Role of NSAIDs in Peptic Ulcer Disease (PUD) - ANSWER Topical (Local) Effects:
- NSAID is weak organic acid
- enters gastric epithelial cell
- ionized and trapped in cell —> cell damage
Systemic Effects:
- ↓ mucosal prostaglandin synthesis
- Possibly also: ↑ adherence of neutrophils to vascular endothelium → free radicals and proteases which
damage mucosa
,Role of H. Pylori in PUD - ANSWER Gram negative bacillus colonizes stomach and duodenum
50% of population worldwide infected with H. Pylori - most never get PUD
Evidence that H. Pylori Causes PUD - ANSWER • 75% of patients with PUD have H. Pylori
infection
• Duodenal ulcers more common among people with H. Pylori
infection than those without infection
• Treating the infection helps ulcer healing
• Ulcers recur less frequently if H. Pylori is eradicated
Mechanism of Ulcer Promotion - ANSWER • Secretes enzymes which disrupt protective mucus
layer
• Presence of bacteria causes neutrophils and other inflammatory cells to gather at site → injury to local
cells
• Produces urease → carbon dioxide and ammonia → toxic to
gastric mucosa
H. Pylori and the Promotion of Gastric Cancer - ANSWER • The bacterium is a carcinogen
• Association with mucosa-associated lymphoid tissue (MALT) lymphomas
• If patient has MALT lymphoma, treatment of H. Pylori usually causes tumor regression
Antibacterial Rx for Patients with Gastric/Duodenal Ulcer and H. Pylori - ANSWER Necessary to
treat H. pylori with antibacterials
- must use at least 2 antibacterial to avoid contributing to resistance
• Clarithromycin
• Amoxicillin
• Bismuth
• Tetracycline
• Metronidazole
• Tinidazole
H. Pylori Treatment - Common Regimens - ANSWER Regimens may contain: bismuth,
clarithromycin, or levofloxacin
, Quadruple Bismuth Therapy:
• Bismuth plus metronidazole plus tetracycline plus PPI for 14 days
• Eradication rate 91%
Triple Clarithromycin Therapy:
• Clarithromycin plus amoxicillin plus PPI bid for 14 days (metronidazole if pcn allergy)
• Lots of Clarithromycin resistance = eradication rate 70-80%
Concomitant Therapy:
• Clarithromycin plus amoxicillin plus nitroimidazole (tinidazole or metronidazole) plus PPI for 14 days
• Needed if high rates of resistance
Other H. Pylori Treatment Regimens - High Resistance - ANSWER Hybrid Therapy:
• Amoxicillin plus PPI for 7 days. Then, amoxicillin plus clarithromycin plus nitroimidazole, plus PPI for 7
days
• Better eradication rates, but very complicated for patients
Levofloxacin-Based Therapies:
• Triple therapy: Levofloxacin plus amoxicillin plus PPI for 10 to 14 days (90% eradication)
• Quadruple therapy: Levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) higher eradication
rates as compared with clarithromycin triple therapy for 10 days (95% eradication)
Choosing Antibiotic Regimen - H. Pylori - ANSWER • Risk factors for macrolide resistance
• Presence of penicillin allergy
• Risk factors for macrolide resistance:
- Prior exposure to macrolide therapy for any reason
- High local clarithromycin resistance rates ≥15 percent or eradication rates with clarithromycin triple
therapy ≤85 percent
If one or more risk factors for macrolide resistance: avoid clarithromycin-based therapy
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