Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT(3) receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT(4) agonists such as Prucalopride and 5-HT(4) partial agonists such as Tegaserod.
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PMID:Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease. 1762 85

Rectovaginal endometriosis is a severe variant of endometriosis. Common presenting symptoms for endometriosis include dysmenorrhoea, pelvic pain and dyspareunia. It is now recognised that there are other less traditional symptoms of endometriosis that are also relatively common. The aim of this study is to assess the relative strength of each of the potential symptoms of rectovaginal endometriosis and compare these with the laparoscopic and histological findings. In this retrospective, observational study the overall prevalence of rectovaginal endometriosis in the group was 31.4%. The presence of dyschesia gave a likelihood ratio of 1.27 (95% CI: 0.56 - 2.89) with a predictive prevalence of rectovaginal endometriosis of 37%. Apareunia and nausea or abdominal bloating were particularly strong markers for rectovaginal disease with a predictive prevalence of 87% and 89%, respectively. The classical symptoms often attributed to irritable bowel syndrome are also common in women with rectovaginal disease.
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PMID:Predicting the presence of rectovaginal endometriosis from the clinical history: a retrospective observational study. 1770 98

In an outbreak of waterborne giardiasis where 1300 subjects were diagnosed, with Giardia lamblia, 139 continued to have abdominal symptoms of whom two of three had negative stool culture and microscopy. These were considered to have a postinfectious functional gastrointestinal disorder. We investigated visceral hypersensitivity in patients with persisting abdominal symptoms after Giardia infection and assessed the effect of 5HT(3)-antagonist ondansetron. Twenty-two patients with Giardia negative stools and 19 controls were included. A subset of patients (n = 15) had both irritable bowel syndrome (IBS) and functional dyspepsia (FD). All subjects underwent a satiety test with a soup combined with three-dimensional ultrasound. Fifteen of 22 patients underwent double-blind, randomized, placebo-controlled study with the 5-HT(3) antagonist ondansetron given orally. Drinking capacity was lower in patients than in controls (P < 0.01) and gastric emptying was reduced (P < 0.05). Patients had more symptoms both fasting and postprandially (P < 0.001) compared to controls. Ondansetron had no effect on these parameters except from less nausea postprandially (P < 0.05). In conclusion, patients with Giardia-induced gastrointestinal symptoms developed both IBS and FD. They exhibited gastric hypersensitivity with lower drinking capacity and delayed gastric emptying. The 5-HT(3) antagonist ondansetron did not improve drinking capacity, gastric emptying or symptoms except nausea.
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PMID:Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron. 1797 37

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

Loperamide is an antidiarrheal medication approved for the control of diarrhea symptoms and is available without a prescription. Loperamide works by a number of different mechanisms of action that decrease peristalsis and fluid secretion, resulting in longer gastrointestinal transit time and increased absorption of fluids and electrolytes from the gastrointestinal tract. It is a phenylpiperidine derivative with a chemical structure similar to opiate receptor agonists such as diphenoxylate and haloperidol. It was designed to maintain the antidiarrheal activity of these drugs, but minimize the negative aspects associated with their effects on the opiate receptor. Because of loperamides's low oral absorption and inability to cross the blood-brain barrier, it has minimal central nervous system effects. It also has a longer duration of action than diphenoxylate. However, it has no clinically significant analgesic activity and does not decrease the pain associated with some forms of irritable bowel syndrome and diarrhea. Loperamide is metabolized by the cytochrome P450 (CYP) system and is a substrate for the CYP3A4 isoenzyme. Concurrent administration with CYP3A4 inhibitors may elevate loperamide concentrations. Common adverse reactions to loperamide include cramps and nausea. Loperamide is an effective treatment for patients with painless diarrhea and is considered to be free of abuse potential.
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PMID:Loperamide: a pharmacological review. 1819 61

The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.
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PMID:Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. 1830 13

Loperamide is an effective therapy for a variety of diarrheal syndromes, including acute, nonspecific (infectious) diarrhea; traveler's diarrhea; and chemotherapy-related and protease inhibitor?associated diarrhea. Loperamide is effective for the "gut-directed" symptom of diarrhea in patients with painless diarrhea or diarrhea-predominant irritable bowel syndrome. Loperamide and diphenoxylate are commonly used to treat diarrhea in numerous settings of inflammatory bowel disease. Loperamide has also been observed to increase anal sphincter tone, which may lead to improvement of fecal continence in patients with and without diarrhea. Loperamide is generally well tolerated at recommended nonprescription doses, with the most common side effects related to the impact on bowel motility (abdominal pain, distention, bloating, nausea, vomiting, and constipation).
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PMID:The role of loperamide in gastrointestinal disorders. 1847 66

