Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastroesophageal reflux disease (GERD), functional dyspepsia and irritable bowel syndrome (IBS) often coexist and may share a common pathophysiological mechanism. An association between GERD and asthma has been reported, and IBS patients have been shown to have an excess prevalence of bronchial hyperresponsiveness. Patients with overlapping IBS and dyspepsia have delayed gastric emptying rates as well as increased visceral hypersensitivity in both the colon and the stomach. Postinfectious occurrence of concomitant dyspepsia and IBS has also been reported, as has a familial association in functional gastrointestinal disorders. Although GERD, dyspepsia and IBS are highly prevalent conditions, overlapping symptoms should be not be attributed to their high prevalence but to a possible common disease process in a subset of patients.
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PMID:Overlapping abdominal symptoms: why do GERD and IBS often coexist? 1698 65

As knowledge of the human genome grows, there will be a direct impact on the management of specific diseases. Within gastroenterology and hepatology, there has been a change in the understanding of how variations or mutations in genes involved in drug metabolism or disease pathophysiology affect response to therapy. This review discusses the application of clinical pharmacogenetics to the following diseases and disorders: inflammatory bowel disease, Helicobacter pylori infections, gastroesophageal reflux disease, irritable bowel syndrome, functional dyspepsia, liver transplantation and colon cancer. Although only a few genotyping tests are regularly used in clinical practice, it is anticipated that studies will propel the routine use of many of the tests described in this review, in the future.
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PMID:Clinical application of pharmacogenetics in gastrointestinal diseases. 1702 Apr 13

Evidence points to a significant overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). In this study, we evaluate this overlap by conducting a systematic review of the literature. Six electronic databases from 1966 through January 2005 were screened by multiple search terms to identify all epidmiological evidence linking IBS and GERD. In addition, AGA meeting abstracts for 2003 and 2004 were also screened. All studies were validated by the authors and data extracted according to predefined criteria. As a separate search strategy, studies evaluating the prevalence of IBS and GERD in the general population were sought. These articles were obtained to compare the prevalence of IBS and GERD in the community to the degree of overlap. The search identified 997 original titles with 15 publications that fulfilled our eligibility criteria. Among the 15 studies, 7 determined the GERD maximum mean prevalence in patients already diagnosed with IBS to be 39.3% and the weighted mean 30.3%. The other 7 studies examined the prevalence of IBS in patients already diagnosed with GERD. The maximum mean prevalence of IBS in subjects with known GERD was 48.8% and the weighted mean 60.5%. Based on the prevalence of IBS (12.1%) and GERD (19.4%) in the community, the rate of IBS in the non-GERD community was calculated to be only 5.1%. There is a strong overlap between GERD and IBS that exceeds the individual presence of each condition. In the absence of GERD, IBS is relatively uncommon.
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PMID:Studying the overlap between IBS and GERD: a systematic review of the literature. 1708 Feb 46

