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 with functional dyspepsia, which involves no organic disease and no reflux, do not benefit from lansoprazole, a proton pump inhibitor. Any improvement seen is probably related to a placebo effect. Prescribing proton pump inhibitors for these patients just for their placebo effect is going to further raise health care costs. Antacids and H2 blockers are less expensive alternatives.
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PMID:Lansoprazole ineffective for functional dyspepsia. 1223 71

Dyspepsia is a common symptom. Dyspeptic symptoms may be caused by a variety of conditions such as peptic ulcer disease, gastro-oesophageal reflux, and malignancy. Most often, however, no cause is identified and dyspepsia is deemed to be functional. While symptom severity does influence frequency of consultation, dyspeptic consulters also differ from non-consulters with respect to symptom perception and anxiety. This highlights the importance of understanding the patient's agenda early in the course of evaluation. Patients over the age of 55 years or with alarm symptoms should be referred for prompt endoscopy. In the absence of other clinically apparent aetiologies, uninvestigated dyspeptics can be either tested and treated for Helicobacter pylori or empirically treated with proton pump inhibitors. Uninvestigated dyspeptics failing empiric therapy should be referred for evaluation that includes endoscopy. Further therapy with prokinetics, tricyclic antidepressants, fundal relaxants, antidepressants, or psychotherapy is guided by predominant symptoms and assessment of possible psychiatric factors.
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PMID:Evaluation and treatment of dyspepsia. 1256 47

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria. The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia. Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT(4) receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT(4) receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT(3) receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, kappa-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK(1)/NK(2)) and cholecystokinin (CCK)(1) receptors.
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PMID:New developments in the treatment of functional dyspepsia. 1267 73

Non-ulcer dyspepsia is common and is often confused with other diagnoses. It remains a condition identified by exclusion, and continues to be a challenge to manage. Currently, only a limited number of pharmacological options are available. Antacids are no more effective than placebo in treating nonulcer dyspepsia. H2-receptor antagonists appear to be superior to placebo in efficacy, but many of the studies suggesting this finding have had a suboptimal study design. Proton pump inhibitors have been shown to be superior to placebo, although questions remain as to whether the only subgroup that responds is comprised of patients with unrecognized gastroesophageal reflux disease. Studies have found that prokinetic agents are superior to placebo, but currently only a very limited number of agents within this class can be prescribed in the United States. Sparse data support the role of metoclopramide and its side effects limit its use even further. The eradication of Helicobacter pylori has a small but positive therapeutic benefit in non-ulcer dyspepsia, and can be considered in those confirmed to be infected. Sucralfate is unlikely to be effective, and misoprostol is ineffective. Bismuth alone is probably not efficacious. Tricyclic antidepressants may have a therapeutic role, but this is not firmly established and this class of medication should be reserved for resistant cases. Emerging therapies include drugs that relax the gastric fundus, such as buspirone or sumatriptan, and the new prokinetic tegaserod. Psychological therapies may play a role but studies of these therapies are limited. Therapy for non-ulcer dyspepsia remains challenging and is usually empiric; it will remain so until the mechanisms that induce symptoms of dyspepsia are better understood.
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PMID:Update on the role of drug therapy in non-ulcer dyspepsia. 1268 90

Apart from patients with peptic ulcer disease, the use of eradication therapy for Helicobacter pylori infection has been extended to patients with H pylori-positive dyspepsia and conditions at risk for gastric cancer. Standard treatments comprise a proton pump inhibitor plus two antibiotics for at least one week. The main factors leading to treatment failure are noncompliance and antibiotic resistance. Provided the patient is sufficiently informed about possible side effects, discontinuation of the newer triple therapies has become rare. The prevalence of antibiotic resistance varies considerably among different geographic regions, reflecting the habits of prescription of these antibiotics for other indications. Largely, it ranges from 1% to 15% for macrolides, and from 7% to 60% for nitroimidazoles. With nitroimidazole resistance, treatment failure occurs in only less than 50%; with macrolide resistance, by contrast, in more than 50% of the cases. Furthermore, bacterial and host-related factors (Cag A virulence factor, grade of inflammation) contribute to eradication success. In case of treatment failure, post-therapeutic resistance is frequent. Important principles for the choice of second-line treatment are: not to repeat an antibiotic with potential post-therapeutic resistance, and to ensure sufficient acid suppression.
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PMID:What constitutes failure for Helicobacter pylori eradication therapy? 1284 53