The definition of irritable bowel syndrome (IBS) by Rome criteria was a major advancement in the nosology of the disease, but this goal was achieved by employing symptoms related to the gastrointestinal tract and by eliminating all symptoms that were nonspecific. The description of the course of the illness and response to treatment has been hampered by restrictions to the defining characteristics, abdominal pain and altered bowel habit. Other abdominal symptoms (e.g., bloating, nausea, and epigastric discomfort) and general somatic symptoms (e.g., fatigue, headache, and sleep disturbance) are not included in the Rome definition, yet are commonly reported by patients with IBS. This article addresses the following questions: Are comorbid conditions part of or distinct from the syndrome of IBS and other functional gastrointestinal disorders (FGIDs)? Are there overlapping abdominal or extra-abdominal symptoms confounding the definition of IBS? Are extra-abdominal somatic symptoms and/or syndromes part of the clinical presentation of IBS? Are "nondiagnostic" abdominal symptoms important in defining symptom burden in IBS? Is the concept of somatization related to IBS, and, if so, how? How can we better define the symptom burden in IBS and other FGIDs? In short, have we hampered the evaluation of IBS (and other FGIDs) by making the definitions too reductionist? While definite answers to the above questions are not possible at this time, this article proposes that the definitions of IBS or other FGIDs not be altered, but that in the process of evaluation of the clinical end points and/or severity of the diseases, consideration be given to the possibility of including other components of the symptom burden of these disorders.
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PMID:Multidimensionality of symptom complexes in irritable bowel syndrome and other functional gastrointestinal disorders. 1850 Dec 56

The 5-hydroxytryptamine 3 (5-HT3) receptor is expressed widely in the central and peripheral nervous systems, where it mediates or modulates a wide range of physiological processes. The receptor is targeted by drugs administered for nausea and/or emesis and irritable bowel syndrome and has been proposed as a potential drug target in various psychiatric disorders. The 5-HT3 receptor is a pentameric ligand-gated ion channel and belongs to the Cys-loop receptor family. In contrast to the immense heterogeneity characterizing other Cysloop receptors, native 5-HT3 receptors historically have been considered a much more homogenous receptor population. However, the recent discovery of additional 5-HT3 subunits and the dawning realization that central and peripheral 5-HT3 receptor populations might comprise several subtypes characterized by distinct functional properties has emphasized the complexity of human 5-HT3 receptor signaling. In this review potential implications of these findings and of the entirely new layer of interindividual diversity introduced to the 5-HT3 receptor system by genetic variations will be outlined.
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PMID:3B but which 3B and that's just one of the questions: the heterogeneity of human 5-HT3 receptors. 1859 59

Gastrointestinal symptoms are extremely common during pregnancy. Increased levels of female sex hormones cause or contribute to symptoms such as heartburn, nausea, vomiting and constipation. If these symptoms do not respond adequately to lifestyle and dietary changes, drug therapy is often warranted to improve quality of life and to prevent complications. Physicians, therefore, need to be familiar with the low-risk treatment options available. Treatment of chronic conditions such as IBD or chronic liver disease during pregnancy can be demanding. In women with IBD, maintenance of adequate disease control during pregnancy is crucial. Most IBD drugs can be used during pregnancy, but the benefits and risks of specific drugs should be discussed with the patient. Liver diseases can be coincidental or pregnancy-specific. Pregnancy-specific liver diseases include not only benign disorders such as intrahepatic cholestasis of pregnancy, but also pre-eclampsia, eclampsia and HELLP syndrome (hemolytic anemia, elevated liver enzymes and low platelet count). Accordingly, the spectrum of therapeutic measures ranges from expectant management to urgent induction of delivery. During pregnancy, lamuvidine therapy for chronic hepatitis B can be continued; however, interferon and ribavirin therapy for chronic hepatitis C is contraindicated. This Review provides an overview of the spectrum and therapy of motility disturbances that occur during pregnancy, and discusses pregnancy-specific aspects of IBD and liver diseases.
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PMID:The spectrum and treatment of gastrointestinal disorders during pregnancy. 1925 5


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