I. Introduction to Peptic Ulcer Disease (PUD)

Peptic Ulcer Disease (PUD) is a condition characterized by breaks in the gastrointestinal mucosa that extend through the muscularis mucosa. These lesions typically occur in areas exposed to acid and pepsin, most commonly the stomach (gastric ulcers) and the duodenum (duodenal ulcers).

Goals of Antiulcer Therapy

• Alleviate symptoms (e.g., pain, dyspepsia).
• Promote ulcer healing.
• Prevent complications (e.g., bleeding, perforation, obstruction).
• Prevent recurrence.
• Eradicate H. pylori infection if present.

II. H2 Receptor Antagonists (H2RAs)

H2RAs are among the earliest and most effective classes of drugs used to reduce gastric acid secretion. They selectively block histamine H2 receptors on the parietal cells, thereby decreasing acid production stimulated by histamine, gastrin, and acetylcholine.

Key Drugs & Characteristics

III. Proton Pump Inhibitors (PPIs)

PPIs are the most potent suppressors of gastric acid secretion. They irreversibly bind to and inhibit the H+/K+-ATPase enzyme (the proton pump) in the secretory canaliculi of parietal cells, effectively blocking the final common pathway of acid secretion, regardless of the stimulus.

Mechanism of Action

Due to irreversible binding, acid secretion only resumes when new proton pumps are synthesized, typically taking 24-48 hours. This results in a long duration of action despite a short plasma half-life.

Key Drugs & Clinical Considerations

Long-term Side Effects (Controversial/Emerging Evidence)

• Increased risk of fractures (hip, wrist, spine) due to reduced calcium absorption.
• Increased risk of Clostridium difficile infection due to altered gut flora.
• Hypomagnesemia (especially with diuretics).
• Vitamin B12 deficiency (due to reduced intrinsic factor release).
• Possible increased risk of renal disease and dementia (requires more research).
• Potential for rebound acid hypersecretion upon discontinuation.

IV. Antacids

Antacids are weak bases that neutralize existing gastric acid, providing rapid but short-lived relief of heartburn and dyspepsia. They do not prevent acid production but buffer it.

Common Antacid Agents

V. Prostaglandin Analogs

Prostaglandins, especially PGE1 and PGE2, play a crucial role in maintaining mucosal integrity by inhibiting acid secretion, stimulating mucus and bicarbonate secretion, and increasing mucosal blood flow. Misoprostol is a synthetic PGE1 analog.

Misoprostol

• Mechanism: Binds to prostaglandin receptors on parietal cells, inhibiting histamine-stimulated acid secretion. Also enhances mucosal defense mechanisms (mucus, bicarbonate, blood flow).
• Primary Use: Prevention of NSAID-induced gastric ulcers, especially in high-risk patients (elderly, history of ulcers).
• Side Effects: Diarrhea, abdominal cramping, nausea.
• Crucial Contraindication: Pregnancy. It is a potent uterine stimulant and can cause abortion.

VI. Mucosal Protective Agents

These agents work by forming a protective barrier over the ulcer crater or by stimulating local defense mechanisms.

A. Sucralfate

• Mechanism: A complex of sulfated sucrose and aluminum hydroxide. In an acidic environment (pH < 4), it polymerizes and forms a viscous, sticky gel that selectively binds to positively charged proteins at the base of ulcers and erosions, creating a physical barrier against acid, pepsin, and bile.
• Use: Duodenal ulcers, stress ulcer prophylaxis.
• Administration: Must be taken on an empty stomach at least 1 hour before meals and at bedtime. Requires acid for activation, so avoid concurrent use with antacids, H2RAs, or PPIs (administer 30 mins apart).
• Side Effects: Constipation (due to aluminum), minimal systemic absorption.

B. Colloidal Bismuth Subcitrate (CBS) / Bismuth Subsalicylate (BSS, Pepto-Bismol)

• Mechanism: Bismuth compounds have several actions:
  • Form a protective coating over ulcers.
  • Directly stimulate prostaglandin, mucus, and bicarbonate secretion.
  • Have direct antimicrobial activity against H. pylori.
  • Adsorb pepsin.
• Use: Part of H. pylori eradication regimens, traveler's diarrhea.
• Side Effects: Blackening of stool and tongue (harmless), rarely bismuth encephalopathy with high doses.

VII. Helicobacter pylori Eradication Therapy

H. pylori is a spiral-shaped bacterium that colonizes the gastric mucosa and is a major cause of PUD, gastric lymphoma (MALToma), and gastric cancer. Eradication of H. pylori is essential for preventing ulcer recurrence.

Treatment Regimens

Treatment typically involves a combination of antibiotics and a PPI for 10-14 days to maximize efficacy and minimize resistance.

VIII. Other Considerations & Lifestyle Management

While pharmacology is central, lifestyle adjustments play a supportive role in managing PUD and GERD.

• Diet: Avoid trigger foods (spicy, acidic, fatty foods, chocolate, caffeine, mint).
• Smoking & Alcohol: Both can impair healing and provoke symptoms; cessation is highly recommended.
• Stress Reduction: Stress does not cause ulcers but can exacerbate symptoms.
• NSAID Use: Minimize or avoid NSAIDs if possible. If necessary, use at the lowest effective dose, with food, or consider a COX-2 selective inhibitor or co-therapy with a PPI/Misoprostol.
• Elevate Head of Bed: For nocturnal GERD symptoms.
• Weight Management: Obesity can worsen GERD.