Acid-Peptic Disease Therapeutics

Proton Pump Inhibitors - Proton Pump Pummelers

• MOA: Irreversibly block $H^+/K^+$ ATPase (proton pump) in active parietal cells, making them the most potent acid suppressants. Prodrugs, require acidic environment for activation.
• Examples: Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole. (📌 Suffix: "-prazole")
• Kinetics: Administer 30-60 min before first meal for maximal effect.
• Uses: GERD, peptic ulcers, Zollinger-Ellison syndrome, H. pylori eradication regimens, NSAID-induced ulcer prophylaxis.
• Adverse Effects (Long-term):
  • Nutrient deficiencies: ↓ Vit B12, ↓ Ca²⁺ (↑ fracture risk), ↓ Mg²⁺.
  • Infections: ↑ risk of C. difficile, pneumonia.
  • Kidney: Acute interstitial nephritis (AIN), CKD.
  • Rebound hyperacidity upon discontinuation.
• Interactions: Omeprazole/Esomeprazole (CYP2C19 inhibitors) ↓ clopidogrel efficacy ⚠️. Pantoprazole/Rabeprazole are safer alternatives.

⭐ PPIs: Prodrugs activated in acidic parietal cell canaliculi, ensuring targeted inhibition of the proton pump.

H2 Receptor Antagonists - Histamine Hijackers

• MOA: Reversibly block H2 receptors on parietal cells → ↓ cAMP → ↓ H+/K+ ATPase activity → ↓ gastric acid secretion (basal & stimulated).
• Drugs ("-tidine"): Cimetidine, Ranitidine, Famotidine, Nizatidine.
• Uses: Peptic Ulcer Disease (PUD), Gastroesophageal Reflux Disease (GERD) (mild), Zollinger-Ellison syndrome (adjunct), stress ulcer prophylaxis.
• Adverse Effects:
  • Generally well-tolerated. CNS effects (confusion, dizziness, especially in elderly or with renal/hepatic impairment).
  • Cimetidine:
    • Antiandrogenic effects (gynecomastia, impotence, galactorrhea).
    • CYP450 enzyme inhibitor (↑ levels of warfarin, phenytoin, theophylline). 📌 CIMETIDINE = Cytochrome Inhibitor Man.
  • Tolerance (tachyphylaxis) can develop with prolonged use.
• Kinetics: Predominantly renal excretion (dose adjustment in renal failure).

⭐ Cimetidine is notorious for causing gynecomastia due to its antiandrogenic properties and for inhibiting multiple CYP450 enzymes, leading to significant drug-drug interactions (e.g., with warfarin, phenytoin).

Antacids & Mucosal Protectants - Soothe & Shield Guardians

• Antacids: Neutralize gastric acid. Rapid, short relief.

  • Mechanism: Weak bases + HCl → salt + $H_2O$.
  • Types:
    • $Mg(OH)_2$: Rapid; SE: Diarrhea. 📌 Mg=Must go.
    • $Al(OH)_3$: Slower; SE: Constipation, ↓phosphate. 📌 AluMINIMUM poo.
    • $CaCO_3$: Potent; SE: Constipation, rebound, milk-alkali syndrome.
    • $NaHCO_3$: Systemic; SE: Alkalosis, fluid retention.
  • Interactions: Chelation (tetracyclines, iron), altered pH affects drug absorption.

• Mucosal Protectants: Shield mucosa, enhance defense.

  • Sucralfate:
    • Forms viscous polymer at pH <4; binds ulcer base. Stimulates PGs.
    • Give on empty stomach; avoid antacids/H2RA/PPIs. SE: Constipation.
  • Colloidal Bismuth Compounds (Bismuth Subsalicylate):
    • Coats ulcers, antimicrobial (H. pylori), ↑mucus/bicarb/PGs.
    • SE: Black tongue/stools.

    ⭐ Bismuth subsalicylate: salicylate content poses Reye's syndrome risk in children with viral illness.

2, Al(OH)3, CaCO3, NaHCO3 highlighting onset, duration, side effects, and systemic absorption)

H. pylori Eradication - Bug Busters Hit Squad

• Goal: Ulcer healing, ↓ recurrence. Multi-drug regimens essential.

• Duration: Typically 10-14 days.

• Confirmation: 4 weeks post-therapy (Urea Breath Test, Stool Antigen).

• Triple Therapy (OAC/CAP): 📌 "CAP": Clarithromycin, Amoxicillin, PPI.

  • PPI (e.g., Omeprazole 20mg BD)
  • Clarithromycin 500mg BD
  • Amoxicillin 1g BD (or Metronidazole 400mg BD if penicillin-allergic)

• Quadruple Therapy (PBMT): 📌 "Please Make Tummy Better": PPI, Bismuth, Metronidazole, Tetracycline.

  • PPI BD
  • Bismuth subcitrate QID
  • Metronidazole 400mg TDS
  • Tetracycline 500mg QID

⭐ Bismuth-containing quadruple therapy is recommended first-line in areas with high clarithromycin resistance (>15%) or for patients with previous macrolide exposure.

High‑Yield Points - ⚡ Biggest Takeaways

• PPIs are most potent acid suppressors; irreversibly inhibit H+/K+ ATPase.
• H2 blockers (e.g., Famotidine) cause reversible competitive inhibition of H2 receptors.
• Misoprostol (PGE1 analog) for NSAID-induced ulcers; contraindicated in pregnancy.
• Sucralfate requires acidic pH for a protective ulcer coating.
• Antacids offer rapid neutralization; Mg²⁺ causes diarrhea, Al³⁺ causes constipation.
• Bismuth compounds aid H. pylori eradication and protect mucosa.
• Long-term PPIs: risk of fractures, hypomagnesemia, C. difficile infection_._