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)

Misoprostol was provided on a humanitarian basis to 157 patients with severe, often life-threatening, refractory upper gastrointestinal (UGI) disease not managed by available medical therapy (cimetidine, ranitidine, antacids, sucralfate, and/or prior surgery). A total of 162 separate clinical treatment courses were evaluated in the 157 patients for the period May 1, 1981 to May 6, 1986. Misoprostol was administered orally or via nasogastric tube, 800 micrograms to 1,200 micrograms daily in four to six divided doses, for periods of from one day to 17 months. Patients were considered to have a favorable clinical outcome if they achieved significant improvement in symptoms, hemorrhagic status, or appearance of their condition on endoscopy. Favorable clinical outcomes were observed in 52 of 83 treatment courses (63 percent) involving UGI hemorrhage and in 44 of 79 treatment courses (56 percent) for long-standing nonhemorrhagic UGI disease. A total of 116 treatment courses were for patients with a single UGI entry diagnosis; 28 treatment courses were for patients with two UGI entry diagnoses; four courses were for patients with three UGI entry diagnoses; and 14 treatment courses were for miscellaneous UGI entry diagnoses. Treatment outcomes were analyzed by the four most commonly treated UGI entry diagnoses; patients who had an initial diagnosis of refractory duodenal ulcer (n = 28), refractory gastric ulcer (n = 41), reflux esophagitis (n = 23), or hemorrhagic gastritis (n = 63) had favorable clinical outcomes of 71 percent, 58 percent, 61 percent, and 62 percent, respectively. Misoprostol was well tolerated, with the most common adverse experience being mild to moderate diarrhea. It is concluded that in humanitarian clinical trials, misoprostol was frequently associated with symptomatic relief, with improvement in UGI hemorrhage, or with endoscopic improvement in severe UGI disease that had proven refractory to available medical therapy.
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PMID:Humanitarian use of misoprostol in severe refractory upper gastrointestinal disease. 311 46

Misoprostol, a synthetic prostaglandin E1 (PGE1) methyl ester analog has potent antisecretory and cytoprotective effects on the gastric and duodenal mucosa which should make it an effective drug in the treatment of gastric and duodenal ulcer. In two multicenter, randomised, double-blind, controlled studies involving over 900 patients with endoscopically proven benign gastric ulcer and in six similar studies involving over 2000 patients with active duodenal ulcers, differing doses of misoprostol have been compared with either placebo therapy or with conventional doses of cimetidine. In these studies misoprostol 800 mcg daily given as two or four divided doses has been shown to produce rates of complete ulcer healing and pain relief which were significantly superior to placebo therapy and comparable to those achieved with cimetidine. Drug related adverse effects were infrequent. A dose related diarrhea occurred in a small proportion of patients which seldom necessitated suspension of therapy. Because of the known uterotropic effect of prostaglandins the drug should not be used in pregnant women or women of child bearing age unless they are using adequate contraceptive measures. No clinically significant adverse, hematological or biochemical effects have been reported. Two studies suggested that misoprostol reduced the adverse effect of smoking on the healing of duodenal ulcer. In addition, misoprostol has been shown to protect the gastro-duodenal mucosa from the damaging effects of alcohol and non-steroidal anti-inflammatory drugs. This action may prove of value in the treatment of ulcer patients who are inveterate smokers, alcohol users or who are compelled to consume non-steroidal anti-inflammatory drugs for pain relief from rheumatic and allied diseases.
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PMID:Misoprostol in peptic ulcer disease. 312 78

