Gastric Inhibitors Notes

Aims

• Describe mechanisms of action of drugs affecting gastric acid, including:
  • Antacids
  • Secretion inhibitors
  • Mucosal protectants
  • Antibiotics
• Discuss uses of drugs and conditions they treat

The Problem

• Gastric secretion and its components:
  • Bicarbonate (HCO3-)
  • Mucus
  • Blood flow
  • Growth factors
  • Cell renewal
  • Prostaglandins
  • Harmful factors affecting gastric health:
  • H+ ions, pepsins
  • Ethanol
  • NSAIDs
  • Bile acids
  • Ischemia
  • Smoking
  • Helicobacter pylori
  • Stress, hypergravity
• Gastric juice secreted: ~2.5L per day
  • Functions:
  • Kills microorganisms
  • Assists digestion
  • Facilitates absorption of iron, calcium, and vitamin B12.

Conditions Resulting from Acid Issues

• Backflow of acid and stomach contents into the esophagus:
  • Heartburn/acid reflux
  • Gastro-oesophageal reflux disease (GORD)
  • Zollinger-Ellison syndrome
  • Peptic ulcers
• Related anatomy: Healthy liver and pancreas, tumors on pancreas.

The Solution: Therapeutic Options

• For peptic ulcer/reflux therapy:
  • Antacids
  • Secretion inhibitors:
  • H2 antagonists
  • Proton pump inhibitors (PPIs)
  • Mucosal protectants
  • Antibiotics

Antacids

• Mechanism:
  • Direct acid neutralization.
• Benefits:
  • Symptomatic relief
  • Can heal duodenal ulcers but less effective for gastric ulcers.

Chemical Reactions of Antacids:

1. Aluminum Hydroxide
   $Al(OH)<em>3(s) + 3 HCl(aq) ightarrow AlCl</em>3(aq) + 3 H_2O(l)$

   • Gradual action; can cause constipation.

2. Calcium Carbonate
   $CaCO<em>3(s) + 2 HCl(aq) ightarrow CaCl</em>2(aq) + H<em>2O(l) + CO</em>2(g)$

   • Short-term relief; potential for hypercalcemia.

3. Magnesium Carbonate
   $MgCO<em>3(s) + 2 HCl(aq) ightarrow MgCl</em>2(aq) + H<em>2O(l) + CO</em>2(g)$

   • Insoluble; can cause diarrhea.

4. Magnesium Hydroxide
   $Mg(OH)<em>2(s) + 2 HCl(aq) ightarrow MgCl</em>2(aq) + 2 H_2O(l)$

5. Sodium Bicarbonate
   $NaHCO<em>3(aq) + HCl(aq) ightarrow NaCl(aq) + H</em>2O(l) + CO_2(g)$

   • Can cause belching; risk of Na+ overload.

Secretion Inhibitors

H2 Antagonists

• Mechanism: Competitive inhibitors of H2 receptors.
• Effects: Decrease both basal and food-stimulated acid secretion by >90%.
• Main compounds:
  • Cimetidine (Tagamet®)
  • Ranitidine (Zantac®)
  • Nizatidine (Axid®)
  • Famotidine (Pepcid®)
• Side effects: Diarrhea, dizziness, muscle pain.

Proton Pump Inhibitors (PPIs)

• Mechanism: Potent, selective, and irreversible inhibition of $H^+ K^+ ATPase$.
• Effects: Reduce both basal and stimulated acid secretion.
• Characteristics:
  • Prodrugs activated by low pH; accumulate in cannaliculi of parietal cell.
  • Main compounds:
  • Omeprazole
  • Esomeprazole
  • Lansoprazole
  • Pantoprazole
  • Half-life: ~1 hour but effects last ~3 days.
• Side effects: Uncommon.

Mucosal Protectants

Alginates

• Mechanism: Increase viscosity and adherence of mucus to esophageal mucosa.
• Action: React with stomach acid to form gel-like substance, creating a raft that blocks reflux.

Sucralfate

• Composition: Complex of aluminum hydroxide and sulphated sucrose.
• Action:
  • Releases aluminum in the presence of acid.
  • Forms complexes with mucus, decreasing degradation by pepsin; limits diffusion of H+ ions.

Arachidonic Acid & NSAIDs

• Negative effects on gastric protection.
• Misoprostol: analogue of prostaglandin E1, provides protective effects.

Antibiotics for H. pylori

• Background: 50% of world population infected; 80% asymptomatic.
• Implications: Gastric ulcers, duodenal ulcers, gastric cancer.
  • Carriers: 10-20% lifetime risk of gastric ulcer, 1-2% stomach cancer.
• Testing methods:
  • Blood antibody test
  • Stool test
  • Breath test
  • Endoscopic biopsy
• Treatment: Triple therapy management with:
  • Clarithromycin
  • Amoxicillin
  • Omeprazole (replace amoxicillin with metronidazole if allergic to penicillin).
  • For clarithromycin-resistant strains, use levofloxacin.
  • Add bismuth chelate for quadruple therapy to prevent bacillus adherence to mucosa.

Risks Associated with Gastric Inhibitors

• Increased risk of infections e.g., Clostridium difficile.
• Reduced absorption of:
  • Iron
  • Magnesium
  • Vitamin B12
• Increased risk of fractures.
• Other potential side effects include:
  • Gastric neuroendocrine tumor
  • Dementia
  • Kidney disease
  • Myocardial infarction
  • Pneumonia
  • Osteoporosis
  • Dysbiosis
  • Small bowel injury
  • Micronutrient deficiency
  • Fundic gland polyps.

Knowledge Check Questions

• Why might H2 antagonists lead to anemia, while PPIs do not?
• Why might gastric inhibitors affect the pharmacological effects of other drugs, such as digitalis?