Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0232487 (abdominal discomfort)
 1,724 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tegaserod is a serotonin (5-hydroxytryptamine; 5-HT) receptor partial agonist which has been investigated for the treatment of irritable bowel syndrome (IBS). Specifically, it binds with high affinity to human 5-HT4 receptors, thereby stimulating the release of neurotransmitters and the peristaltic reflex in vitro. Small bowel transit (increased colonic filling over 6 hours) was accelerated in patients with constipation-predominant irritable bowel syndrome (IBS) receiving oral tegaserod 2mg twice daily for 1 week compared with those receiving placebo. In addition, there was a mean 20% increase of proximal colonic emptying in these patients. Oral tegaserod 2 (p < 0.05) or 6mg twice daily improved symptoms of abdominal discomfort, bloating and constipation (assessed using a Subjects' Global Assessment Scale) compared with placebo in patients with constipation-predominant IBS in a double-blind, dose-ranging study. The most frequent adverse events in patients with constipation-predominant IBS receiving oral tegaserod were transient diarrhoea and flatulence. No clinically relevant changes in blood pressure, pulse rate, QRS or QTc interval were reported with tegaserod doses of 25 to 100mg.
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PMID:Tegaserod. 1049 76

The effect of pinaverium bromide in controlling gastrointestinal symptoms in 61 patients with irritable bowel syndrome was studied, as an open trial. Individually, there was significant relief in abdominal discomfort/pain as well as in bowel symptoms in most of the patients. Abdominal pain was reduced in 49%, stool consistency improved in 74%, straining and urgency decreased in 71% and mucus decreased in 64%. Tolerance to the drug administered was good and side-effects reported were few.
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PMID:Role of pinaverium bromide in south Indian patients with irritable bowel syndrome. 1127 20

Irritable bowel syndrome (IBS) is a functional GI disorder that is associated with abdominal discomfort and altered bowel habits. It accounts for up to 28% of patients presenting to a gastroenterology practice and poses a significant personal, societal and economic burden internationally. The Manning, Rome I and Rome II criteria were developed to identify appropriate IBS patients for entry into IBS studies in a consistent manner. Refinements in the understanding of the physiology of the enteric nervous system (ENS), which controls motility, secretion and sensation, provided the basis for our comprehension of the pathophysiology of IBS. Visceral hypersensitivity and neurotransmitter imbalance currently receive the most attention as possible mechanisms of IBS. This article outlines conventional treatments and reviews the data on emerging and experimental therapies for IBS. Emerging therapies for IBS using 5-HT mediation include 5-HT(3) antagonists, such as ondasetron, granisetron and alosetron, as well as 5-HT(4) agonists such as tegaserod and prucalopride. In addition to opioid agonists (e.g. fedotozine) several other drugs that act on other ENS receptors are being studied. In spite of significant progress in IBS research, these emerging therapies require more studies before they can be utilised as clinical treatments.
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PMID:Emerging treatments for irritable bowel syndrome. 1177 29

A dense network of extrinsic and intrinsic sensory neurons supplies the gastrointestinal tract. Intrinsic sensory neurons provide the enteric nervous system with the kind of information that this brain of the gut requires for its autonomic control of digestion, whereas extrinsic afferents notify the brain about processes that are relevant to energy and fluid homeostasis and the sensation of discomfort and pain. The sensory repertoire of afferent neurons is extended by their responsiveness to mediators released from enteroendocrine and immune cells, which act like "taste buds" of the gut and serve as interface between the gastrointestinal lumen and the sensory nerve terminals in the lamina propria of the mucosa. Functional bowel disorders such as non-ulcer dyspepsia and irritable bowel syndrome are characterized by abdominal discomfort or pain in the absence of an identifiable organic cause. It is hypothesized with good reason that infection, inflammation or trauma causes sensory pathways to undergo profound phenotypic and functional alterations that outlast the acute insult. The pertinent changes involve an exaggerated sensitivity of the peripheral afferent nerve fibres as well as a distorted processing and representation of the incoming information in the brain. This concept identifies a number of receptors and ion channels that are selectively expressed by primary afferent neurons as important molecular targets at which to aim novel therapies for functional bowel disorders.
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PMID:Surveillance of the gastrointestinal mucosa by sensory neurons. 1178 55

