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)

Because treatment of irritable bowel syndrome (IBS) patients can be frustrating to the clinician and patient as well, the physician should strive to gain the patient's confidence with a concise, appropriate work-up and by offering reassurance and education that IBS is a functional disorder without significant long-term health risks. First-line treatment should be aimed at treating the most bothersome symptom. Tricyclic antidepressants are superior to placebo in reducing abdominal pain scores, as well as improving global symptom severity. Loperamide is superior to placebo in managing IBS-associated diarrhea. Whereas fiber has a role in treating constipation, its value for IBS or, specifically, in the relief of abdominal pain or diarrhea associated with IBS is controversial. Although certain antispasmodics have demonstrated superiority over placebo in managing abdominal pain, none of these agents are available in the United States. Probiotic therapy using Lactobacillus plantarum has demonstrated superiority to placebo in improving pain, regulating bowel habits, and decreasing flatulence. As studied in a recent placebo-controlled prospective study, Chinese herbal medicines significantly improved bowel symptom scores and global symptom profile, and reduced IBS-related quality of life impairment. Some of the most promising emerging therapies in IBS revolve around targeted pharmacotherapeutic modulation of serotonin receptors (ie, 5-HT3 and 5-HT4 subtypes), which are involved in sensory and motor functions of the gut. Other investigational agents that are also being explored include cholecystokinin antagonists, alpha2-adrenergic agonists (eg, clonidine), serotonin reuptake inhibitors (eg, citalopram), and neurokinin antagonists. IBS is best understood through the biopsychosocial paradigm, and therefore, its effective management requires a comprehensive multidisciplinary approach based on patient education and reassurance, enhanced by diet recommendations and lifestyle modifications, and complemented by pharmacotherapy and psychosocial intervention in more severe cases.
 ...
PMID:Irritable Bowel Syndrome. 1209 74

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.
 ...
PMID:Irritable bowel syndrome: update on pathogenesis and management. 1211 90

The efforts of clinical researchers, lay organizations and pharmaceutical companies have increased the public profile of irritable bowel syndrome and made it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical diagnosis, which is the foundation of a logical management strategy. This begins with education. Reassurance that no structural disease threatens should be tempered with the reality that symptoms are likely to recur over many years. Patients expect diet and lifestyle advice, even if this is not specific to irritable bowel syndrome. Only a few of those with irritable bowel syndrome see doctors, and even fewer see specialists. Therefore, the treating physician should ascertain the reason for the visit, the patient's fears and the presence of any comorbid illness, such as depression, that might require treatment in its own right. No drug treatment is useful for all of the symptoms of irritable bowel syndrome, and many patients require no drug at all. If used, drugs should target the predominant symptom. Alosetron, a 5-HT3 antagonist, is effective in treating women with irritable bowel syndrome who also have diarrhoea. Tegaserod, a 5-HT4 agonist, is useful for women with irritable bowel syndrome who are constipated. Most patients with irritable bowel syndrome need psychological support. Reassurance, discussion and relaxation techniques can be provided by the family doctor. Difficult psychopathology may require referral to a mental health professional, and the gastroenterologist can settle diagnostic uncertainties. In all cases, successful treatment depends on a confident diagnosis and the strength of the doctor-patient relationship.
 ...
PMID:The treatment of irritable bowel syndrome. 1218 40

In the treatment of the irritable bowel syndrome, it is important to qualify unrealistic expectations with regard to treatment, at an early stage. The therapeutic spectrum encompasses establishment of good rapport between physician and patient, modification of life style, provision of good patient information, reassurance, coping strategies, and temporal restraints on medication. Depending on the leading symptoms, the latter may range from laxatives to probiotics, anticholinergics or spasmolytics, prokinetic and anti-diarrheal agents, to 5-HT3/HT4 receptor antagonists. In individual patients with frequently recurrent or permanent pain, the use of tricyclic antidepressants may be considered. Painkillers should be reserved for patients in whom other therapeutic strategies have failed.
 ...
PMID:[Proper patient counseling, recommended nutrition, specific medication. The basics of irritable bowel syndrome therapy]. 1253 94

Despite significant advances in the recognition of etiological factors and pathological mechanisms, the pathophysiology of functional gastrointestinal disorders (FGD) is still not fully understood. Visceral hypersensitivity has been recognized as a characteristic of patients with FGD, especially in patients with irritable bowel syndrome (IBS). Visceral afferent input is modulated by a variety of mechanisms, operating between the gastrointestinal tract and the brain. Dysfunction of these regulatory mechanisms could distort gastrointestinal perceptions. Recent findings suggest that in the majority of cases of IBS the primary abnormality may be at the periphery with alterations of the motor and secretory sensory activity. Although imaging techniques indicate that there are also differences in cortical activation. Furthermore, selective serotonin reuptake inhibitors may benefit FGD. Recent pharmacological studies suggest that 5-HT3 antagonist such as alosetron and cilansetron, and 5-HT4 agonist such as legaserod and prucalopride may also have a potential use in FGD.
 ...
PMID:[Visceral hypersensitivity: a concept within our reach]. 1264 25

Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.
 ...
PMID:Tegaserod and other serotonergic agents: what is the evidence? 1277 1

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and change in defecation pattern. This review addresses the topic of possible sex (genetic, biological) and gender (experiential, perceptual) differences in individuals with and without IBS. Several observations make the topic important. First, there is a predominance of women as compared to men who seek health care services for IBS in the United States and other industrialized societies. Second, menstrual cycle-linked differences are observed in IBS symptom reports. Third, women with IBS tend to report greater problems with constipation and nongastrointestinal complaints associated with IBS. Fourth, serotonin (5-HT3) receptor antagonist and 5-HT4 partial agonist drugs appear to more effectively diminish reports of bowel pattern disruption in women with IBS as compared to men. This review examines sex and gender modulation of gastrointestinal motility and transit, visceral pain sensitivity, autonomic nervous system function, serotonin biochemistry, and differences in health care-seeking behavior for IBS.
 ...
PMID:Impact of sex and gender on irritable bowel syndrome. 1288 71

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by recurrent abdominal pain and altered bowel habits in the absence of any discernible structural, biochemical and physiological abnormalities. Although there is no specific biological marker for the diagnosis of this disorder, recently developed symptom-based criteria provide the tools necessary to make a diagnosis. The precise underlying pathophysiology of IBS remains unknown. However, disturbances in the brain-gut axis involving the central nervous system and the enteric nervous system have emerged as an underlying concept for IBS. In this regard, conventional treatment has been recognised as unsatisfactory for many patients with IBS and novel, neuroenteric modulatory compounds have been introduced for use by clinicians. Specifically, compounds interacting with the 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT3 and 5-HT4 subtype have been demonstrated of benefit in some patients for the treatment of IBS. In this leading article, we present the current data on the pharmacology, clinical trials, indications and adverse effects of alosetron, a potent and selective 5-HT3 antagonist. As a result of the recognition of serious adverse effects, the indication for alosetron has been restricted and it is now indicated only for women with severe diarrhoea-predominant IBS who have symptoms for at least 6 months and who have failed to respond to conventional therapy. Prescribing restrictions and the risk-management programme implemented as required by the US FDA is reviewed along with a summary of the studies to be performed after reintroduction of alosetron to monitor safety.
 ...
PMID:Alosetron in irritable bowel syndrome: strategies for its use in a common gastrointestinal disorder. 1293 Jan 62

Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder, affecting about 20% of the world's population. Chronic abdominal pain or discomfort relieved by defecation and associated with altered bowel habits are the mainstay in diagnosis. The pathophysiology of IBS remains unknown. This biopsychosocial disorder involves dysregulation of the nervous system, altered intestinal motility, and increased visceral sensitivity. All of these result from dysregulation of the bidirectional communication between the gut with its enteric nervous system and the brain (the brain-gut axis), modulated by various psychosocial and environmental factors (e.g. infection, inflammation). Numerous neurotransmitters are found in the brain and gut that regulate GI activities, including 5-hydroxytryptamine (5-HT, serotonin) and its 5-HT3 and 5-HT4 receptors. The current approach to IBS patients is based on a positive diagnosis of the symptom complex, exclusion of underlying organic disease, and institution of a therapeutic trial. Traditional symptomatic treatment has included antidiarrheals, laxatives and bulking agents/fiber, low-dose tricyclic antidepressants, antispasmodics for pain, and "alternative" therapies (e.g. psychotherapy, hypnotherapy). The scientific evidence supporting this therapy is limited. Novel approaches include visceral analgesics and serotonin agonists and antagonists. In patients with severe diarrhea, 5-HT3 receptor antagonists (e.g. alosetron) and selective M3-type anticholinergics are indicated, in constipation 5-HT4 agonists (e.g. tegaserod), and in pain alfa2-adrenergics (e.g. clonidine), cholecystokinin antagonists, kappa-opioid agonists (e.g. fedotozine), and neurokinin antagonists; some of these agents are still being investigated. Understanding the brain-gut axis is crucial in the development of effective therapies for IBS.
 ...
PMID:The brain-gut axis in irritable bowel syndrome--clinical aspects. 1517 82

The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.
 ...
PMID:Physiology and pathophysiology of the 5-HT3 receptor. 1551 4


<< Previous 1 2 3 4 5 6 7 8 Next >>