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1 (PGE1) is both a powerful inhibitor of gastric secretion and is able to protect the gastroduodenal mucosa from damage produced by alcohol, aspirin, naproxen and tolmetin. The results of 12 double-blind, randomized, placebo- and cimetidine-controlled trials involving 4000 patients have been reviewed here and show that misoprostol, given in a dosage of 800 micrograms daily in two or four divided doses, is able to produce rates of complete ulcer healing and pain relief in both gastric and duodenal ulcer which are significantly superior to placebo therapy and comparable to those achieved with high or conventional doses of cimetidine. One further large trial has shown that misoprostol is able to heal a significant proportion of duodenal ulcers refractory to treatment with H2 receptor antagonists. In the compromised patient, two trials have suggested that misoprostol is able to abolish the adverse effects of smoking on duodenal ulcer, although this effect was not apparent in the gastric ulcer trials or in other duodenal ulcer trials. Similarly, while in volunteers pretreatment with misoprostol is able to protect the gastric mucosa from alcohol damage, there is little clinical evidence to support improved ulcer healing in the patient who abuses alcohol. Further studies in these areas should be conducted. Misoprostol could well have an important role to play in the protection of the gastroduodenal mucosa from damage produced by non-steroidal anti-inflammatory drugs (NSAIDs) in arthritic patients compelled to take these drugs for long periods. A series of double-blind placebo-controlled trials in healthy volunteers have shown that pretreatment with, or simultaneous administration of, 800 micrograms daily of misoprostol, reduces significantly mucosal damage produced by aspirin, tolmetin and naproxen. Two controlled clinical trials in a large number of arthritic patients have shown firstly, that misoprostol 800 micrograms daily is able to reduce significantly aspirin-induced mucosal bleeding as compared with placebo and secondly, in an endoscopically, placebo-controlled trial that it reduced significantly the frequency and severity of aspirin-induced mucosal lesions, accelerated the healing of erosions and ulcers and in other patients was able to protect the undamaged mucosa from injury. Misoprostol is well tolerated--a dose related, usually self limiting, diarrhoea occurred in a small proportion of patients but only rarely enforced withdrawal. Because of its uterotropic effects misoprostol should not be given to women of child bearing age unless they are taking adequate contraceptive measures. It has no other systemic effects and no clinically significant adverse haematology or biochemical abnormalities, or drug interactions have been reported. It does not seem to induce hypergastrinaemia. Misoprostol is, therefore, a safe and effective drug in the treatment of chronic peptic ulcer and could have a beneficial action in duodenal ulcers refractory to treatment with H2-receptor antagonists. It could benefit compromised groups of ulcer patients who are smokers or alcohol users amd certainly has been shown to protect the gastroduodenal mucosa against damage induced by NSAIDs in healthy volunteers and arthritic patients.
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PMID:The therapeutic efficacy of misoprostol in peptic ulcer disease. 313 82

Misoprostol, a synthetic prostaglandin E1 methyl ester analog with gastric antisecretory and cytoprotective properties, prevents the development of acute experimental gastric and duodenal ulcers in various animal models. This study was designed as a multicenter randomized double-blind parallel-group comparison of the effects of two dosage strengths (25 and 100 micrograms q.i.d.) of orally-administered misoprostol and placebo on the healing of endoscopically-proven benign gastric ulcer in 299 out-patients. Safety was evaluated by comparison of pre- and post-treatment physical examinations, clinical laboratory tests, gastric antral biopsies and monitoring of adverse experiences. A statistically significant difference in gastric ulcer healing rate was seen at eight weeks among the treatment groups in the Intent-to-Treat Cohort: misoprostol 100 micrograms (62.0%), misoprostol 25 micrograms (50.0%), placebo (44.7%). The proportion of subjects healed in up to eight weeks of treatment was greatest in the misoprostol 100 micrograms group in all cohorts. Ulcer pain decreased in all treatment groups in successive weeks and there were no statistical differences among any of the three treatment groups. Diarrhea was the most frequently reported adverse experience: misoprostol 100 micrograms (9.8%), misoprostol 25 micrograms (7.7%), placebo (1.9%). The diarrhea was mild and self-limiting despite continued use of misoprostol. Overall evaluation of gastric antral biopsies showed no adverse changes in the morphology of the antral mucosa. We conclude that misoprostol 100 micrograms q.i.d. for up to eight weeks is safe and effective in the treatment of benign gastric ulcer.
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PMID:Healing of benign gastric ulcer. A placebo-controlled comparison of two dosage regimens of misoprostol, a synthetic analog of prostaglandin E1. 393 50

