UMLS:C0038358 - FACTA Search

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Query: UMLS:C0038358 (gastric ulcer)
5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastric H+,K+ ATPase--the gastric acid pump--is the molecular target for the class of antisecretory drugs called the proton-pump inhibitors (PPIs). These compounds--omeprazole, lansoprazole, and pantoprazole--contain, as their core structure, 2-pyridyl methylsulfinyl benzimidazole. The H+,K+ ATPase is a heterodimer composed of a 1034-amino acid catalytic alpha peptide and a glycosylated 291-amino acid beta subunit. The alpha subunit probably contains 10 membrane-spanning sequences; the beta, a single transmembrane segment. The PPIs have a pKa of about 4.0; hence they accumulate only in the acidic secretory canaliculus of the stimulated parietal cell. Here they undergo conversion to a cationic sulfenamide, which then reacts with available cysteines on the extracytoplasmic face of the alpha subunit. Omeprazole reacts and forms disulfide bonds with cys813(822) and cys892; lansoprazole, with cys813(822), cys892, and cys321; and pantoprazole, with cys813 and -822. The antisecretory effect of the drugs reflects their short plasma half-life (approximately 60 min), the number of active pumps during that time, and the recovery of pumps following biosynthesis and reversal of inhibition. These drugs also show synergism with either amoxicillin or clari- thromycin in eradicating Helicobacter pylori, an organism shown to be important in duodenal and gastric ulcer disease. Their action is probably due to elevation of pH in the environment of the organism, rather than to any direct action.
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PMID:The pharmacology of the gastric acid pump: the H+,K+ ATPase. 759 95

Omeprazole plus amoxicillin cures Helicobacter pylori infection. The hypothesis was tested that low acidity is a predictor of outcome. Fifty patients with relapsing or complicated, or both H pylori positive duodenal (n = 25) or gastric ulcer (n = 25) were randomly treated with either omeprazole 20 mg twice daily plus amoxicillin 1 g twice daily or with omeprazole 40 mg twice daily plus amoxicillin 1 g twice daily over two weeks. After one week of combined treatment, a 24 hour gastric pH measurement was performed in all patients. H pylori cure rate was 67%. Patients who later turned out to be cured had higher pH values during night time and after meals (p < 0.05). In an explorative analysis drug compliance, smoking, location of the ulcer (duodenum versus stomach), age, and grade of body gastritis were additional predictors of the outcome. Smoking (p = 0.006), compliance (p = 0.037), duodenal ulcer disease (p = 0.065), and young age (p = 0.021) were related to high acidity. In conclusion, the success of eradication treatment with omeprazole and amoxicillin in ulcer patients infected with H pylori depends on intragastric pH. Drug compliance, smoking habits, location of ulcer, age, and activity of body gastritis are other predictors and in part related to intragastric acidity.
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PMID:Intragastric acidity as a predictor of the success of Helicobacter pylori eradication: a study in peptic ulcer patients with omeprazole and amoxicillin. 767 77

The relationship between the inhibition of intragastric acidity and healing has been determined for both duodenal and gastric ulcers, with a stronger correlation being evident in duodenal ulcer. Omeprazole is clearly more effective than H2-receptor antagonists in healing duodenal ulcers and in the resolution of attendant symptoms. As the recommended treatment periods are shorter with omeprazole (e.g. 2-4 weeks) than with H2-receptor antagonists (4-8 weeks), omeprazole has also been shown to be more cost-effective. Long-term management strategies for peptic ulcer are evolving rapidly in the light of evidence that Helicobacter pylori eradication reduces or eliminates ulcer relapse. Regimens, such as omeprazole in combination with amoxycillin or clarithromycin, that both eradicate H. pylori and heal ulcers rapidly are appealing because they are simple, well tolerated, convenient and efficient in both healing ulcers and preventing relapse. This comprehensive approach appears to be evolving as the dominant strategy for the future treatment of peptic ulcer diseases. Gastric ulcer disease is also treated more effectively with omeprazole than with H2-receptor antagonists, both in terms of speed and reliability of healing, and in terms of symptom resolution. At 4 weeks, symptom resolution has been specifically examined in six comparative trials; in three of these, omeprazole was superior to the H2-receptor antagonist, and in the other three was at least as good as the H2-receptor antagonist. Omeprazole, 40 mg once daily, effectively heals non-steroidal anti-inflammatory drug (NSAID)-induced ulcers in about 90% of cases, even if NSAID therapy is continued, and is probably the treatment of choice for patients with ulcers requiring continued NSAID therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Emerging strategies for managing peptic ulcer disease. 804 24

