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)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used of all drugs and are the most common medications used by persons aged 65 years or more. NSAIDs have a number of side effects, of which the most prevalent and serious is gastrointestinal (GI) toxicity. GI side effects of NSAIDs range from dyspepsia and gastroduodenal ulcers to serious, potentially fatal GI complications including bleeding and perforation. Serious GI complications often lack warning signs; knowledge of risk factors for NSAID-related gastropathy can identify patients at high risk, allowing for initiation of the appropriate therapeutic intervention. Risk factors include advanced age, NSAID dose, prior GI complications, infection with Helicobacter pylori, and use of corticosteroids and anticoagulants. There are few well-established strategies to prevent GI complications in NSAID users. Risk assessment and cotherapy with acid suppressors (H2-receptor antagonists and proton pump inhibitors) or prostaglandin replacement (misoprostol) and H pylori eradication are beneficial. Cyclooxygenase-1 (COX-1) is a key enzyme in gastroprotective mucosal defenses, and the best way to prevent GI toxicity is to avoid drugs that inhibit COX-1. Clinical studies of the COX-2-selective inhibitors rofecoxib and celecoxib have demonstrated efficacy equivalent to nonselective NSAIDs with lower rates of GI side effects (for example, incidence of endoscopic ulcers equivalent to placebo). Selective COX-2 inhibitors (coxibs) provide effective treatment of pain and inflammation while reducing risk of gastropathy.
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PMID:Gastrointestinal safety and tolerability of nonselective nonsteroidal anti-inflammatory agents and cyclooxygenase-2-selective inhibitors. 1208 91

Non-steroidal anti-inflammatory drugs (NSAID) belong to the most commonly used drugs worldwide. NSAIDs can cause serious side effects to the gastrointestinal tract. During NSAIDs treatment 10-12% patients suffer from dyspepsia. Up to 1% patients develop severe gastrointestinal complications (ulcer, bleeding, perforation). Any part of gastrointestinal tract could be affected. In oesophagus, NSAIDs can cause oesophagitis of fibrous stricture. NSAID gastropathy can be detected in 40% patients chronically treated with NSAIDs. NSAIDs toxic injury to small and large bowel is frequent but only seldom properly recognised. Serious hepatic lesions are rare. There is no fully reliable and sure prophylaxis or treatment of NSAIDs impairment of to the gastrointestinal tract. Rate of side effects can be reduced by reasonable prescriptions and by primary and secondary prophylaxis. Low rate of side effects is associated with the use of pro-drugs (compound is metabolised to an active substance after absorption from the gastrointestinal tract). New promising drugs were developed with dual action (5-lipoxygenase- and COX-inhibition) and NSAID releasing NO (nitronaproxen, nitrophenac). Specific COX-2 inhibitors (coxibes) provide comparable anti-inflammatory and analgesic effect but the risk of serious side effects to the gastrointestinal tract is significantly lower (when compared with non-specific NSAIDs). Beside harmful effects, NSAIDs are powerful tool in chemoprevention of colorectal cancer.
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PMID:[Effects of nonsteroidal anti-inflammatory agents on the gastrointestinal tract]. 1256 74

Dyspepsia is a common problem that is important from the perspectives of both patient health and economics. While there has been variability in the definitions used to describe dyspepsia, there have also been few standardized outcomes tools designed to measure dyspepsia-related health, especially in relation to changes in dyspepsia over time. An evaluative tool was developed, the Severity of Dyspepsia Assessment (SODA), which takes into account the multidimensional nature of dyspepsia using three scales (Pain, Non-pain Symptoms, and Satisfaction with Dyspepsia-related Health) and demonstrates good psychometric properties with respect to validity, reliability and sensitivity to change in the measurement of dyspepsia-related health. Although originally developed for the assessment of uninvestigated dyspepsia, the validation of SODA for use in clinical trials suggested its ability to compare treatment effects of non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2-specific inhibitors. In comparative trials of celecoxib or valdecoxib with non-specific NSAIDs, COX-2-specific inhibitors were demonstrated to have superior dyspepsia tolerability than non-specific NSAIDs. These data demonstrate that SODA is an effective instrument for measuring dyspepsia-related health with a broad range of applications.
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PMID:Measuring dyspepsia-related health in randomized trials: the Severity of Dyspepsia Assessment (SODA) and its use in treatment with NSAIDs and COX-2-specific inhibitors. 1458 16

Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can each result in gastric or duodenal ulcer(s) and ulcer complications. Together, H. pylori infection and NSAIDs account for approximately 90% of peptic ulcer disease. In 2003, the results of studies suggest, and guidelines recommend, the careful selection of anti-inflammatory drugs - NSAIDs or selective COX-2 inhibitors (coxibs) based upon patients gastrointestinal history and use of aspirin therapy. Testing for, and cure of, H. pylori infection is recommended in patients prior to the initiation of NSAID therapy and in those who are currently receiving NSAIDs and have a history of dyspepsia, peptic ulcer or ulcer complications. For patients who present with peptic ulcer bleeding but require NSAIDs long-term, H. pylori eradication therapy should be considered, followed by continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless of which kind of NSAID (nonselective NSAID /coxib) is being prescribed. Routine testing for, and eradication of, H. pylori infection has not been recommended for current takers of NSAIDs with no or low risk of complications. The management of patients taking low-dose aspirin is complex, but eradication of H. pylori infection alone in those with a past history of bleeding does not guarantee complete protection and therefore a proton pump inhibitor should also be given. The success of eradication therapy should always be confirmed, because of the risk of ulcer recurrence and bleeding in H. pylori-infected patients who require anti-inflammatory treatments.
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PMID:Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. 1472 73

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used to treat arthritis but are associated with adverse gastrointestinal events. While the selective COX-2 inhibitors show fewer gastrointestinal complications than NSAIDs, they may not be suitable for all patients and one of them has been associated with serious thrombotic cardiovascular events. Furthermore, many arthritis patients are at high risk of coronary artery disease and take low-dose aspirin, which is also associated with adverse gastrointestinal events. Proton pump inhibitor (PPI) therapy has been shown to be effective in reducing the risk of gastrointestinal complications in this patient population. Recent randomized clinical trials have also shown that pantoprazole therapy is effective in the healing of NSAID-induced gastrointestinal damage. Several studies have also demonstrated that pantoprazole is effective in preventing the development of gastrointestinal lesions in patients with continuous NSAID intake. The use of PPIs in combination with nonselective NSAIDs has also been found to be beneficial in patients at high risk for rebleeding and reduces the incidence of dyspepsia. Finally, the combination of a COX-2 inhibitor with a PPI has shown promise in patients with previous NSAID-related gastrointestinal complications who are at high risk for reinjury.
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PMID:Understanding NSAID-PPI-COX-2 interrelationships. 1519 Mar 84

Upper gastrointestinal symptoms are highly prevalent; usually those consulting have multiple symptoms, confounding management. Here, common clinically relevant management issues are considered based on the best available evidence. Regardless of the presenting symptoms, determine if there are any alarm features; these have a low positive predictive value for malignancy but all patients with them should be referred for prompt upper gastrointestinal endoscopy. Ask about medications; of most importance are the non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and COX-2 selective. Try to ascertain if the symptom pattern suggests gastro-oesophageal reflux disease (GERD) or not. Dominant heartburn, however, may be of limited value; if the background prevalence of GERD is 25% and the patient complains of dominant heartburn, then the likelihood that such a patient has GERD as identified by 24-h oesophageal pH testing is only just over 50%. If reflux disease is strongly suspected and there are no alarm features, give an empirical trial of a proton pump inhibitor (PPI). Symptoms cannot separate adequately functional from organic dyspepsia. Endoscopy in dyspepsia with no alarm features is more costly than an empirical management approach. H. pylori testing and treatment remains in most settings the preferable initial choice for managing dyspepsia without obvious GERD. However, a PPI trial may offer a similar outcome and may be preferable in low H. pylori prevalence areas; head-to-head management trials in primary care are lacking.
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PMID:What the physician needs to know for correct management of gastro-oesophageal reflux disease and dyspepsia. 1533 10

