Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392326 (discomfort)
 22,423 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and abnormal defecation. Polycarbophil calcium, a water-absorbing polymer, is expected to improve stool consistency. Polycarbophil calcium decalcified under the acidic condition and then absorbed 70 times its weight of water under the neutral condition. In in situ experiments using rat jejunum and colon, polycarbophil decreased water absorption by the intestine without affecting water secretion. Polycarbophil inhibited prostaglandin E2-, 5-hydroxy-L-tryptophan- and castor oil-induced diarrhea in mice or rats. Polycarbophil calcium also inhibited sennoside-induced diarrhea in dogs. Polycarbophil increased the weight of feces in naive or low-fiber diet feeding rats. In naive dogs, polycarbophil calcium increased stool frequency, stool weight and moisture. Polycarbophil was not absorbed from the gastrointestine, not metabolized and eliminated into feces in rats and dogs. Polycarbophil calcium did not affect the absorption of coadministered drugs in dogs. In the dose-finding clinical study for IBS, polycarbophil calcium was effective both in diarrhea and constipation. In the Phase III study, polycarbophil calcium was superior to trimebutine maleate in efficacy and equal in safety. Emesis/vomiting and thirst were observed, but episodes of diarrhea or constipation by excessive action were few. Polycarbophil calcium seems promising as an anti-IBS agent.
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PMID:[Physicochemical and pharmacological characteristic and clinical efficacy of an anti-irritable bowel syndrome agent, polycarbophil calcium (Polyful)]. 1191 21

Several features of the irritable bowel syndrome (IBS) suggest involvement of the emotional limbic system in the brain. Abnormalities which upregulate afferent (sensory) signal intensity anywhere in this system, from the gastrointestinal tract to the brain, could induce hypersensitivity, leading to the pain and discomfort that characterise IBS and other functional disorders. Functional gastrointestinal disorders are likely to be heterogeneous given the complexity of the afferent system, and a number of different perturbations are possible. Intestinal hypersensitivity to pain and discomfort and associated reflex alterations in motility might explain the symptoms of functional bowel diseases.
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PMID:Role of the brain and sensory pathways in gastrointestinal sensory disorders in humans. 1207 61

Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.
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PMID:Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome. 1207 70

Irritable bowel syndrome (IBS) comprises a major proportion of gastrointestinal and primary care practice worldwide. The past several years have seen the rapid evolution of a new and comprehensive model of IBS based on alterations in brain-gut interactions. Alterations in the bidirectional communication between the enteric nervous system and the central nervous system are implicated in the pathogenesis of IBS. 5-Hydroxytryptamine (5-HT; serotonin), a major neurotransmitter in the gastrointestinal tract, and its receptors 5-HT3 and 5-HT4 are involved in the control of gastrointestinal function. A number of abnormal motor and sensory patterns have been reported in patients with IBS. However, it is not known whether these abnormalities are related to symptoms or have a role in establishing a diagnosis of functional gastrointestinal disorders. Visceral hyperalgesia in IBS patients can be secondary to altered receptor sensitivity at the viscus itself and altered central modulation of sensation involving psychological influences in the interpretation of these sensations. The development of diagnostic criteria for IBS helps to avoid unnecessary and costly investigations. A detailed history allows us to diagnose IBS and search for another cause if warning symptoms are present. The Rome criteria are presently used to define IBS and are currently the most widely applied criteria used in clinical diagnosis and research purposes. Abdominal pain or discomfort associated with chronic altered bowel habits are the mainstay in diagnosis, while the supportive criteria may be used to further classify IBS patients into diarrhea-predominant or constipation-predominant subgroups. Minimal diagnostic tests have been advocated in the initial diagnostic approach to patients with suspected IBS, depending on the predominant symptom. The therapeutic goals in IBS must focus on the overall well-being of the patient, including abdominal symptoms and the accompanying nonbowel symptoms and affective disorders. It is important to establish an effective physician-patient relationship and to reassure the patient once the diagnosis of IBS is made. Dietary modification may be of value in some patients with IBS. Dietary fiber is frequently recommended for patients with constipation-predominant IBS. Two novel serotonin agonists are currently under development for constipated IBS patients, tegaserod and prucalopride. Antidiarrheal agents, including loperamide and diphenoxylate, may help patients with diarrhea-predominant IBS. 5-HT3 receptor antagonists may play a role in the management of such patients in the future. Psychological treatment and antidepressants should be considered when IBS symptoms are severe or refractory or associated with psychological distress and impaired quality of life.
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PMID:Irritable bowel syndrome: update on pathogenesis and management. 1211 90

