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GI Pharmacology & Disease Management — Study Guide

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⚠️ Pharmacokinetic vs. Pharmacodynamic Drug Interactions (Key Principle)

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🔴 PEPTIC ULCER DISEASE (PUD) — Priority Topic

Etiology

• H. pylori infection (most common cause)
• NSAIDs/ASA (second most common)
• Rare: Zollinger-Ellison syndrome (gastrinoma), stress ulcers

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Goals of Treatment

1. Eradicate H. pylori (if present)
2. Heal the ulcer (acid suppression)
3. Prevent recurrence
4. Avoid complications (bleeding, perforation, obstruction)

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🧪 H. pylori Testing (Before & After Therapy)

• Before: Urea breath test, stool antigen test, endoscopy + biopsy (CLO test/histology)
• After (confirm eradication): Urea breath test or stool antigen test — at least 4 weeks after completing therapy

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💊 H. pylori Eradication Regimens

1. Standard Triple Therapy (Classic — now declining due to resistance)

⚠️ Problem: Clarithromycin resistance is now >15–20% in many regions, significantly reducing eradication rates. This regimen is no longer the preferred first-line in many guidelines.

• PPI + Clarithromycin + Metronidazole (instead of amoxicillin)

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2. Bismuth Quadruple Therapy (BQT) — Current Preferred First-Line (ACG 2024)

✅ This is now the preferred empiric regimen when antibiotic susceptibility is unknown (ACG Clinical Practice Guideline, p. 1). Bismuth works by: (1) topical bactericidal effect on H. pylori, (2) protective coating on mucosa, (3) prevention of bacterial adhesion.

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3. Concomitant Therapy (Non-Bismuth Quadruple)

All four drugs given simultaneously. Overcomes clarithromycin resistance by adding metronidazole.

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4. Sequential Therapy

• Days 1–5: PPI + Amoxicillin
• Days 6–10: PPI + Clarithromycin + Metronidazole (or tinidazole)

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5. Hybrid Therapy

• Days 1–7: PPI + Amoxicillin
• Days 8–14: PPI + Amoxicillin + Clarithromycin + Metronidazole

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6. Rifabutin Triple Therapy (Salvage / Alternative)

Suitable empiric alternative when BQT cannot be used, or in treatment-naive patients without penicillin allergy (ACG, p. 1). Also used in second-line after BQT failure.

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7. Potassium-Competitive Acid Blocker (PCAB) Dual Therapy

• Vonoprazan (PCAB) + Amoxicillin

Newer option; vonoprazan provides stronger, more sustained acid suppression than PPIs (not pH-dependent activation).

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🔄 How to Replace/Switch When First-Line Fails

Key principle: Never re-use an antibiotic class the patient has already been treated with (risk of pre-existing resistance).

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Acid Suppression Drugs Summary

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NSAID-Induced Ulcers

• If NSAID must be continued: add PPI (co-prescription)
• Prophylaxis: Misoprostol or PPI
• H. pylori test-and-treat if taking NSAIDs

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🟡 DYSPLASIA in the GI Tract

Key Contexts:

Management of Dysplasia:

• Low-grade dysplasia (LGD): Surveillance colonoscopy, continued mucosal control (control of UC/Crohn inflammation reduces dysplasia risk — ACG UC Guidelines, p. 7, Key Concept #14)
• High-grade dysplasia (HGD): Typically colectomy (UC) or endoscopic resection if localized
• H. pylori eradication may regress early gastric lesions before dysplasia develops

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🟠 ULCERATIVE COLITIS (UC)

Key Features

• Affects mucosa only (superficial), continuous from rectum proximally
• Bloody diarrhea, urgency, tenesmus

Disease Extent (ACG UC Guidelines, p. 7):

1. Proctitis — within 18 cm of anal verge
2. Left-sided colitis — sigmoid to splenic flexure
3. Extensive colitis/pancolitis — beyond splenic flexure

Treatment by Severity

Biologics in UC:

5-ASA Drugs (Aminosalicylates):

• Mesalamine (oral, enema, suppository)
• Sulfasalazine = sulfapyridine + 5-ASA (PK note: sulfapyridine carrier can cause side effects)
• Mechanism: ↓ mucosal inflammation via inhibition of prostaglandins and NF-κB

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🔵 CROHN'S DISEASE

Key Features vs. UC

Treatment

Budesonide — important PK point: extensive first-pass metabolism → acts locally in ileum/right colon with minimal systemic side effects (vs. prednisone)

Antibiotics in Crohn's:

• Metronidazole + Ciprofloxacin — used for perianal disease, fistulas, bacterial overgrowth
• Not used for luminal disease induction

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📊 Quick Comparison: IBD vs. PUD

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🔑 Key Drug Interactions to Remember

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Summary: Peptic Ulcer Treatment Algorithm

H. pylori positive?
    ↓ YES
Antibiotic susceptibility known?
    → NO → Bismuth Quadruple Therapy × 14 days (first choice)
           OR Rifabutin triple therapy (if no penicillin allergy)
    → YES → Susceptibility-guided therapy

Treatment failed?
    → Switch antibiotic class; never repeat same antibiotics
    → Optimized BQT → then Rifabutin triple
    → Last resort: culture-guided / susceptibility-based

H. pylori negative?
    → NSAID-induced? → Stop NSAID + PPI × 4–8 weeks
    → Idiopathic? → PPI maintenance therapy

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