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.
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
T
T
Arakawa
K
K
Higuchi
T
T
Fukuda
H
H
Nakamura
K
K
Kobayashi
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000627:therapeutic use*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000503:physiopathology; D014945:Wound Healing
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D016595:Misoprostol; D064747:Lansoprazole; D015232:Dinoprostone; D009853:Omeprazole