Dexloxiglumide is a potent and selective cholecystokinin type 1 (CCK1) receptor antagonist currently under development in a variety of diseases affecting the gastrointestinal tract such as gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), functional dyspepsia, constipation and gastric emptying disorders. In female patients with constipation-predominant IBS, clinical efficacy has been demonstrated following administration of dexloxiglumide 200 mg three times daily. Dexloxiglumide is rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect. Following multiple-dose administration of 200 mg three times daily, the accumulation is predictable, indicating time-independent pharmacokinetics. In addition, dexloxiglumide pharmacokinetics are dose-independent after both single and repeated oral three-times-daily doses in the dose range 100-400 mg. Dexloxiglumide absorption window extends from the jejunum to the colon and the drug is a substrate and a weak inhibitor of P-glycoprotein and multidrug resistance protein 1. Plasma protein binding of dexloxiglumide is 94-98% and the drug has a moderate to low volume of distribution in humans. Systemic clearance of dexloxiglumide is moderate and cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxi-glumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive. In addition, the drug is a single isomer chiral drug (eutomer) that does not undergo chiral inversion into its pharmacologically inactive enantiomer (distomer). After oral administration of (14)C-dexloxiglumide, radioactivity is mainly excreted in bile and in faeces (74% of dose) with much lower excretion in urine (20% of dose). Renal excretion of unchanged dexloxiglumide is low (7% of dose in urine and faeces, 1% of dose in urine) and is dose-independent in the dose range 100-400 mg. As the kidney is a minor contributor to the elimination of dexloxiglumide and/or its metabolites in humans, the pharmacokinetics of the drug should not be affected in patients with renal insufficiency. The pharmacokinetics of dexloxiglumide are also not affected by age, sex and administration with a high-fat breakfast. Mild and moderate liver impairment do not affect the pharmacokinetics of dexloxiglumide but severe liver impairment causes increases in systemic exposure to dexloxiglumide and O-demethyl dexloxiglumide. Thus, the drug should be prescribed with caution in patients with severe hepatic impairment even though no dose adjustment is warranted. The results of different drug interaction studies have indicated that no clinically relevant metabolic and concomitant drug-drug interactions are expected during the clinical use of dexloxiglumide.
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PMID:Pharmacokinetic profile of dexloxiglumide. 1711 94

Stress has been defined as an acute threat to the homeostasis of the organism. The mucosal lining of the gastrointestinal tract, a single layer of epithelial cells held together by tight junctions, provides a barrier between the external environment and the body's internal milieu. Any mechanism that breaches the tight junction exposes the body to foreign material be it protein, microorganisms or toxins. Stresses include physiological (exercise), psychological, disease-related or drug-induced factors. Stress associated gastrointestinal disorders include functional dyspepsia irritable bowel syndrome (IBS), gastroesophageal reflux disease peptic ulcer disease, and inflammatory bowel disease (IBD). Some disease states disrupt gastrointestinal barrier function, e.g. infectious diarrhea, IBD, or celiac disease, whilst in others such as eczema it can be indirectly related to antigenic disruption of the barrier. Drugs, e.g. chemotherapy agents and nonsteroidal anti-inflammatory drugs, also disrupt barrier function. Malnutrition and nutritional deficiencies (zinc, folic acid, vitamin A) also predispose to mucosal damage. Assessment of gastrointestinal mucosal health has proved problematic as invasive techniques, whilst useful, provide limited data and no functional assessment. Noninvasive tests particularly breath tests do provide functional assessment and many can be used together as biomarkers to improve our ability to define a stressed mucosa. Therapeutic options include pharmacotherapies, immunomodulation or immunotherapy.
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PMID:Stressed mucosa. 1724 96

Dynogen Pharmaceuticals Inc, under license from Mitsubishi Pharma Corp, is developing pumosetrag (MKC-733, DDP-733), an orally available gastroprokinetic agent and locally acting 5-HT3 partial agonist, for the potential treatment of irritable bowel syndrome (IBS) with constipation and nocturnal gastroesophageal reflux disease (GERD). In September 2005, Dynogen commenced a phase II proof-of-concept trial of pumosetrag in IBS with constipation; positive results were reported in February 2007 and a phase IIb trial was to start in the fourth quarter of 2007. In September 2006, the company had initiated a phase Ib trial in nocturnal GERD.
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PMID:Drug evaluation: Pumosetrag for the treatment of irritable bowel syndrome and gastroesophageal reflux disease. 1752 Aug 71

