Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying degrees of gastroduodenal mucosal damage. These agents are most frequently used for the treatment of rheumatic diseases because they are highly effective in reducing joint pain and swelling. Histamine H2-receptor antagonists, omeprazole, sucralfate, and misoprostol are drugs available for the treatment of gastric mucosal damage caused by NSAIDs. In controlled clinical studies, all these drugs effectively heal gastric and duodenal injury if NSAIDs are discontinued. However, current data suggest that if NSAIDs are continued while gastrointestinal damage is present, only misoprostol and omeprazole have demonstrated efficacy in healing gastric mucosal injury. Misoprostol also effectively heals NSAID-induced duodenal injury. At this time, no data exist on the efficacy of other antiulcer drugs in healing duodenal erosions or ulceration if NSAID administration is continued. Regarding prevention of NSAID-induced gastric ulcer, controlled clinical studies with H2 antagonists and sucralfate have failed to show any therapeutic benefit. Ranitidine, however, has shown efficacy in preventing NSAID-induced duodenal ulcers. The coadministration of misoprostol with NSAIDs to patients who have either osteoarthritis or rheumatoid arthritis prevents the development of gastric and duodenal ulcers. Based on current published information, this property distinguishes misoprostol from other antiulcer drugs.
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PMID:Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs. 139 9

One hundred sixty-two patients chronically ingesting ibuprofen, piroxicam, or naproxen for osteoarthritis, who had abdominal pain and an endoscopically proven gastric ulcer were evaluated for eight weeks in a randomized, double-blind trial comparing misoprostol (200 micrograms four times daily with meals and at bedtime) (N = 77) with placebo (N = 85). Patients discontinued their usual daily dose of antiarthritic medication throughout the study period, and an endoscopy was performed at four weeks and eight weeks (if necessary) to assess ulcer healing. Gastric ulcers were defined as circumscribed breaks in the gastric mucosa of 0.3 cm in diameter or greater. Misoprostol therapy significantly accelerated the rate of gastric ulcer healing compared to placebo (P = 0.033). The cumulative percent healed after four and eight weeks of therapy for misoprostol versus placebo were: 83% vs 61% at four weeks and 96% vs 90% at eight weeks (P = 0.0028 and P = 0.0977, respectively by lifetable analysis). Relief of abdominal pain did not differ significantly between the treatment groups. Misoprostol significantly accelerates the healing of ibuprofen-, piroxicam-, or naproxen-induced gastric ulcers.
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PMID:Treatment of nonsteroidal antiinflammatory drug-induced gastric ulcers with misoprostol. A double-blind multicenter study. 147 30

Non-steroidal anti-inflammatory drug (NSAID) use is associated with gastro-duodenal erosions and ulcers. Bleeding and perforation are reported complications in NSAID users. Therapeutic recommendations for NSAID-induced gastroduodenal injury are necessary because of our rapidly growing geriatric population, a steady increase in prescriptions for NSAIDs, and the widespread use of over-the-counter NSAIDs. Studies seem to indicate that there is no relationship between acute NSAID-induced mucosal injury and potential damage from chronic NSAID ingestion. Ranitidine (150 mg) b.d. effectively reduces the incidence of duodenal ulcer in NSAID users, but the same dose does not reduce the incidence of gastric ulcer. Misoprostol is effective in reducing the incidence of gastric ulcer in NSAID users, although confirmatory data on its effectiveness in preventing NSAID-induced duodenal ulcer are lacking. In addition to anti-ulcer therapy, treatment of NSAID-induced ulcers includes discontinuing the drug, reducing the dose, or switching to a less potent NSAID. Longer courses of anti-ulcer treatment may be required to achieve expected healing rates when NSAIDs are not discontinued. Results of treatment of NSAID-related ulcers with currently available anti-ulcer medications vary. Several studies have shown that 150 mg ranitidine b.d heals both gastric and duodenal NSAID-induced ulcers. Sucralfate has also been shown to heal NSAID-induced duodenal ulcers. Misoprostol treatment of NSAID-induced ulcers is not well documented, although there are placebo-controlled data that substantiate its benefit in gastric ulcer patients not taking NSAIDs.
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PMID:Non-steroidal anti-inflammatory drug-induced gastroduodenal injury: therapeutic recommendations. 167 75