Omeprazole is an inhibitor of gastric H+,K(+)-ATPase. Although the major proton transport of osteoclast is mediated by a vacuolar-type H(+)-ATPase which is different from the gastric H+,K(+)-ATPase, in vitro studies have demonstrated that omeprazole inhibits bone resorption. In this study, the effect of omeprazole on bone resorption was evaluated in patients who had a history of gastric ulcer and were treated with maintenance doses of H2 blocker without any gastric complaints at the study time. H2-blocker administration was changed to omeprazole treatment in the study group and to no treatment in the control group. Urinary excretion of hydroxyproline and calcium decreased after omeprazole treatment in the study group. Serum intact PTH, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase (TRAP) increased in this group. In the control group, there were not any changes in these parameters. The discrepancy between serum TRAP and urinary excretion of hydroxyproline and calcium in the study group was thought to be due to the suppression of bone resorption by omeprazole, which probably interfered the acidification at resorption lacunae and resulted in the inactivation of TRAP and other lysosomal enzymes. The results of our study suggest the possibility that the specific inhibitors of the osteoclastic proton pump (such as bafilomycins) will more effectively suppress bone resorption and be useful for the treatment of metabolic bone diseases with increased bone resorption.
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PMID:Effect of omeprazole, an inhibitor of H+,K(+)-ATPase, on bone resorption in humans. 810 18

Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once-daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once- or twice-daily dosing in patients with Zollinger-Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger-Ellison syndrome. Side effects are infrequent when the drug is used for the short-term management of ulcers.
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PMID:Omeprazole: a comprehensive review. 843 67

Gastric ulcer is relatively infrequent, and clinical trails are often based on small-sized samples. The aim of this study was to define the "gold standard" therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977-1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraith's radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03-3.52), 3.94 (2.28-6.80), 1.76 (1.08-2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H2 blockers [OR (CI 95%) at four weeks: 1.16 (0.91-1.47), 1.11 (0.80-1.55), respectively]. H2 blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37-1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37-1.20)]. Omeprazole is more effective than H2 blockers [OR (CI 95%) at four weeks: 2.00 (1.57-2.55)]. It is concluded that H2 blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H2 blockers do not have significant advantages over the older types; omeprazole can be regarded as the "gold standard" for active gastric ulcer treatment.
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PMID:Short-term treatment of gastric ulcer. A meta-analytical evaluation of blind trials. 865 42

A total of 1,456 patients were available for the All Patients Treated analysis of two large, randomized, double-blind, multicenter, controlled studies (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment [ASTRONAUT] and Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management [OMNIUM]). These studies examined the efficacies of omeprazole, 20 and 40 mg once daily (both studies), ranitidine, 150 mg twice daily (ASTRONAUT), and misoprostol, 200 microg four times daily (OMNIUM), for the healing of gastric ulcer, duodenal ulcer, or erosions, and the relief of dyspeptic symptoms. At entry, patients were receiving, and continued to receive, nonsteroidal anti-inflammatory drugs (NSAIDs), and had a gastric or duodenal ulcer, and/or >10 erosions in the stomach or duodenum at initial endoscopy. Patients were randomized to blinded treatment for 4/8 weeks until treatment success, which was defined as the healing of ulcer(s), <5 erosions at any site, and not more than mild dyspeptic symptoms. The proportions of patients reaching treatment success by 8 weeks were 77% with both doses of omeprazole, 63% with ranitidine, and 71% with misoprostol. In patients who initially had a gastric ulcer, more ulcers were healed at 8 weeks with omeprazole, 20 (83%) and 40 mg once daily (82%), than with ranitidine (64%) or misoprostol (74%). In patients who initially had a duodenal ulcer, 93% were healed at 8 weeks with omeprazole, 20 mg once daily, compared with 88% for omeprazole, 40 mg once daily, 79% for ranitidine, and 79% for misoprostol. Erosions healed slightly faster at 4 weeks with misoprostol, compared with the other regimens, but by 8 weeks most patients had <5 erosions per gastroduodenal region in each treatment group. Diarrhea and abdominal pain were more common in patients taking misoprostol, as were adverse events leading to withdrawal. Patients with duodenal ulcer or erosions at entry and the presence of Helicobacter pylori were good prognostic factors for overall treatment success. Using a model that included only patients with ulcers, those with smaller ulcers also had a higher likelihood of achieving treatment success. Against the background of these new data, omeprazole is the treatment of choice for healing NSAID-associated ulcers, on the basis of its efficacy and tolerability, and the optimal dose appears to be 20 mg once daily.
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PMID:New data on healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee. 957 22

Four large clinical studies have shown that omeprazole, 20 mg once daily, is effective in preventing the significant gastroduodenal consequences of nonsteroidal anti-inflammatory drugs (NSAIDs). In the Scandinavian Collaborative Ulcer Recurrence (SCUR) study, patients were randomized (without initial endoscopy) to receive omeprazole or placebo for up to 3 months. Of the patients treated with omeprazole, 24.7% experienced treatment failure, compared with 50.0% of those on placebo. Fewer patients in the omeprazole group than in the placebo group developed a peptic ulcer (4.7% versus 16.7%, respectively) or dyspeptic symptoms (8.2% versus 20.0%, respectively). In the Omeprazole versus Placebo as Prophylaxis of Ulcers and Erosions from NSAID Treatment (OPPULENT) study, patients were also randomized to receive omeprazole or placebo. The estimated probability of remaining in remission for 6 months while receiving omeprazole was 0.78, compared with 0.53 for placebo. Fourteen (16.5%) patients on placebo developed peptic ulcer(s), compared with three (3.6%) patients on omeprazole. The Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) study consisted of a healing and a prophylactic phase. Patients who successfully completed the healing phase were re-randomized to receive omeprazole, misoprostol, or placebo for up to 6 months. In patients receiving omeprazole, 36.5% experienced treatment failure, compared with 48.6% of those on misoprostol, and 67.7% of those on placebo. Omeprazole and misoprostol appeared to be equally effective in preventing gastric ulcer; by contrast, omeprazole was highly effective in preventing duodenal ulcer, when compared with misoprostol and placebo. The Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment (ASTRONAUT) study also consisted of a healing and a prophylactic phase. Patients who successfully completed the healing phase were re-randomized to receive omeprazole or ranitidine for up to 6 months. In patients receiving omeprazole, 26.2% experienced treatment failure, compared with 37.7% of those on ranitidine. The percentages of patients with a peptic ulcer relapse were 5.7% for omeprazole and 19.5% for ranitidine. The data show that omeprazole is an effective and well-tolerated agent for both primary and secondary (maintenance) prophylaxis in patients receiving NSAIDs.
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PMID:Progress in prophylaxis against nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee. 957 24

