Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) are at an increased risk of gastroduodenal erosions, ulcers, and the associated complications of haemorrhage, perforation, and death. Many NSAID associated ulcers that bleed or perforate have been asymptomatic until the time of presentation and conversely many patients with dyspepsia do not have ulcers. Symptoms are a poor guide to the presence of an ulcer. During continued treatment with NSAIDs misoprostol is the best choice for NSAID induced gastroduodenal damage; it achieves higher rates of healing than other drugs in these circumstances. Misoprostol is superior to other drugs in the prevention of gastric damage but misoprostol and H2 antagonists are of similar benefit in the duodenum. Prophylactic studies have all used endoscopic damage as an endpoint, and much larger studies will be needed to show an effect of misoprostol on the incidence of ulcer complications. There are no clear guidelines as to which patients should receive prophylactic treatment with misoprostol but those particularly at risk of ulcer complications--that is, those with previous peptic ulceration, the elderly, medically unfit, patients receiving large doses of NSAIDs, and those patients receiving steroids in addition to NSAIDs--should be considered.
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PMID:Misoprostol in the prevention of gastroduodenal damage in rheumatology. 141 45

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.
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PMID:Overall safety of Arthrotec. 143 22

One hundred and thirty-seven consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were randomly allocated to double-blind treatment with 400-micrograms misoprostol tablets twice daily or placebo for 4 weeks. Misoprostol had a significant worsening effect on epigastric pain, nausea, meteorism, lower abdominal pain, and diarrhoea, as compared with placebo. The fact that symptoms in patients with NUD and EPC were exacerbated by an antisecretory dose of misoprostol indicates that the symptoms are largely unrelated to gastric acid.
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PMID:Misoprostol treatment exacerbates abdominal discomfort in patients with non-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-controlled, multicentre study. 212 24

Although therapeutically beneficial, nonsteroidal anti-inflammatory drugs are associated with serious gastrointestinal side effects, including ulceration, hemorrhage, and perforation. Endoscopic studies indicate that up to 30% of chronic NSAID users will develop gastroduodenal ulceration. Various case-control studies have reported an association between ulcer-related complications or deaths and NSAID use. An imprecise correlation has been found to exist between the presence of NSAID-induced gastrointestinal damage and symptoms, such as dyspepsia and pain. It is now thought that the major deleterious effects of NSAIDs on the gastrointestinal tract are related to the ability of systemically absorbed NSAIDs to alter gastric and duodenal defense mechanisms, primarily via inhibition of mucosal prostaglandin synthesis. Although various therapeutic agents have been investigated for their ability to prevent NSAID-induced ulcers, only the prostaglandin analogue misoprostol has been shown to significantly reduce the incidence of both gastric and duodenal ulcers in NSAID users. Recently, the Misoprostol Ulcer Complications Outcomes Safety Assessment trial demonstrated that misoprostol also reduces the most serious complications of NSAID-induced ulcers, namely bleeding, perforation, and gastric outlet obstruction.
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PMID:Considerations for nonsteroidal anti-inflammatory drug therapy: safety. 879 7

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

Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non-NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID-associated gastrointestinal complications. The exact association between Helicobacter pylori infection and NSAID-related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID-using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID-associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID-associated ulcers among patients who cannot discontinue NSAID therapy.
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PMID:Review article: nonsteroidal anti-inflammatory drug-associated gastrointestinal complications--guidelines for prevention and treatment. 1054 41

It is rather difficult to choose a drug to treat nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathies in patients with rheumatic diseases, which primarily makes it necessary to use antiulcerous treatment as part of continuous NSAID therapy. Detecting upper gastric ulcers or erosions in many patients admitted to a rheumatology hospital for exacerbation of the underlying disease cannot cause NSAID to be discontinued even temporarily as this may lead to a significant deterioration and progression of the joint syndrome. The aim of the study was to evaluate the efficiency of 2-week treatment with misoprostol (Cytotec), 800 micrograms/day, and omeprasole (Omez), 40 mg/day, for NSAID-induced gastropathy in 63 patients with rheumatic diseases. The study has indicated that the use of Omez seems to be more advisable than that of Cytotec in the treatment of NSAID-induced gastropathy if it is necessary to continue to treat the patient with a whole range of antirheumatic drugs. Equally effective in healing ulcers and erosions, Omez is much better tolerated and able to rapidly relieve gastralgias and dyspepsia. It seems that the use of Cytotec for NSAID-induced gastropathy with a great deal of side effects and relatively less efficiency borne in mind may be limited because of cases of inefficiency of proton pump inhibitors.
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PMID:[Omeprazole and misoprostol for NSAID-induced gastropathies: comparative efficiency of their short-term treatment]. 1151 Jan 88

