucosa. Rebound hypersecretion of acid in cats after chronic administration.

The second effect is often small intestinal bacterial overgrowth (SIBO).

PPIs inhibit CYP450 enzymes

Anti-ulcer drugs – Gastric protectant

Sucralfate

Sucralfate uses

Beneficial for the treatment of gastric ulcers in animals, but there is no evidence that it is effective for the prevention of gastritis or gastric ulcers

Useful in the prevention of esophagitis in cats

Sucralfate adverse effects

Reduction of the absorption of other drugs (tetracyclines)

Constipation

Anti-ulcer drugs - Prostaglandin analogs

Misoprostol

Misoprostol uses

PGE analogue

helps to prevent GI ulcers but is less beneficial for treating ulcers once they occur.

Its use appears to be limited to NSAID therapy

Misoprostol adverse effects

may cause abdominal discomfort, cramping, diarrhea, and abortion.

There have been anecdotal benefits for treating or preventing right dorsal colitis in horses associated with phenylbutazone treatment

Misoprostol - not for use in pregnant animals

Increasing uterine contractions

Possible expulsion of uterine contents in pregnant animals, so this drug is not recommended in pregnant animals

Anti-ulcer drugs - Antacids

Bismuth subsalicylate, aluminum hydroxide, magnesium hydroxide

Aluminum hydroxide uses

treatment of gastric ulceration, esophagitis, or gastritis

Bismuth uses

cytoprotective and has anti-endotoxic and weak antibacterial properties

Antacid adverse effects

rare and include interference with the oral absorption of other drugs due to magnesium's chelating effects and reduced stomach acid