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Mechanistic Deep Dive
H. pylori Pathogenesis
- Survives in gastric acid (urease produces NH3)
- Adheres via BabA, SabA
- Damages mucosa
- VacA, CagA virulence factors
- Triggers chronic inflammation â ulcer or atrophy + cancer
NSAID Mechanism
- COX-1 inhibition â â prostaglandins â â mucosal protection
- COX-2 selective less ulcerogenic
- Higher doses + longer duration â more ulcerogenic
Vonoprazan Mechanism
- Potassium-competitive acid blocker (PCAB)
- Faster onset + more sustained acid suppression
- Effective when PPI fails
- Especially helpful for severe acid suppression needs
Recent Trials & Updates
Vonoprazan FDA 2022
- For H. pylori
- Higher eradication rates
- Less affected by CYP2C19 polymorphisms
Levofloxacin Resistance
- Increasing globally
- Use for rescue when standard fails
Pylera (Combined Bismuth-Based)
- Convenient quadruple therapy
CYP2C19 Polymorphisms + PPI
- Poor metabolizers have higher PPI levels
- Extensive metabolizers may have reduced efficacy
- Asian populations: higher poor metabolizer prevalence
High-Yield Specialist Points
PPI Side Effects (Long-Term)
- B12 deficiency
- Hypomagnesemia
- C. diff (3-4x risk)
- Pneumonia (mild â)
- Hip fracture (controversial)
- Gastric polyps
- Iron deficiency
H2 Receptor Antagonists
- Famotidine preferred (ranitidine recalled)
- Less potent than PPI
- Tachyphylaxis chronic use
Antacids
- Calcium, magnesium, aluminum
- Quick relief, short duration
Sucralfate
- Mucosal protectant
- Limited use now (interferes with absorption)
Misoprostol
- PG analog
- For NSAID-induced; less used (diarrhea, abortifacient)
Bismuth Subsalicylate Side Effects
- Black stool, black tongue
- Salicylate concerns
- Rare encephalopathy
Antibiotic Resistance Patterns
- Clarithromycin: 20-30%+ globally
- Metronidazole: 30-40%+
- Levofloxacin: 20%+
- Amoxicillin + tetracycline: < 5%
Penicillin Allergy Alternatives
- Quadruple therapy (no amoxicillin needed)
- Levofloxacin-based
Pediatric PUD
- Less H. pylori (mostly idiopathic or stress)
- Adolescent rates similar to adult
- Diagnosis + treatment similar
Pregnancy + H. pylori
- Generally defer treatment
- If needed: amoxicillin + clarithromycin (not first-trimester)
- Quadruple usually avoided
Stress Ulcer Prophylaxis (ICU)
- For mechanical ventilation > 48 h, coagulopathy
- PPI or H2 RA
- Stop when no longer needed
Gastric Cancer + H. pylori
- Major risk factor
- H. pylori eradication reduces risk
- Gastric atrophy + intestinal metaplasia surveillance
MALT Lymphoma + H. pylori
- Eradication of H. pylori â 70-80% regression
- Gastric MALT lymphoma low-grade
- Surveillance EGD
Vonoprazan Drug Interactions
- Less CYP2C19 dependence
- Different metabolism
Pearls
- PUD: H. pylori most common; NSAID in developed
- DU pain relieved by food; GU worsened; biopsy GU
- Quadruple therapy preferred (rising clarithromycin resistance)
- Vonoprazan-based new option (FDA 2022)
- Functional dyspepsia: PPI + H. pylori + TCA
- ZES: gastrin > 1000 + MEN1 + multiple atypical ulcers
- PPI long-term side effects: B12, Mg, C. diff, fractures (concerns)