An endoscopic screening was carried out during the period between July 1989 and December 1991 in the Municipality of Roccagorga (LT) in order to: a) evaluate the presence of various forms of gastritis and pre-cancerous lesions; 2) verify the effect of the administration of prostaglandins (Misoprostol) on the evolution of superficial chronic gastritis (CG). A total of 468 endoscopy were performed (17% of the population aged between 20 and 75 years old). 22% of the subjects examined were found to be endoscopically normal; 34% presented symptoms of mild esophagitis and 4% of moderate esophagitis. The prevalence of duodenal ulcer was 10.6% and gastric ulcer 3.4%. Gastric carcinoma was diagnosed in 6 patients (1.2%). 8.5% of patients were found to have atrophic CG and 15.3% superficial CG. Thirty-six patients with superficial CG were randomly divided into two groups: A) treated with Misoprostol 600 mg/day for 6 months; B) controls (placebo). The administration of Misoprostol did not influence the evolution of CG, whereas it caused a reduction in the incidence of type 1 intestinal metaplasia. Misoprostol also led to an improvement in dyspeptic symptoms. The results of the present study do not suggest a role of prostaglandins in the natural evolution of CG.
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PMID:[Chronic gastritis and prostaglandins. Results of endoscopic screening]. 784 44

Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) almost invariably cause acute gastroduodenal injury and probably account for approximately 12,000 ulcer bleeding episodes and 1200 deaths per annum in the United Kingdom. Clinically significant intestinal toxicity is also recognized but less clearly defined. The main risk factors for NSAID-related peptic ulcer complications are age, past history, use of higher risk individual NSAIDs, drug dose, concurrent use of warfarin or corticosteroids. The underlying reason for NSAID use and Helicobacter pylori status is not clearly associated with increased risk. Whether NSAIDs cause drug-induced non-ulcer dyspepsia is also controversial. Acute injury occurs more readily with aspirin than with non-aspirin NSAIDs, and the spectrum of acute injury is of little value in predicting clinically significant end points in comparison with different NSAIDs. However, acute studies of co-prescribed protective agents are highly predictive of performance in clinical practice. Gastric mucosal integrity is maintained by the interplay of three protective networks: prostaglandin synthesis, nitric oxide synthesis and the activity of the enteric nervous system. Aspirin and NSAIDs act by inhibiting prostaglandin synthesis catalysed by two cyclooxygenase enzymes. Most existing NSAIDs are unselective and inhibit the activity of the constitutive cyclooxygenase (COX) 1 enzyme in the stomach as much as the cyclooxygenase (COX) 2 enzyme which is induced at sites of inflammation such as joint disease. There are, however, prospects for selective cyclooxygenase 2 inhibitors. Some NSAIDs, particularly aspirin, have additional topical toxicity, which may in part reflect mucosal trapping. Some data favor an effect of NSAIDs in inhibiting mitochondrial oxidative phosphorylation. The principal physiological mechanisms which are compromised by NSAID use are mucosal blood flow, secretion of mucus and bicarbonate and maintenance of a hydrophobic mucosal surface. Animal data suggest that polymorphonuclear leukocytes (PMNs) are important for acute damage though the relevance to humans has yet to be established. As well as damaging the mucosa, NSAIDs impair ulcer healing and are associated with reduced epithelial proliferation and evidence of diminished angiogenesis. An interaction between prostaglandins and growth factors, as well as the synthesis of antiproliferative products of arachidonic acid metabolism may be involved. Healing of NSAID ulcers by conventional doses of H2 antagonists is slow and H2 antagonists are poor at preventing gastric ulcer development or recurrence. These problems can be overcome by the use of more potent acid suppression. Misoprostol heals NSAID-associated ulcers, though whether healing is as fast as with non-NSAID ulcers has not been formally established. Misoprostol is effective prophylactic treatment but has a significant incidence of adverse events, particularly diarrhoea. Misoprostol has been reported to prevent ulcer complications, and in endoscopic studies has been superior as prophylaxis to standard dose ranitidine. Results of its efficacy compared to proton-pump inhibitors are awaited. For many patients appropriate management is avoidance of NSAIDs or use of less potent/toxic alternatives such as ibuprofen. Reductions in prescribing arising from a prior authorization scheme show that this can be achieved. For high-risk patients requiring continuing NSAID use co-prescription of omeprazole or misoprostol should be considered.
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PMID:Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. 889 49