Tegaserod is a selective partial agonist acting on serotonergic type 4 receptors (5-HT(4)). Pharmacodynamic studies indicate that tegaserod is able to stimulate gut propulsion and secretion with a net prokinetic effect. In contrast to other 5-HT(4) agonists endowed with a complex pharmacological profile, tegaserod has a reliable prokinetic activity in the colon. Clinical trials show that tegaserod is effective and safe in the treatment of patients with irritable bowel syndrome. In particular, tegaserod relieves symptoms of abdominal pain, discomfort, abdominal bloating and constipation.
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PMID:Tegaserod: a new 5-HT(4) agonist in the treatment of irritable bowel syndrome. 1215 Jun 98

Widespread symptoms associated with the irritable bowel syndrome (IBS) are abnormal defecation and abdominal pain, both of which can be exacerbated by psychogenic stress. Disordered defecation may present as diarrhea or constipation. A subgroup of IBS patients alternate from one to the other over time. Urgency to stool often accompanies the diarrheal-state, and patients with the constipation-predominant form of IBS report straining and the feeling of incomplete evacuation. Basic scientific research aims for improved understanding of the physiology and pathophysiology of the digestive systems from which the arrays of IBS symptoms emerge. The key systems for the defecation-related symptoms are the intestinal secretory glands, the musculature, and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts of the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication, and the brain-gut axis.
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PMID:Neuropathophysiology of irritable bowel syndrome. 1218 33

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

Tegaserod, a selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT(4) receptor partial agonist, is indicated in patients with irritable bowel syndrome (IBS) who identify abdominal pain or discomfort and constipation as their predominant symptoms. Tegaserod at dosages of 1 to 12 mg/day exerts pharmacodynamic actions in the upper and the lower gastrointestinal tract, accelerating small bowel and colonic transit in patients with IBS. Tegaserod is rapidly absorbed following oral administration; peak plasma concentrations (C(max)) are reached after approximately 1 hour. Absolute bioavailability is about 10% under fasted conditions. Food reduces the bioavailability of tegaserod by 40 to 65% and the C(max) by 20 to 40%. Systemic exposure to tegaserod is not significantly altered at neutral gastric pH compared with the fasted state (pH 2). Tegaserod is approximately 98% bound to plasma proteins, primarily to alpha(1)-acid glycoprotein, and has a volume of distribution at steady-state of 368 +/- 223L. Tegaserod is metabolised mainly via two pathways. The first is a presystemic acid-catalysed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide (M 29.0). This metabolite has negligible affinity for 5-HT(4) receptors and is devoid of promotile activity. The second is direct glucuronidation which leads to generation of three isomeric N-glucuronides. The plasma clearance of tegaserod is 77 +/- 15 L/h, with an estimated terminal half-life of 11 +/- 5 hours following intravenous administration. Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in faeces, with the remainder excreted in urine, primarily as M 29.0. The pharmacokinetics of tegaserod are dose-proportional over the range 2 to 12mg given twice daily for 5 days, with no relevant accumulation. The pharmacokinetics of tegaserod in patients with IBS are comparable to those in healthy individuals, and similar between men and women. No dosage adjustment is required in elderly patients or those with mild to moderate hepatic or renal impairment. Tegaserod should not be used in patients with severe hepatic or renal impairment. No clinically relevant drug-drug interactions with tegaserod have been identified. In vivo drug-drug interaction studies with theophylline [a cytochrome P450 (CYP) 1A2 prototype substrate], dextromethorphan (a CYP2D6 prototype substrate), digoxin, warfarin and oral contraceptives have indicated no clinically relevant interactions and no requirement for dosage adjustment.
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PMID:Clinical pharmacokinetics of tegaserod, a serotonin 5-HT(4) receptor partial agonist with promotile activity. 1240 41

The 5HT3 receptor antagonist alosetron has been tested in several trials on irritable bowel syndrome (IBS) patients. The aim of the present meta-analysis was to determine its effect on adequate relief of pain or global improvement of symptoms in IBS patients. Six large, multicentre, randomized, placebo-controlled trials fulfilled pre-set criteria for high quality and were included in the meta-analysis; 1762 patients were randomized to alosetron treatment and 1356 to placebo. Seventy-five per cent of the patients experienced diarrhoea-predominant IBS and 93% were females. The pooled odds ratio for adequate relief of pain or global symptoms improvement was 1.81 [95% confidence interval (CI) 1.57-2.10). The average number of patients needed to treat with alosetron for one patient to achieve improvement over placebo treatment was seven (95% CI 5.74-9.43). The present analysis shows that alosetron 1 mg b.i.d. positively impacts global symptoms, and pain and discomfort in non-constipated IBS female patients. One in four patients treated with alosetron may develop constipation. The efficacy of alosetron is unclear in male patients.
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PMID:Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials. 1258 72

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


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