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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Anticholinergics and prokinetics are mainstays of therapy for Irritable Bowel Syndrome (IBS) patients despite their limited efficacy and troublesome side-effect profile. The clinical limitations of these drugs are a result of their relative broad and nonspecific pharmacologic interaction with various receptors. Recent advances in gut physiology have led to the identification of various receptor targets that may play a pivotal role in the pathogenesis of IBS. Medicinal chemists searching for safe and effective IBS therapies are now developing compounds targeting many of these specific receptors. The latest generation of anticholinergics, such as zamifenacin, darifenacin, and YM-905, provide selective antagonism of the muscarinic type-3 receptor. Tegaserod, a selective 5-HT4 partial agonist, tested in multiple clinical trials, is effective in reducing the symptoms of abdominal pain, bloating, and constipation. Ezlopitant and nepadudant, selective antagonists for neurokinin receptors type 1 and type 2, respectively, show promise in reducing gut motility and pain. Loperamide, a mu (mu) opioid receptor agonist, is safe and effective for IBS patients with diarrhea (IBS-D) as the predominant bowel syndrome. Fedotozine, a kappa (kappa) opioid receptor agonist, has been tried as a visccral analgesic in various clinical trials with conflicting results. Alosetron, a 5-HT3 receptor antagonist, has demonstrated efficacy in IBS-D patients but incidents of ischemic colitis seen in post-marketing follow-up resulted its removal from the market. Compounds that target cholecystokinin. A, N-methyl-D-aspartate, alpha 2-adrenergic, and corticotropin-releasing factor receptors are also examined in this review.
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PMID:Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. 1218 41

The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well- tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT4-receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT3-receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge.
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PMID:Evaluation of drug treatment in irritable bowel syndrome. 1296 80

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.
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PMID:Spectrum of use and tolerability of 5-HT3 receptor antagonists. 1551 6

Irritable bowel syndrome (IBS) is one of the most common 'functional' gastrointestinal disorders accounting for 3% of all primary care consultations, with a strong female predominance. Although most of the literature comes from Western industrialized societies, when it has been looked for, this disorder appears to be equally common in the Third World. It is characterized by chronic abdominal pain or discomfort associated with disordered bowel habit and visceral hypersensitivity. Anxiety and somatization are more common in IBS than in the general population and may encourage consultation; however, they correlate poorly with symptoms. Bacterial gastroenteritis may be followed by the development of IBS in 5-10% of patients, depending on the severity of initial illness and prior anxiety or depression. The Rome criteria allow reliable diagnosis provided that there are no 'alarm' features which mandate further investigation. Microscopic colitis and bile salt malabsorption can easily be mistaken for IBS, as can chronic infestations or infections which should be considered, while recognizing that these are extremely uncommon in westernized societies. Some patients respond to exclusion diets as lactose and wheat intolerance are common. Others with prominent anxiety and/or depression respond to psychotherapy or antidepressants. Diarrhoeal symptoms respond to loperamide and 5HT3 receptor antagonists, while constipation responds to 5HT4 agonists. Antispasmodics may have limited benefit in treating pain. Low-dose tricyclic antidepressants are also helpful in alleviating pain and anxiety, even in those without obvious psychiatric disorders. If diagnostic criteria are met, then once diagnosed, new diagnoses rarely appear.
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PMID:Irritable bowel syndrome. 1576 61

In a literature search 16 clinical trials investigating 180-200 mg enteric-coated peppermint oil (PO) in irritable bowel syndrome (IBS) or recurrent abdominal pain in children (1 study) with 651 patients enrolled were identified. Nine out of 16 studies were randomized double blind cross over trials with (n = 5) or without (n = 4) run in and/or wash out periods, five had a randomized double blind parallel group design and two were open labeled studies. Placebo served in 12 and anticholinergics in three studies as comparator. Eight out of 12 placebo controlled studies show statistically significant effects in favor of PO. Average response rates in terms of "overall success" are 58% (range 39-79%) for PO and 29% (range 10-52%) for placebo. The three studies versus smooth muscle relaxants did not show differences between treatments hinting for equivalence of treatments. Adverse events reported were generally mild and transient, but very specific. PO caused the typical GI effects like heartburn and anal/perianal burning or discomfort sensations, whereas the anticholinergics caused dry mouth and blurred vision. Anticholinergics and 5HT3/4-ant/agonists do not offer superior improvement rates, placebo responses cover the range as in PO trials. Taking into account the currently available drug treatments for IBS PO (1-2 capsules t.i.d. over 24 weeks) may be the drug of first choice in IBS patients with non-serious constipation or diarrhea to alleviate general symptoms and to improve quality of life.
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PMID:Peppermint oil in irritable bowel syndrome. 1612 21