Most patients with peptic ulcer disease are currently treated with proton pump inhibitors or histamine H(2) receptor antagonists. The long-term use of these compounds has been associated with two potential problems. Firstly, proton pump inhibitors may induce enterochromaffin-like (ECL) cell hyperplasia. Secondly, ulcers may relapse despite maintenance therapy with histamine H(2) antagonists. This has been the rationale for the development of new antisecretory agents, including antagonists against gastrin and gastrin releasing peptide (GRP), as well as ligands to histamine H(3) receptors. Several potent, high affinity cholecystokinin (CCK)-2 receptor antagonists have recently been identified such as L-365260, YM-022, RP-73870, S-0509, spiroglumide and itriglumide (CR-2945). Current data suggest that they all have antisecretory and anti-ulcer effects. In addition to reducing acid production, CCK-2 receptor antagonists may possibly also accelerate gastric emptying, a combination of functions which could potentially be beneficial in patients with functional dyspepsia. Receptors for bombesin and its mammalian counterpart GRP have been localised in the brain, spinal cord and enteric nerve fibres of the gut as well as on secretory cells and smooth muscle cells of the intestinal tract. Current data clearly indicate that endogenous GRP is involved in the regulation of basal and postprandial acid secretion. However, at this stage it is not clear whether GRP agonists or GRP antagonists can be developed into useful drugs. The peptide has a wide range of biological effects and it is likely that analogues of GRP or antagonists of the peptide affect not only gastric acid secretion but also induce considerable side effects. Histamine plays a central role in the stimulation of acid secretion. After their detection in the brain, H(3) receptors have been identified in a variety of tissues including perivascular nerve terminals, enteric ganglia of the ileum and lung, and ECL cells. Despite many studies, the role of H(3) receptors in the regulation of gastric acid secretion is still unclear. Controversial data have been presented, and study results largely depend on the species and experimental models. It seems unlikely that proton pump inhibitors or H(2) receptor antagonists will be replaced in the near future by new antisecretory agents. The current shortcomings of the new compounds include mainly their reduced clinical effectiveness and pharmacological limitations. However, the development of these new antisecretory compounds provides interesting tools to assess the physiological and pharmacological role of different receptors within the gastrointestinal tract. The use of CCK-2 receptor antagonists in patients with functional dyspepsia and Zollinger-Ellison syndrome should be examined in randomised, controlled trials.
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PMID:New molecular targets for treatment of peptic ulcer disease. 1292 85

The field of acid suppression has been advanced by therapeutics of increasing specificity for inhibiting gastric acid secretion. Particularly important are proton pump inhibitors (PPIs), which inhibit the activity of the gastric acid pump (H+,K(+)-adenosine triphosphatase), the final common step in gastric acid production. Histamine2-receptor antagonists, which act at an early stage of the acid secretion pathway, are less effective and are subject to intolerance. The PPIs are weak bases that undergo accumulation in the acidic space of the secreting parietal cell and are converted in acid to the active thiophilic form, which then forms disulfide bonds with key cysteines of the gastric acid pump. Pantoprazole differs from other PPIs in terms of its reaction with cysteine 822 in the pump and with cysteine 813, a common binding site for all PPIs. Both cysteines are in the sixth transmembrane segment, which is part of the ion transport pathway. This selective binding may have an impact on the dwell time of pantoprazole versus other PPIs because it is inaccessible to reducing agents, in contrast to cysteine 813. Pantoprazole is also very stable (has a slow rate of activation) at neutral pH values compared with other PPIs and has a relatively robust plasma concentration-time curve. These agents are important in the management of duodenal ulcers, nonsteroidal antiinflammatory drug-induced ulcers, gastroesophageal reflux disease, and dyspepsia, but basic pharmacokinetic and pharmacodynamic differences among them may affect clinical utility.
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PMID:Physiology of the parietal cell and therapeutic implications. 1458 60

Eradication of Helicobacter pylori has lead to a significant decrease in the prevalence of peptic ulcer disease world-wide. Despite the fact that H. pylori eradication is the only way to cure peptic ulcer disease, a substantial number of patients still need antisecretory agents to be symptoms-free after eradication. During the past year several randomized controlled trials on H. pylori eradication in patients taking NSAIDs have been published but contradictory results have been obtained. In certain parts of the world, NSAIDs are becoming the main cause of peptic ulcer disease complications such as bleeding or perforation. Some patients with nonulcer dyspepsia do benefit from eradication of H. pylori as was shown in several studies. Long-term trials with cost/efficacy analysis are still needed to demonstrate the benefit of H. pylori eradication over acid inhibition in this group of patients. H. pylori prevalence is lower in patients with gastro-esophageal reflux disease, but according to recent systematic reviews it varies geographically. There are more data now to show that eradication of H. pylori in duodenal ulcer patients does not increase the incidence of GERD. The 'test and treat' strategy for patients with uninvestigated dyspepsia was strongly supported by both meta-analysis and the results of recent randomized controlled trials. Even in developed countries where the prevalence of H. pylori decreases, this strategy allows resolution of symptoms in a larger number of patients with dyspepsia compared to empirical treatment with proton pump inhibitors and reduces the endoscopic workload.
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PMID:Helicobacter pylori and nonmalignant diseases. 1461 16

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

Uninvestigated dyspepsia is very common, and it can be caused by peptic ulcer disease. However, just when patients should undergo expensive tests to determine the cause of their symptoms is not always clear-cut--particularly now that an OTC proton pump inhibitor (PPI) is available. Get some expert advice on what factors to consider when treating these patients.
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PMID:Treating dyspepsia: new OTC drug changes the economic picture. 1467 71


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