Synthetic prostaglandins of the E series have cytoprotective and gastric antisecretory actions. Both actions are relevant to their therapeutic usefulness in treating and preventing gastrointestinal mucosal diseases. Controlled clinical studies have shown prostaglandins to be effective treatment for gastric and duodenal ulcer disease. Although used widely in dozens of foreign countries, however, prostaglandins have not been approved by the United States Food and Drug Administration for use in the treatment of peptic ulcer disease. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased incidence of gastric and duodenal ulcers, gastrointestinal bleeding, and increased morbidity and mortality. Misoprostol, a prostaglandin E1 analogue, is effective in preventing and treating NSAID-induced mucosal damage and has been approved by the Food and Drug Administration for the prevention of NSAID-associated gastric ulcers. Controlled studies have not provided convincing evidence that H2-receptor antagonists or sucralfate prevents NSAID-induced gastric ulcer. Preliminary clinical studies indicate that some E-prostaglandins may also be effective in treating and/or preventing stress ulcer, cystic fibrosis, and hepatorenal syndrome and in improving graft survival in renal transplant patients receiving cyclosporine. Additionally, in vitro and animal studies suggest that prostaglandins may have therapeutic value in inflammatory bowel disease, and they may promote cartilage repair by an inhibitory action on interleukin-1. The latter finding could be of major relevance in preventing cartilage destruction in rheumatic patients. Significant side effects associated with the clinical use of prostaglandins include mild to moderate diarrhea and stimulation of uterine contraction during early pregnancy. Prostaglandins are effective for the treatment of peptic ulcer disease and, to date, are the only effective therapy for preventing the total spectrum of NSAID-induced mucosal damage. These compounds may also prove effective in treating various inflammatory disorders.
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PMID:Prostaglandins: an overview of the worldwide clinical experience. 181 16

Misoprostol (Cytotec, G.D. Searle & Company, Chicago, IL) is the first of a new class of orally administered prostaglandin analog drugs to be marketed in the United States. Misoprostol was approved for the prevention of gastric mucosal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDS) in high-risk patients. This represents a potentially important development in the pharmacotherapy of peptic ulcer disease. The purposes of this article are to review (1) the biochemistry, physiology, and pharmacology of prostaglandins, especially those synthesized by the stomach; (2) the potential role of prostaglandin deficiency in the pathophysiology of gastric ulcer disease; and (3) the role of prostaglandin analogs in the prevention and therapy of gastric ulcer disease and in other conditions. As the mechanism of action of these new drugs differs from that of the histamine H2-receptor antagonists (H2-blockers), prostaglandin analogs will, whenever possible, be compared with the H2-blockers [cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid) and famotidine (Pepcid)], currently the cornerstone of peptic ulcer therapy in this country.
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PMID:Prostaglandins and gastric ulcers: from seminal vesicle to misoprostol (Cytotec). 197 94

Evidence is accumulating that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is linked to ulceration of the stomach and duodenum and can cause significant, life-threatening ulcer complications. The mechanism of action seems to be both topical damage to the mucosal barrier and the systemic effect of a reduction in levels of mucosal prostaglandins. Patients especially at risk are the elderly, those with concomitant debilitating disease, those with a history of ulcers, and those taking corticosteroids. Histamine2 blockers are reported to significantly reduce the incidence of NSAID-induced duodenal ulcer, and misoprostol (Cytotec) has been shown to significantly reduce the incidence of NSAID-induced gastric ulcer. Prophylaxis with these agents should be considered for high-risk patients who need NSAID therapy to maintain a reasonable life-style.
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PMID:Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. An overview. 203 Oct 29

Prostaglandins have been shown to prevent the damage to the gastric and intestinal mucosa which has been induced by diverse necrotizing substances. These damaging stimuli increase the liberation of histamine from mast cells. Because of its well known effects on cellular permeability, histamine may serve the initial stimulus for mediating cellular damage. The aim of our study was to investigate the effect of misoprostol, a synthetic PGE1 analog, on tissue histamine concentration and mast cell counts after damage to the gastric mucosa induced by stress, histamine, aspirin and concentrated ethanol in guinea pigs. Misoprostol or its matching placebo were administered intragastrically 3 minutes prior to the ulcerogenic stimulus. After the induction of the injury, the animals were sacrificed, stomachs were examined for ulceration. Gastric and duodenal histamine concentrations were determined. Mast cells from these organs were stained and counted. All four ulcerogenic stimuli resulted in significant gastric ulcer formation. This ulcerogenic action was accompanied by a significant decrease in mucosal histamine concentration and mast cell counts. Misoprostol induced a dose-dependent inhibition of gastric damage, histamine depletion and mast cell destruction. These results indicate that the stabilization of mast cells by misoprostol is an important mechanism for its mucosal protective effects against ulcerogens.
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PMID:Misoprostol prevents damage to the gastric mucosa by stabilizing the mast cells. 244 10

