Acid-Peptic Disease Therapeutics

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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. Parietal cell and acid secretion regulation

⭐ 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). Gastric parietal cell acid secretion regulation
  • 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_._

Practice Questions: Acid-Peptic Disease Therapeutics

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Flashcards: Acid-Peptic Disease Therapeutics

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Gastric bezoars are commonly associated with antacids such as _____.

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Gastric bezoars are commonly associated with antacids such as _____.

sucralfate

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