The use of specific agents to heal mucosal lesions or to prevent non-steroidal anti-inflammatory drug toxicity, has focused upon two approaches: replacement of prostaglandin deficiency and inhibition of acid secretion. Acid suppression with traditional ulcer healing doses of H2-blockers is effective in healing gastric and duodenal ulcers upon discontinuation of the offending drug. In the event the non-steroidal anti-inflammatory drug must be continued, the use of H2-blockers is associated with a decrease in the healing rate. In long-term prevention studies, H2-blockers significantly reduce duodenal ulcer rates, but are ineffective in reducing gastric ulceration. More potent acid inhibition with a double-dose of H2-blockers (famotidine 80 mg daily, ranitidine 600 mg daily) may reduce the risk of gastric and duodenal ulcers. Marked acid suppression with proton pump inhibitors (omeprazole 20-40 mg, lansoprazole 30 mg daily) also appears to be very effective in healing gastric and duodenal ulcers in patients continuing the offending drug as well. An analysis of pooled data from comparative studies on omeprazole vs ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the proton pump inhibitor, ranging from 10 to 40%. In long-term prevention studies, omeprazole (20 mg daily) and pantoprazole (40 mg daily) have also been shown to reduce the risk of gastric and duodenal ulcers and non-steroidal anti-inflammatory drug-related dyspepsia. Current data from recent comparative studies of omeprazole (20 mg daily) vs ranitidine (150 mg daily) and misoprostol (200 microg daily) showed that, after 6 months' follow-up, the proton pump inhibitor was significantly superior to control drugs in reducing the risk both of gastric and duodenal ulcer. Misoprostol (at doses ranging from 400 microg to 800 microg/day) is an effective form of therapy for preventing non-steroidal anti-inflammatory drug-induced gastroduodenal lesions. However high-dose misoprostol only, seems adequate for the prevention of ulcer complications, mainly in high-risk non-steroidal anti-inflammatory drug users. Thus, available data are undoubtedly in favour of the proton pump inhibitors as well tolerated and effective drugs in the prophylaxis and treatment of non-steroidal anti-inflammatory drug-related mucosal lesions in the gastrointestinal tract.
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PMID:Prophylaxis and treatment of non-steroidal anti-inflammatory drug-induced upper gastrointestinal side-effects. 1182 62

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found with an endoscopy in 15%-30% of patients who are using NSAIDs regularly, and the annual incidence of upper gastrointestinal (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs. H2-receptor antagonists when used at standard doses are not effective at preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol effectively decreases NSAID-induced ulcers and GI complications, but issues of compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia) may limit its use. Once-daily therapy with proton pump inhibitors has been documented to significantly decrease the development of NSAID-associated ulcers in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and reduce upper GI symptoms in NSAID users.
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PMID:The role of proton pump inhibitors in NSAID-associated gastropathy and upper gastrointestinal symptoms. 1467 12

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory, analgesic, and anti-pyretic effects, whereas low-dose aspirin (also an NSAID) is used for cardiovascular prophylaxis. The main concern limiting use of these drugs is their gastrointestinal (GI) toxicity. GI side effects include ulcers (found at endoscopy in 15%-30% of patients using NSAIDs regularly), complications such as upper GI bleeding (annual incidence of 1.0%-1.5%), and development of upper GI symptoms such as dyspepsia (occurring in up to 60% of patients taking NSAIDs). Histamine-2 receptor antagonists are not effective at preventing NSAID-induced gastric ulcers when used at standard doses, although they can decrease upper GI symptoms. Misoprostol effectively decreases NSAID-induced ulcers and GI complications but is used infrequently in the United States-perhaps because of issues of compliance (multiple daily doses) and side effects (eg, diarrhea, dyspepsia). Once-daily proton pump inhibitor (PPI) therapy also decreases the development of NSAID-associated ulcers and recurrent NSAID-related ulcer complications; it also decreases upper GI symptoms in NSAID users. In patients using aspirin, the addition of a cyclooxygenase-2-specific inhibitor appears to significantly increase GI risk to the level of a nonselective NSAID; aspirin plus a nonselective NSAID appears to increase GI risk still higher. Patients taking low-dose aspirin who have risk factors for GI complications (including concomitant nonselective NSAID therapy) should receive medical co-therapy, such as a PPI.
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PMID:Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs--nice or necessary? 1558 Jan 45


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