Both misoprostol (synthetic PGE1 analog) and De-Nol (factor releasing endogenous prostaglandins in the gastric mucosa) can be useful in the treatment of patients with gastric ulcer resistant to cimetidine according to their gastroprotective properties. 64 patients whose gastric ulcer had not healed after 6 weeks of therapy with cimetidine in daily dose of 1000 mg were treated in a comparative short-term trial to assess the relative efficacy of misoprostol (Cytotec; Searle) in daily dose of 800 micrograms (I group; n = 32) and colloidal bismuth subcitrate (De-Nol; Gist-Brocades), four times a day in dose of 5 ml diluted with 15 ml of water (II group; n = 32). Both groups of patients were comparable according to age, sex, duration of ulcer disease, smoking habits, gastric acid secretion, ulcer size and localization in the stomach. The ulcer healing was controlled endoscopically after 2 and 4 weeks of the treatment. Healing rates after 2 weeks of therapy appeared to be 47% for misoprostol and 34% for De-Nol. After 4 weeks of therapy the healing rates were 72% with misoprostol and 63% with De-Nol. No statistically significant differences in the therapeutic efficacy were observed between two groups of the patients. No correlation was found between the ulcer healing rates and size of ulcer, its localization or smoking habits. The moderate side effects (transient diarrhea) were observed in 22% of patients treated with misoprostol. These findings suggest that misoprostol is as effective as De-Nol in the treatment of gastric ulcers resistant to cimetidine.
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PMID:[Misoprostol and de-nol in the treatment of patients with cimetidine-resistant stomach ulcer]. 251 27

Endogenous and exogenous prostaglandins mobilize gastroduodenal mucosal defenses which are compromised by inhibition of prostaglandin synthesis with non-steroidal anti-inflammatory drugs (NSAIDS). There is some evidence, conversely, that stimulation of endogenous prostaglandin synthesis by increasing precursor availability by dietary enrichment or by provoking its release may increase mucosal integrity. However, there are also non-prostaglandin defense mechanisms which can be elicited even when prostaglandin synthesis is profoundly depressed. Most (but not all) evidence suggests that gastric ulcer patients have deficient prostaglandin synthesis, though it is not clear whether this is a primary or secondary defect and the evidence on duodenal ulcer patients is incoherent. Prostaglandin analogues heal both gastric ulcers and duodenal ulcers, mainly as a result of acid inhibition. There is suggestive, but not conclusive, evidence that subsequent relapse may be retarded. Misoprostol has obtained a licensed indication for the prevention of NSAID-induced peptic ulcer on the basis of studies showing a reduced development of peptic ulcers and erosions over 4-8 weeks, implying that deficient endogenous prostaglandin levels can be replaced by exogenous administration.
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PMID:Prostaglandins: mucosal protection and peptic ulceration. 265 88

Misoprostol is an E1 prostaglandin analog. Most of the other synthetic prostaglandins that are being studied in advanced clinical trials for gastrointestinal diseases are E2 derivatives. Misoprostol has shown a dose-related antisecretory effect that lasted 3-5.5 hr. In addition, animal studies have shown cytoprotective properties that are being confirmed in clinical studies. Ulcer-healing trials using four times daily dosing appear to parallel the antisecretory dose-response curve up to a dose of 200 micrograms qid. Evidence presented in this supplement suggests a further increase in healing-rate response at 300 micrograms misoprostol qid. The misoprostol healing rates obtained in duodenal ulcer and gastric ulcer therapy at 200 micrograms qid are not significantly different from those seen in the same studies with cimetidine at a dose of 300 mg qid. No significant rebound in recurrence has been observed during follow-up for 12 months after short-term 100- and 200-micrograms qid misoprostol treatment. The most frequent adverse effects are dose-related diarrhea and abdominal cramping, which are transient in most patients and have not caused a significant problem in clinical use. There is also a tropic effect on the pregnant uterus, which was observed in a special pharmacologic clinical study. No significant abnormalities have been detected in clinical laboratory tests or gastric biopsies. There have also been no adverse effects noted on blood pressure, pulse, platelets, the immune system, pulmonary function, gastrointestinal hormones, or the endocrine system. These previously discussed characteristics of misoprostol, and current data, suggest that this prostaglandin E1 derivative may be an important addition to the treatment of peptic ulcer disease.
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PMID:Overview of misoprostol clinical experience. 308 Feb 88


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