Non-steroidal anti-inflammatory drugs (NSAIDs) are the major recognized cause of iatrogenic disease, and may cause 100 000 deaths per annum through peptic ulcer complications. A number of risk factors can be identified that indicate patients at high risk. These patients can be managed by substitution of a COX-2 inhibitor or by prophylaxis with a proton pump inhibitor (PPI). Because risk factors that render patients at high risk of ulcer complications also act in the absence of NSAID use, PPI prophylaxis (or Helicobacter pylori eradication where H. pylori is the risk factor) have much to offer and controlled studies show that the incidence of recurrent peptic ulcer bleeding can be reduced substantially by PPI co-administration. Substitution of COX-2 inhibitors also has much to offer, arguably most in those without risk factors (although regulatory authorities do not accept this argument). Recent data show that PPI and COX-2 inhibitors can play complementary roles in the management of patients with moderate to severe dyspepsia and at high risk of ulcer complications.
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PMID:Non-steroidal anti-inflammatory drugs: who should receive prophylaxis? 1533 14

NSAIDs-induced dyspepsia occurs in 10 to 30% of patients treated with NSAIDs, leading to discontinuation of treatment in 5 to 15%. Gastrointestinal tolerability of COX-2 selective inhibitors is better than for non-selective NSAIDs. Helicobacter pylori infection does not influence gastrointestinal tolerability of NSAIDs. Therefore, patients should not be tested and treated for H. pylori infection unless they have a history of peptic ulcer. Symptoms of NSAIDs-induced dyspepsia are poorly correlated with gastroduodenal mucosal damage. Therefore, upper gastrointestinal endoscopy should be performed only if symptom relief is not achieved with the first line empirical treatment and/or if symptoms suggestive of complications, such as bleeding, develop. Proton pump inhibitors appear to be the treatment of choice for NSAIDs-induced dyspepsia.
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PMID:[Treatment of NSAIDs related dyspepsia]. 1536 77

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.
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PMID:Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. 1545 29

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce symptoms of dyspepsia and peptic ulcer disease in up to 50% and up to 20%, respectively, of individuals taking them. Risk factors for NSAID-related gastric injury include age >70 years, history of ulcer disease, use of multiple agents (e.g., > or =2 NSAIDs, or an NSAID plus aspirin--even at cardioprotective doses), high doses of an NSAID, and concurrent use of corticosteroids or anticoagulants. In NSAID users, infection with Helicobacter pylori can produce additive or synergistic gastric mucosal injury. Several clinical strategies can decrease the risk for dyspepsia, ulceration, and the more serious complications in NSAID users. Proton pump inhibitor (PPI) co-therapy has been shown to lower the incidence of dyspepsia in those taking NSAIDs. In those with an active ulcer, PPI therapy produces ulcer healing even in "tough-to-treat" individuals who require ongoing NSAID therapy. Maintenance of ulcer healing is significantly greater in those who receive ongoing PPI treatment compared with placebo, and adverse events and treatment withdrawals are fewer compared with their occurrence in persons treated with misoprostol. In those not receiving aspirin therapy, the use of an NSAID that is a selective inhibitor of cyclooxygenase (COX)-2 may result in fewer gastrointestinal symptoms compared with a traditional agent; however, studies have failed to show any decrease in healthcare resource utilization (including outpatient or emergency room visits, hospitalization rate, or use of any resource) with COX-2-selective therapy.
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PMID:Prevention of nonsteroidal anti-inflammatory drug-associated gastrointestinal symptoms and ulcer complications. 1547 55


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