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal discomfort or pain associated with changes in stool frequency and/or stool form. It is the most common gastrointestinal disorder in both primary care and gastroenterology clinics. IBS is associated with high health care costs, disability, work absenteeism, and significant morbidity. In this article, we review the gender differences in epidemiology, diagnostic criteria, physiology, psychological features, and responses to therapy of IBS.
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PMID:Gender differences in irritable bowel syndrome. 1207 61

The diagnosis of irritable bowel syndrome (IBS) is arbitrary, being based on criteria defined by consensus rather than specific biologic markers. IBS is merely a consortium of symptoms and as presently defined is no more a disease than dyspnea or fatigue are diseases. In this context, it is therefore not surprising that defining the nature of pain has proven elusive. It is often etiologically assumed that the origins of the pain seen in IBS patients are mechanistically distinct from those of some of the other symptoms of IBS such as diarrhea and constipation. In addition pain is assumed to be part of a continuum ranging from complete absence of any pain to varying degrees of discomfort to severe pain. Both of these assumptions should be challenged: there are no data to support the notion that discomfort and pain experienced in IBS are mediated through different pathways than symptoms such as bloating or that they are not merely the consequence of the physiological perturbations associated with altered bowel function. Similarly one can easily argue that visceral pain may actually be the cause rather than the effect of the altered gut function seen in IBS. Abdominal discomfort could then be the consequence of the latter and be only indirectly related to pain. It is likely that central (such as stress) and peripheral factors (such as intestinal infection) will produce similar symptoms but via markedly different pathways. It may be time to deconstruct IBS as a concept and to approach the clinical picture from a mechanistic rather than a phenomenological perspective, particularly if we are interested in understanding the basis of the symptoms and develop effective therapeutic modalities. Our patients deserve no less.
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PMID:The nature of pain in irritable bowel syndrome. 1218 36

The irritable bowel syndrome is one of a group of functional gastrointestinal disorders within the Rome classification system that is characterized by abdominal discomfort or pain associated with a change in stool habit. It is a multidetermined biopsychosocial disorder in which physiological, psychological, behavioral, and environmental factors may contribute to the clinical expression of the disorder. These can include: (1) early life (e.g., genetic or environmental) factors; (2) physiological factors including increased motor reactivity, visceral hypersensitivity, which may be enabled by postinfectious events, and dysregulation of brain-gut communication (e.g., altered central pain control mechanisms). In addition, psychosocial factors including psychiatric co-morbidity, major trauma (e.g., abuse history), and maladaptive coping may amplify the clinical expression of the disorder and its outcome. Currently, clinical outcome has become understood in terms of global symptom relief and health-related quality of life.
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PMID:Irritable bowel syndrome: classification and conceptualization. 1218 43

Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is present in 10% to 20% of the U.S. adult population. The syndrome is best defined as chronic abdominal discomfort with changes in stool frequency, consistency, and passage, with associated symptoms such as abdominal bloating or presence of mucus in stools. Several studies have shown that up to 70% to 90% of patients with IBS who seek treatment have psychiatric comorbidity, most notably mood and anxiety disorders. Recent studies have shown a high prevalence of IBS in psychiatric patients who seek treatment, with a prevalence of 19% in schizophrenia, 29% in major depression, and 46% in panic disorder among other disorders. Our article reviews the comorbidity of IBS in psychiatric patients and discusses implications for treatment.
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PMID:Comorbidity of irritable bowel syndrome in psychiatric patients: a review. 1252 23

The irritable bowel syndrome (IBS) is characterized by altered bowel habits and abdominal discomfort in the absence of organic disease. No markers exist for IBS, and the definition of IBS is based on the presence of specific symptoms. The Rome II criteria for defining IBS include abdominal pain or discomfort for 12 weeks or longer, which need not be continuous, over the past 12 months plus two of the following: (1) relief of discomfort with defecation; (2) association of discomfort with altered stool frequency; and (3) association of discomfort with altered stool form. Nine percent to 22% of the population report symptoms consistent with IBS. IBS is the most prevalent digestive disease, representing 12% of visits to primary care physicians and 28% of referrals to gastroenterologists.
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PMID:The irritable bowel syndrome during pregnancy. 1263 23

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.
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PMID:Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome. 1468 76


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