GI Drugs Pt 3

Learning Objectives

  • Understand drugs used to treat ulcers, their mechanisms, and potential side effects.

  • Recognize drugs used to modulate rumen motility and their clinical applications.

Antacids and Antiulcer Drugs

  • Causes of Ulcers:

    • Hyperacidity: Excessive secretion of gastric acid leads to tissue erosion.

    • Bile reflux: Bile entering the stomach can contribute to ulceration.

    • Toxin accumulation: Substances can damage the gastric mucosa.

    • Post-surgical stress: Stresses from surgery can alter gastric secretions.

    • Inhibition of prostaglandin formation: Important for mucosal protection.

    • In ruminants, carbohydrate overload can alter rumen pH and microflora, resulting in rumen acidosis, exacerbating ulcer formation.

Oxyntic (Parietal) Cells

  • Stimulation of HCl production occurs via:

    • Histamine (acting on H2 receptors) mediating acid secretion.

    • Gastrin (via Gastrin receptors) released in response to gastric distention.

    • Acetylcholine (through ACh receptors) released from the vagus nerve stimulating gastric function.

  • These parietal cells are crucial for maximum acid production in the stomach, enabling digestion and absorption of nutrients.

Gastrin and Acetylcholine Release

  • Gastrin:

    • Released in response to stomach distention and the presence of peptides, stimulating more acid secretion and promoting gastric motility.

  • Acetylcholine:

    • Released from the parasympathetic nervous system, it enhances gastric motility and secretion, increasing digestive efficiency.

  • Histamine:

    • Release can be stimulated by mast cell tumors, which can lead to excessive gastric acid production.

Veterinary Antacid/Antiulcer Drugs

  • NSAIDs and Corticosteroids can promote ulcer formation due to their inhibitory effect on protective mucosal mechanisms, increasing vulnerability to damage.

  • Importance of Aspirin:

    • Its lipophilicity in the stomach heightens the risk of ulceration, necessitating caution in administration.

Antacids

  • Function:

    • Reverse, prevent, and control damage to the gastrointestinal (GI) tract, maintaining mucosal integrity.

  • Classification:

    • Systemic antacids: Act systemically to lower acid production.

    • Non-systemic antacids: Neutralize acid locally in the stomach.

  • Non-systemic antacids include:

    • Calcium (e.g., Tums®) – may cause constipation due to calcium's binding properties.

    • Magnesium (e.g., Milk of Magnesia®) – can induce diarrhea, a result of its osmotic effect.

    • Aluminum (e.g., Amphojel®) – also linked to constipation; often used in combination therapies to mitigate side effects.

    • Combination products (e.g., Maalox®, Mylanta®) help to balance these side effects and enhance overall efficacy.

Non-systemic Antacids (Continued)

  • Effects:

    • Changes in drug forms due to pH modification can affect the absorption of concurrent medications in the intestine.

    • Timing is crucial when administering other medications with non-systemic antacids to avoid interactions.

    • Chelation concerns: Tetracyclines should not be administered concurrently with calcium-based antacids, as this can impede antibiotic absorption and effectiveness.

Systemic Antacids

  • Work to decrease stomach acid production through inhibition of acid secretion pathways.

  • Examples:

    • Cimetidine (Tagamet®) - H2 receptor antagonist, reduces acid secretion.

    • Ranitidine (Zantac®) - similar mechanism, previously common for managing ulcer treatment.

    • Famotidine (Pepcid®) - more potent with fewer side effects.

    • Nizatidine (Axid®) - has effects similar to famotidine but varies in pharmacokinetics.

  • Available in both injectable and oral forms for versatile therapeutic applications.

Systemic Antacid Interference

  • Caution is advised when using systemic antacids with cardiac medications, as they may interfere with metabolic pathways, necessitating dose adjustments of concurrent medications to prevent adverse effects.

Proton Pump Inhibitors

  • Omeprazole:

    • Available as Prilosec OTC®, Gastrogard®, Ulcergard®.

    • It is more effective than H2 antagonists, as it works by irreversibly inhibiting the proton pump in parietal cells, leading to significant reduction in stomach acid production.

Sucralfate (Carafate®)

  • Acts as a "gastric band-aid" by physically coating the ulcer area, providing a protective barrier against gastric acid and enzymes.

  • Needs an acidic environment to dissolve and work correctly; best absorbed when taken on an empty stomach.

  • Can be mixed with water for easy administration, enhancing patient compliance.

Misoprostol (Cytotec®)

  • A synthetic PgE-1 analog, providing cytoprotective effects by increasing mucus and bicarbonate production in the gastric lining.

  • Displaying mixed results as a preventative measure; primarily used for treating GI ulcers.

  • Side effects may include potential constipation and abdominal discomfort; contraindicated in pregnancy due to uterine stimulation potential.

Ruminatorics

  • Definition: Drugs that stimulate rumen motility, enhancing digestive functions in ruminants.

  • Neostigmine (Stiglyn®):

    • Inhibits acetylcholinesterase, prolonging acetylcholine activity, positively impacting rumen contractions.

    • Used for diagnosis and treatment of myasthenia gravis in dogs, reflecting its importance in neuromuscular function and digestive health.

Bloat (Ruminal Tympany)

  • Result of gas accumulation in the rumen, whereby the normal gas expulsion mechanisms are disrupted.

  • Types:

    • Free gas bloat: accumulation of gas due to physical obstruction or decreased motility.

    • Frothy bloat: foam formation making gas expulsion more difficult, often due to high legume intake.

  • Treatment options include DSS, mineral oil, or poloxalene; these help reduce surface tension in frothy bloat.

  • Administer via oral stomach tube or direct ruminal injection for rapid results.

  • Ionophores such as Monensin (Rumensin) can act as preventative measures by altering rumen fermentation patterns.

Other Drugs Used for GI Problems

  • Antimicrobials not usually essential but can be beneficial in specific cases, particularly in preventing or treating secondary infections.

  • Oral Electrolyte Replacements, Pancreatic Enzyme Supplements, and Corticosteroids may also be indicated based on specific clinical conditions and presentations.

Antimicrobials

  • Sulfasalazine (Azulfidine®):

    • Used for its anti-inflammatory effects, particularly effective in the colon for conditions like Inflammatory Bowel Disease (IBD) and colitis.

    • Caution with sulfonamides is advised due to the potential risk of keratoconjunctivitis sicca.

Antimicrobials (Continued)

  • Tylosin (Tylan®):

    • Effective against both gram-positive and gram-negative bacteria; anti-infective properties.

    • Caution: Do not use in horses due to severe adverse reactions.

  • Metronidazole (Flagyl®):

    • Effective against protozoan infections, notably Giardia.

    • Monitor for CNS side effects with prolonged usage, making regular evaluations necessary for long-term treatment.

Oral Electrolyte Replacement

  • Used during episodes of stress or dehydration, particularly in young animals or during disease states.

  • Supplements like Bounce Back are designed for various species to restore balance and hydration.

Pancreatic Enzyme Supplements

  • Treat exocrine pancreatic insufficiency in dogs and cats, a condition leading to maldigestion and malabsorption of nutrients.

  • Must be mixed with food prior to feeding to maximize their effectiveness, ensuring adequate absorption in the small intestine.

Corticosteroids

  • Typically not the first choice for GI problems due to potential side effects and complications, including ulceration.

  • Their controversial use is indicated for specific conditions like severe inflammation but must be approached cautiously to minimize risks associated with long-term administration.