Gastroesophageal reflux disease (GERD) is currently defined as a condition that develops when the reflux of stomach contents causes recurrent symptoms and/or complications. The clinical presentation of GERD has been recognized to be much broader than before, when the typical symptoms of heartburn and acid regurgitation were considered as the main clinical presentation. However, now it is recognized that GERD can present with various other mainly extraesophageal symptoms, abdominal pain, and even sleep disturbance. Moreover, there is an important overlap with functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome. The morphologic spectrum of esophageal involvement in GERD encompasses erosive (erosive reflux disease ), Barrett's esophagus (BE), and nonerosive reflux disease (NERD). However, there is still no consensus on whether GERD represents one disease that can progress from NERD to ERD and BE, or whether it is a spectrum of different conditions with its own clinical, pathophysiologic, and endoscopic characteristics. Recently published data suggest that mild erosive esophagitis behaves in a way similar to NERD and that there is considerable movement between these categories. But follow-up data also show that after 2 years, some patients with NERD or GERD Los Angeles A or B went on to develop severe GERD or even BE. A practical approach is to categorize patients with reflux symptoms into "functional heartburn" (ie, reflux symptoms and negative endoscopy and absent objective evidence of acid reflux into the esophagus), NERD (negative endoscopy but positive documentation of acid reflux into the esophagus), and ERD (erosions documented endoscopically). In conclusion, it appears that GERD is a disease with a spectrum of clinical and endoscopic manifestations, with characteristics that make it a continuum and not a categorical condition with separate entities. It is difficult to clearly delineate the spectrum of GERD based on the clinical, endoscopic, and pathophysiologic characteristics, but therapeutic trials and follow-up studies suggest that GERD is not composed of different conditions.
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PMID:Functional heartburn, nonerosive reflux disease, and reflux esophagitis are all distinct conditions--a debate: con. 1776 Nov 23

There is a large unmet need for effective drugs for the treatment of gastrointestinal disorders, notably irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease. The market value for an effective irritable bowel syndrome therapeutic agent is estimated at over US10 billion dollars per annum. Each of these disorders seems to have a neural component, involving the intrinsic innervation of the gastrointestinal system, its extrinsic innervation or both. The substantially improved understanding of the transmitters, receptors and ion channels of enteric neurons that now exists has led to targeted therapy. The most promising targets so far have been 5-hydroxytryptamine receptors. Other targets include opioid, cholecystokinin, tachykinin, cannabinoid, corticotropin-releasing factor and protease-activated receptors. Ion channels are also potential targets. Although current knowledge has yet to be adequately translated into effective therapies, each of the targets holds promise for the future that might be realized as new compounds with appropriate receptor specificity and pharmacodynamic profiles are developed.
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PMID:Novel therapeutic targets for enteric nervous system disorders. 1776 56

Colon specific drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Chron's disease, ulcerative colitis, irritable bowel syndrome, cancer or infections, but also for the potential it holds for the systemic delivery of proteins (e.g. insulin) and therapeutic peptides. These systems enable the protection of healthy tissues from the side effects of drugs and the drug intake of targeted cells, as well. The formulation of colon specific drug delivery systems is of great impact in the case of diseases having circadian rhythm (midnight gerd). Such circadian rhythm release drug delivery systems are designed to provide a plasma concentration--time profile, which varies according to physiological need at different times during the dosing period, i.e., mimicking the circadian rhythm and severity/manifestation of gastric acid secretion (and/or midnight gerd). In general four primary approaches have been proposed for colon targeted delivery namely pH-dependent systems, time dependent systems, colonic microflora activated systems and prodrugs.
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PMID:[Site-specific drug delivery systems. I. Colon targeted delivery]. 1801 84

Functional dyspepsia is a highly prevalent disorder that accounts for 5% of visits to primary care clinicians. It frequently coexists with other gastrointestinal tract disorders, including irritable bowel syndrome and gastroesophageal reflux disease. Symptoms of functional dyspepsia, including epigastric pain, early satiety, and postprandial nausea, are nonspecific, making its diagnosis difficult. Functional dyspepsia is a heterogeneous disorder involving a number of different pathophysiologic processes, culminating in both gastrointestinal sensory and motor dysfunction. Although functional dyspepsia does not impart any increased risks to long-term health, it significantly affects both individuals and society. The economic burden of evaluating and treating functional dyspepsia is estimated to be at least $1 billion per year, and patients with functional dyspepsia experience a markedly reduced quality of life. Using the case of Ms C, we apply an evidence-based approach to highlight current knowledge in the diagnosis, evaluation, and treatment of functional dyspepsia.
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PMID:A 32-year-old woman with chronic abdominal pain. 1816 96


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