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

Misoprostol effectively prevents nonsteroidal anti-inflammatory drugs (NSAID)-induced gastric ulcer and is the only agent currently indicated for this purpose. In addition, misoprostol is effective as prophylaxis against NSAID-induced duodenal ulcer. Because of the widespread use of NSAIDs, the cost of routine misoprostol prophylaxis would be high, and thus its pharmacoeconomic evaluation is an important factor in assessing the most appropriate role of misoprostol in this group of patients. Current cost-benefit analyses undertaken in major European centres and the US have generally indicated that, depending on initial assumptions, misoprostol prophylaxis over a 3-month period is cost-saving in patients with osteoarthritis taking NSAIDs. The net savings (costs) realised were dependent on several variables, including the acquisition cost of misoprostol, silent ulcer rate and patients' compliance. Importantly, misoprostol prophylaxis was consistently more cost-beneficial in elderly patients aged greater than 60 to 65 years than in their younger counterparts. In contrast, in one study misoprostol was found to reduce patients' quality of life and, although misoprostol therapy is potentially cost-saving to society, patients generally preferred no therapy. A single study assessing the cost-effectiveness of misoprostol prophylaxis in preventing ulcerative complications concluded that primary treatment was not an economically viable option for all NSAID users. Misoprostol was most cost-effective in the prevention of recurrent or secondary gastric ulcer complications in 'high-risk' patients, for example patients aged over 60 years and patients with rheumatoid arthritis. Thus, although there are areas of interest awaiting further pharmacoeconomic investigation, misoprostol prophylaxis appears to be cost-effective in elderly and high risk patients receiving NSAIDs. Additionally, misoprostol prophylaxis is cost-saving in elderly patients with osteoarthritis requiring NSAID therapy.
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PMID:Misoprostol: pharmacoeconomics of its use as prophylaxis against gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs. 1014 62

The aim of the review was to examine the effectiveness of misoprostol as co-therapy in the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. The outcomes assessed were the number of patients in whom a gastric ulcer developed, the number of patients in whom gastric lesions developed. The number of patients in whom a duodenal ulcer developed and the number of patients in whom duodenal lesions developed. The weighted average baseline risks for gastric ulcers were found to be 3.8% and 6.8% with short- and long-term non-steroidal anti-inflammatory drug treatment, respectively. Misoprostol treatment resulted in a significant (p < 0.05) risk reduction of gastric ulcer in the short-term (pooled RD = 13.3%; 95% confidence interval -25.7%, -0.9%) and in the long-term (RD = -8.4%; 95% confidence interval -17.7%, -1.0%) non-steroidal anti-inflammatory drug treatment. The weighted average baseline risks for duodenal ulcers were found to be 3% and 4% with short- and long-term non-steroidal anti-inflammatory drug treatment, respectively. Misoprostol did not significantly reduce the risk of duodenal ulcers with short treatment (RD = -2.0%; 95% confidence interval -5.7%, 1.6%). Treatment was effective in the long-term non-steroidal anti-inflammatory drugs therapy (RD = 3.4%; 95% confidence interval -5.8%, -0.1%, p < 0.001). The number of patients needed to be treated to prevent 1 person from developing a gastric ulcer within 2 weeks of non-steroidal anti-inflammatory drug therapy was found to range from 35, when baseline risk was 3%, to 3 when the baseline risk was higher, say 40%. The corresponding number of patients needed to be treated for gastric ulcer prevention in long-term studies ranged from 47 to 5. The number of patients needed to be treated for prevention of duodenal ulcer with misoprostol in short-term studies ranged from 36 to 4 and in the long-term trials form 47 to 8. In conclusion, a rational approach to treat only high risk patients is recommended.
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PMID:Non-steroidal anti-inflammatory drug gastropathy: clinical results with misoprostol. 1037 71


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