H2-receptor antagonist-refractory ulcer: its pathophysiology and treatment.

We assessed the intraluminal pH and mucosal prostaglandin E2 (PGE2) concentrations in patients (nonresponders) whose gastric ulcer did not heal after an initial 2 months and subsequent 3 months of treatment with one of five H2-receptor antagonists (H2RAs). The efficacy of misoprostol, a PGE1 analogue, or AG-1749, a proton-pump inhibitor, on ulcer healing in nonresponders was also tested. The percentage of time (24-h measurement) during which the pH was 3 or more was higher in the basal condition (no H2RA) in nonresponders than in good responders with healing in the first 2 months. H2RAs increased this percentage satisfactorily in nonresponders as well as in good responders. The mean mucosal PGE2 concentration in the ulcer rim was 26 ng/g of tissue in nonresponders, much lower than in good responders. Treatment with misoprostol combined with an H2RA resulted in 60% success for ulcer healing within the next 2 months in nonresponders, without affecting the intraluminal pH measured during treatment with an H2RA alone. AG-1749 raised the percentage of time with high pH to 99% from the 68% obtained with an H2RA and cured 88% of this type of ulcer. These results suggest that extremely low PGE2 levels in gastric mucosa are related to the effectiveness of the H2RA. In such a condition, the small amount of gastric acid that is still secreted even during treatment with an H2RA may interrupt ulcer healing. Therefore, treatment with a prostaglandin analogue combined with an H2RA or treatment with a proton-pump inhibitor may be useful for ulcer healing in nonresponders.
AuthorsT Arakawa, K Higuchi, T Fukuda, H Nakamura, K Kobayashi
JournalJournal of clinical gastroenterology (J Clin Gastroenterol) Vol. 13 Suppl 1 Pg. S129-33 ( 1991) ISSN: 0192-0790 [Print] UNITED STATES
PMID1682356 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)
Chemical References
  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Misoprostol
  • Lansoprazole
  • Dinoprostone
  • Omeprazole
  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents (therapeutic use)
  • Dinoprostone (metabolism)
  • Female
  • Gastric Mucosa (metabolism)
  • Histamine H2 Antagonists (therapeutic use)
  • Humans
  • Hydrogen-Ion Concentration
  • Lansoprazole
  • Male
  • Middle Aged
  • Misoprostol (therapeutic use)
  • Omeprazole (analogs & derivatives, therapeutic use)
  • Peptic Ulcer (drug therapy, physiopathology)
  • Wound Healing

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