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

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.
 ...
PMID:Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. 889 49

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibiting cyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with improved tolerability. In volunteers, indomethacin 75 mg, but not meloxicam 7.5 mg, inhibited renal prostaglandin E2 excretion and platelet aggregation (COX-1 mediated effects). Double-blind, randomized trials in osteoarthritis and rheumatoid arthritis patients have shown equivalent antiinflammatory efficacy among meloxicam 7.5 mg or 15 mg and diclofenac 100 mg, naproxen 750 mg, and piroxicam 20 mg. In a double-blind, placebo-controlled trial, meloxicam (7.5 or 15 mg) caused less endoscopically detected gastrointestinal (GI) damage (Lanza scale) than piroxicam 20 mg. The MELISSA study, a double-blind, randomized, 28-day trial in over 9,000 patients showed that meloxicam 7.5 mg caused statistically less total GI toxicity, dyspepsia, abdominal pain, nausea and vomiting, and diarrhea than diclofenac 100 mg, despite equivalent reductions in pain on movement for each treatment. A global safety analysis of clinical trials, representing over 5,600 patients and comprising 170 and 1,100 patient-years of exposure for meloxicam 7.5 mg and 15 mg, respectively, showed that meloxicam caused less GI toxicity and fewer peptic ulcers and GI bleeds than naproxen, diclofenac, or piroxicam. The renal safety profile and incidence of liver function abnormalities with meloxicam is equivalent to other NSAIDs available for clinical use. In conclusion, relatively selective COX-2 inhibition exemplified by meloxicam may offer effective symptom relief with an improved GI tolerability profile.
 ...
PMID:Meloxicam: selective COX-2 inhibition in clinical practice. 921 16

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.
 ...
PMID:Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment. 1050 39

This article provides a systematic review of the frequency and severity of adverse gastrointestinal (GI) events among patients using meloxicam, a cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drug (NSAID). A MEDLINE search of English language articles from 1990-1998, a manual search of citations from primary trials and review articles, and a manual search of proceedings from international gastroenterology meetings were conducted. Randomized clinical trials comparing the frequency of GI adverse events for meloxicam versus non-COX-2-selective NSAIDs were selected. Specific data about the frequency of dyspepsia; perforations, ulcers, and bleeds (PUBs); and withdrawal of medication because of adverse GI events was also extracted. From a pool of 62 potentially relevant citations, 12 randomized trials were identified. All trials concerning symptomatic GI adverse events used the World Health Organization's Adverse Reaction Terminology List (WHO-ARTL) to code adverse events. Patients using meloxicam had fewer GI adverse events compared with non-COX-2-selective NSAIDs (odds ratio = 0.64; 95% confidence interval [CI], 0.59-0.69). Patients using meloxicam experienced less dyspepsia (odds ratio = 0.73; 95% CI, 0.64-0.84), fewer PUBs (odds ratio = 0.52; 95% CI, 0.28-0.96), and less frequent discontinuation of NSAID because of adverse GI events (odds ratio = 0.59; 95% CI, 0.52-0.67) compared with non-COX-2 selective NSAIDs. Meloxicam, a COX-2-selective NSAID, appears to cause fewer adverse GI events than standard, non-COX-2-selective NSAIDs. However, the generalizability of these data may be limited by the low dose of meloxicam used in most trials and the use of the WHO-ARTL to code adverse events.
 ...
PMID:Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. 1062 93

Sufficient therapy of pain is essential for the treatment of tumor patients. World Health Organisation (WHO)-guidelines recommend a combination of opioids with non-opioid-analgesics (NOA) for patients with medium to strong pain. Cancer pain is often a combination of pain caused by the tumor itself, tumor associated and pain caused by therapy. Various substances act by different mechanisms and therefore combinations may demonstrate superior effects. Opioids ("central analgesics") inhibit neuronal transduction within the spinal cord, enhance inhibiting function of midbrain nuclei on ascending pain transduction and influence pain perception via modulation of the limbic system. NOAs ("peripheral analgesics") inhibit cyclooxygenase hindering activation of the peripheral nociceptor-system. There are 2 different classes of NOAs: 1) non-acidic, antipyretic analgesics like pyrazolones (metamizol) and anilin-derivates (paracetamol) and 2) non-steroidal antirheumatics (NSAR) like salicylates (acetylsalicylic acid), derivates of propionic acid (ibuprofen, naproxen), acetate acid (indomethacin, diclofenac), enolic acid (piroxicam, meloxicam) and anthranil acid (mefenamin). Adjuvant therapy is necessary to control common NSAR-side-effects like dyspepsia, ulcer and gastrointestinal bleeding. Due to its exceptional analgesic, antipyretic and spasmolytic properties, metamizol is an essential substance in tumor therapy. As agranulocytosis-incidence of 1:1,000,000 is low, good gastrointestinal and renal tolerance makes metamizol an excellent alternative to NSAR. There is scientific evidence that adequate combinations of non-opioids, opioids and adjuvant drugs, considering adverse side effects, were effective and safe in the treatment of cancer pain.
 ...
PMID:[Non-opioid analgesics--irreplaceable in cancer pain therapy? 1113 Jan 28