Proton pump inhibitors (PPIs) are drugs which irreversibly inhibit proton pump (H+/K+ ATPase) function and are the most potent gastric acid-suppressing agents in clinical use. There is now a substantial body of evidence showing improved efficacy of PPIs over the histamine H2 receptor antagonists and other drugs in acid-related disorders. Omeprazole 20 mg/day, lansoprazole 30 mg/day, pantoprazole 40 mg/day or rabeprazole 20 mg/day for 2 to 4 weeks are more effective than standard doses of H2-receptor antagonists in healing duodenal and gastric ulcers. Patients with gastric ulcers should receive standard doses of PPIs as for duodenal ulcers but for a longer time period (4 to 8 weeks). There is no conclusive evidence to support the use of a particular PPI over another for either duodenal or gastric ulcer healing. For Helicobacter pylori-positive duodenal ulceration, a combination of a PPI and 2 antibacterials will eradicate H. pylori in over 90% of cases and significantly reduce ulcer recurrence. Patients with H. pylori-positive gastric ulcers should be managed similarly. PPIs also have efficacy advantages over ranitidine and misoprostol and are better tolerated than misoprostol in patients taking nonsteroidal anti-inflammatory drugs (NSAIDs). In endoscopically proven gastro-oesophageal reflux disease, standard daily doses of the PPIs are more effective than H2-receptor antagonists for healing, and patients should receive a 4 to 8 week course of treatment. For severe reflux, with ulceration and/or stricture formation, a higher dose regimen (omeprazole 40 mg, lansoprazole 60 mg, pantoprazole 80 mg or rabeprazole 40 mg daily) appears to yield better healing rates. There is little evidence that PPIs lead to resolution of Barrett's oesophagus or a reduction of subsequent adenocarcinoma development, but PPIs are indicated in healing of any associated ulceration. In Zollinger-Ellison syndrome, PPIs have become the treatment of choice for the management of gastric acid hypersecretion.
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PMID:Proton pump inhibitors. Pharmacology and rationale for use in gastrointestinal disorders. 977 9

Gastric ulceration has been found to occur in 80-90% of Thoroughbreds in active race training. Previously, variable success has been reported using mucosal surface protectants and H2 receptor antagonist. Omeprazole, a substituted benzimidazole, has been shown to inhibit gastric acid secretion in both man and animals. Fourteen horses, in active race training and with endoscopic evidence of moderated to severe gastric ulceration were divided into 2 groups: Group 1 (7 horses) were given placebo paste orally once daily for 28 days; Group 2 (7 horses) received 1.54 g active omeprazole in the placebo once daily for 28 days. Logs detailing administration and acceptability of the paste, and the horse's feeding and training regime were maintained by the trainer of each horse. Endoscopic examination of the stomach occurred at the beginning of the trial, and at 13-17 days and 27-31 days following commencement of the trial. Those horses that were free of ulceration on Days 27-31 were reexamined on Days 35-49. Acceptability of the paste, whether with or without active omeprazole, was deemed excellent in all horses except on one occasion, when one horse swallowed the paste following initial mild reluctance. Of the horses given the placebo (Group 1), 3 were withdrawn after the 13-17 day endoscopic examination: 1 horse to be given a H2 receptor antagonist, 1 horse was removed from training due to aryepiglottic entrapment and 1 horse had a greater than 10% fall in bodyweight from the start of the trial. Of the horses given active omeprazole (Group 2), one horses was relocated to another race track following the 13-17 day endoscopic examination. For the horses given placebo (Group 1), there was no change in the severity of ulceration. In contrast, the severity of ulceration in the horses given active omeprazole was significantly reduced at 13-17 days and 27-31 days. In 2 Group 2 horses, ulcers that had been completely eliminated subsequently returned when reexamined at 35-49 days. The results of this study suggest that omeprazole, employing a once daily dosing schedule, is effective at reducing the severity or eliminating gastric ulcers in Thoroughbreds in active race training.
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PMID:Acceptability of a paste formulation and efficacy of high dose omeprazole in healing gastric ulcers in horses maintained in race training. 1069 85

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