In the gut, serotonin (5-hydroxytryptamine: 5-HT) exerts a variety of effects on intrinsic enteric neurons, extrinsic afferents, enterocytes and smooth muscle cells, which are related to the expression of multiple 5-HT receptor types and subtypes regulating motility, vascular tone, secretion and perception. Agonists and antagonists at 5-HT receptors have gained access to the market for the two major variants of the irritable bowel syndrome (IBS), a functional disorder characterized by abdominal pain associated with diarrhea and/or constipation in the absence of any organic abnormality. Indeed, the 5-HT3 receptor antagonist alosetron is available in the US market for the treatment of women with severe, diarrhea-predominant IBS (D-IBS) refractory to conventional therapy, whereas tegaserod, a partial 5-HT4 receptor agonist, has been approved by the FDA and other regulatory agencies for the treatment of women with constipation-predominant IBS (C-IBS) or functional constipation. This review is mainly intended to discuss the role of non-neuronal (paracrine) and neuronal 5-HT in the pathophysiology of functional gastrointestinal disorders (FGIDs), such as IBS and functional dyspepsia, and the mechanisms through which drugs acting on 5-HT receptors regulate visceral motility, perception and secretion in these two conditions.
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PMID:Drugs acting on serotonin receptors for the treatment of functional GI disorders. 1669 64

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal (GI) disorder, but its pathophysiology remains unknown. 5-hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter involved in the brain-gut connection. Alosetron, a 5-HT3 receptor antagonist, has been demonstrated in randomized, placebo-controlled trials (RCT) to be effective in diarrhea-predominant IBS(IBS-D). Constipation is the most common adverse event. Alosetron improved abdominal pain and discomfort and stool consistency in both female and male patients, but it did not improve other symptoms (sense of urgency, stool frequency and bloating) in male patients. Although less is known about the gender differences in therapeutic benefit, a new 5-HT3 antagonist, cilansetron, has demonstrated effectiveness in male and female IBS-D patients and is currently under clinical trials.
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PMID:[Antagonists of the type 3 serotonin receptor (5 -HT3) in IBS]. 1689 18

Serotonin (5-HT) plays a critical role in the regulation of gastrointestinal motility, secretion and sensation. Serotonin is secreted by enterochromaffin (EC) cells and acts on receptors located on smooth muscles, enterocytes and nerves (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT7). Enterocytes express the serotonin reuptake transporter (SERT), which terminate the action of 5-HT. There are lines of evidence that functional gastrointestinal disorders, as irritable bowel syndrome (IBS), are associated with defective enteric serotonergic signaling. Plasma level and mucosal cells containing EC are increased in diarrhea predominant IBS. Serotonin reuptake transporter expression in colonic mucosa is significantly reduced in IBS. Moreover, 5-HT receptor agonists and antagonists seem to be effective in the treatment of symptoms of IBS. 5-HT3 receptor antagonists--alosetrone, granisetrone, ondansetrone--modulate visceral sensitivity and slow intestinal transit. They have proved to be effective in diarrhea predominant IBS. 5-HT4 agonists--tegaserode, prucalopride--relieve abdominal pain and bloating and improve intestinal transit in constipation predominant IBS. 5-HT4 antagonist--piboserode--is being investigated for a diarrhea predominant IBS.
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PMID:[Role of serotonin in the pathophysiology of the irritable bowel syndrome]. 1817 58

In irritable bowel syndrome, the main objectives of the treatment are the relief of abdominal pain then the improvement of bowel disturbances. Spasmolytic agents, or clays remain routinely the first line pharmacological options. The efficacy of dietary recommendations is not validated in most of the cases while dietary fibers, mainly insoluble fibers, may even worsen abdominal discomfort. In C-IBS, osmotic laxatives or macrogol are effective to improve colonic transit while loperamide and also colestyramine can be prescribed to reduce the number of stools of D-IBS patients. When the first line treatment fails to improve symptoms, antidepressants (tricyclic rather than SSRs) can be prescribed at lower doses than that recommended for depression. In meta-analysis, the odds ratio for pain relief varies from 2 to 4 and strongly depends on the patient's compliance to the treatment. Probiotics, pregabalin and even antibiotics (i.e neomycin, metronidazole or rifaximin), are possible new therapeutic options. Few clinical trials suggest that ramosetron (a new 5HT3 antagonist), octreotide, melatonin, or lidocain could be also discussed in the future. A non pharmacological therapeutic approach has to be considered, particularly in patients with severe symptoms, in combination with pharmacological treatment.
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PMID:[Irritable bowel syndrome: dietary and pharmacological therapeutic options]. 1930 41


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