Rheumatoid arthritis and osteoarthritis are prevalent and costly conditions. A large proportion of the direct costs associated with these conditions relates to management of iatrogenic side effects. The cyclooxygenase (COX)-2-specific inhibitors lead to equivalent control of pain and disability compared with traditional NSAIDs. However, the COX-2-specific inhibitors have significant potential to reduce health-care costs, principally through the reduction of side effects. These cost savings are most likely to be realized through reductions in costs associated with dyspepsia and upper gastrointestinal ulcers and bleeding. Reduced indirect costs through improved disability scores and improved health-related quality of life are also predictable with the use of COX-2-specific inhibitors. This is accomplished without the attendant increase in risk to the gastrointestinal tract associated with traditional NSAIDs.
 ...
PMID:The economic implications of cyclooxygenase-2-specific inhibitors. 1117 51

Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side-effects including complications such as bleeding and perforation, which occur in 1-2% of patients after 6-12 months of therapy. A high level of non-prescription non-steroidal anti-inflammatory drug use is observed among those presenting complications. More common side-effects are symptomatic gastro-duodenal ulcers (annual incidence of 4-8%) and dyspepsia (25-50%). Low-dose aspirin use is also associated with an increased risk of upper gastrointestinal bleeding, but the increase is about 3 times lower than that found with common non-steroidal anti-inflammatory drugs. Recent studies suggest that the risk of bleeding in patients taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to that in patients taking non-selective non-steroidal anti-inflammatory drugs. Epidemiological studies have also shown that nitric oxide donors and antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in non-steroidal anti-inflammatory drug and low-dose aspirin users.
 ...
PMID:Cyclo-oxygenase-1/cyclo-oxygenase-2 non selective non-steroidal anti-inflammatory drugs: epidemiology of gastrointestinal events. 1182 60

Nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin, are among the most frequently prescribed medications worldwide. The main factor limiting use of NSAIDs is concern about their gastrointestinal (GI) side effects. The purpose of this article is to review the incidence, pathophysiology, and risk factors of GI side effects associated with NSAID therapy. Upper GI symptoms, such as dyspepsia, occur in 15% to 60% of NSAID users, twice as often as in individuals not taking NSAIDs. The prevalence of gastric or duodenal ulcers in patients taking NSAIDs regularly is approximately 15% to 30%. The annual incidence of NSAID-related clinical upper GI events (complicated and symptomatic ulcers) is approximately 2.5% to 4.5%, with the annual incidence of serious complications (severe bleeding, perforation, and obstruction) about 1% to 1.5%. A history of ulcer or GI complications, advanced age, concomitant anticoagulation therapy or corticosteroid use, and high-dose or multiple NSAID therapy are associated with an increased risk of GI events during NSAID therapy. The cyclooxygenase (COX)-2 specific inhibitors (coxibs) have been developed in order to improve the GI safety and tolerability profile of therapy with NSAIDs. In numerous clinical trials, coxibs have been shown to have efficacy similar to that of nonselective NSAIDs, but are associated with significantly fewer endoscopic ulcers. In addition, 2 large outcome trials indicated that coxibs can also reduce the incidence of clinically important GI events.
 ...
PMID:The gastrointestinal effects of nonselective NSAIDs and COX-2-selective inhibitors. 1252 71

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.
 ...
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

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.
 ...
PMID:Prevention of nonsteroidal anti-inflammatory drug-associated gastrointestinal symptoms and ulcer complications. 1547 55


1 2 3 Next >>