Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-Hydroxytryptamine (5-HT) is a major transmitter molecule within the gastrointestinal tract. It is contained in enterochromaffin (EC) cells, which form part of the epithelial lining of the gut and in enteric neurones in the submucosal and myenteric plexuses. 5-HT is present in murine mucosal mast cells in the lamina propria and some studies have suggested that human mast cells may also contain 5-HT especially in conditions associated with mastocytosis. The strategic positioning of the enteric and extrinsic sensory innervation in close proximity to these sources of 5-HT, in conjunction with their demonstrated sensitivity to this mediator, suggests the involvement of 5-HT in the transduction of visceral stimuli and reflex responses affecting motor and secretory function. Under physiological conditions, the release of 5-HT from these storage sites may result in the orchestration of reflexes responsible for transit of material along the bowel at a rate that is appropriate for digestion and absorption of nutrients. However, in the pathophysiological state, 5-HT acting together with other inflammatory mediators may cause inappropriate intestinal secretomotor activity and/or initiate sensations such as nausea or discomfort/pain. Current evidence suggests that the bioavailability of 5-HT within the gut wall is altered in a number of post-inflammatory models of gut dysfunction with increased numbers of EC cells and mast cells with increased 5-HT content in proximity to sensory nerve endings, and decreased serotonin reuptake mechanisms. Changes may also occur in the sensory innervation or pathways within the central nervous system. These processes may contribute to pain mechanisms in the irritable bowel syndrome, in which visceral hypersensitivity is a predominant feature and may also contribute to motor dysfunction leading to altered bowel habit.
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PMID:5-HT system in the gut: roles in the regulation of visceral sensitivity and motor functions. 1892 45

Lubiprostone, a locally acting highly selective type-2 chloride channel activator, has been US FDA approved since January 2006 for the treatment of adults with chronic idiopathic constipation and FDA approved since April 2008 for the treatment of woman aged 18 years or older suffering from irritable bowel syndrome (IBS) with constipation. Through activation of the type-2 chloride channels located on the luminal side of intestinal epithelial cells, it promotes fluid secretion, increasing the liquid content of stool and accelerating small bowel as well as colonic transit. Lubiprostone has demonstrated efficacy with respect to increasing weekly spontaneous bowel movements and improving stool consistency, straining and constipation severity, both in short- and long-term studies. It has also demonstrated efficacy in the treatment of IBS with constipation, with beneficial effects on global symptoms, abdominal pain, constipation-related symptoms and overall quality of life. There is no evidence of a rebound in constipation or IBS symptoms following cessation of lubiprostone. In general, lubiprostone is well tolerated, with the most common side effects including nausea, headache and diarrhea.
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PMID:Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation. 1907 97

Chronic constipation and irritable bowel syndrome are heterogeneous disorders characterized by altered bowel habits, abdominal discomfort and/or difficult defecation. These conditions have a significant impact on patients' quality of life, as well as on the US economy, both in terms of healthcare costs and lost productivity. Treatment typically begins with lifestyle changes, increased fiber intake and osmotic and stimulant laxative intake. However, treatments for constipation vary in terms of their efficacy and safety. Furthermore, surveys of physicians and patients have revealed a strong desire for improved therapeutic options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective and stimulates type 2 chloride channels, resulting in increased chloride, sodium and water secretion into the lumen. The increased fluid secretion causes luminal distension, secondary peristalsis and laxation. Randomized Phase III trials have shown that lubiprostone is efficacious in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. The US FDA has approved lubiprostone at a dose of 24 microg twice daily for the treatment of chronic idiopathic constipation in adults, and at a dose of 8 microg twice daily for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea and headaches are the most commonly reported side effects. In long-term studies, lubiprostone appears to be safe.
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PMID:Lubiprostone for constipation and irritable bowel syndrome with constipation. 1909 Jul 33

Irritable bowel syndrome (IBS) is a chronic, highly prevalent gastrointestinal motility disorder characterized by abdominal discomfort/pain associated with altered bowel habits such as diarrhea or constipation or both. Current therapy for the constipation-predominant form (IBS-C) comprises fiber or osmotic or stimulant laxatives. However, these may exacerbate the condition or cause electrolyte disturbances. Lubiprostone is a novel selective chloride channel-2 activator that increases fluid secretion in the intestinal apical cell membrane, increasing gut motility and frequency of stool passage, and alleviating abdominal discomfort/pain. Lubiprostone has very low systemic bioavailability and cannot be quantitated in blood, but its active metabolite, M3, has been pharmacokinetically profiled. Lubiprostone reaches peak plasma concentrations within approximately 1 h and has a half-life of 0.9-1.4 h. Despite this short half-life, lubiprostone can be administered orally twice daily. Its efficacy in IBS-C has been demonstrated in two phase III studies; spontaneous bowel movement frequency increased and stool consistency improved, whereas straining, bloating and severity of constipation decreased. The beneficial effects continued for up to 4 weeks after cessation of lubiprostone. Lubiprostone was well tolerated in the long-term, with nausea and diarrhea being the commonest adverse events. Further studies are ongoing in opioid-induced bowel dysfunction.
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PMID:Lubiprostone--a novel treatment for irritable bowel syndrome with constipation. 1913 19

Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. The FDA has approved lubiprostone for the treatment of chronic constipation in men and women and the treatment of women with irritable bowel syndrome with constipation (IBS-C). Lubiprostone specifically activates type-2-chloride channels on the apical membrane of epithelial cells. Lubiprostone acts locally within the intestinal tract, is rapidly metabolized and has very low systemic bioavailability. Animal studies have demonstrated that lubiprostone increases gastrointestinal fluid secretion in a dose-dependent manner. Clinical studies performed in men and women with chronic constipation using 24 microg of lubiprostone twice-daily demonstrated objective improvement in stool frequency and consistency, as well as symptoms of straining and incomplete evacuation. A multi-center study of patients with IBS-C found that 8 microg of lubiprostone twice-daily improved both global and individual symptoms of irritable bowel syndrome. Lubiprostone is generally well tolerated and serious adverse events are rare. The most common reported side effects are nausea, headache and diarrhea. This monograph provides a brief overview on chloride channel function in the gastrointestinal tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses the safety and efficacy of this new medication for the treatment of chronic constipation and IBS-C.
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PMID:Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. 1923 88

Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (C-IBS) are commonly reported gastrointestinal (GI) disorders that have a major impact on health and quality of life. Patients experience a range of symptoms of which infrequency of bowel movement is but one and report that straining, the production of hard stools, and unproductive urges are more bothersome than stool infrequency. Additionally, in C-IBS, patients report abdominal pain and bloating as particularly troubling. Traditional treatments, such as laxatives, are often ineffective, especially in more severe constipation over the long term. In a population-based survey of constipation sufferers, half were not satisfied with their current treatment, due predominantly to poor efficacy. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists stimulate GI motility and intestinal secretion, and tegaserod has demonstrated efficacy in improving bowel habit. Tegaserod also improves constipation-associated symptoms including bloating, abdominal discomfort, stool consistency, and straining in patients with both CIC and C-IBS. However, tegaserod has been withdrawn due to an association with serious adverse cardiovascular effects. Further 5-HT(4) receptor agonists, including prucalopride and TD-5108 are in development and show exciting results in clinical studies in CIC patients, suggesting further product approvals are likely. Headache and diarrhea are the most commonly reported adverse event with this class of agent. Recently a novel prosecretory agent has been approved for the treatment of both CIC and C-IBS. Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea, diarrhea, and headache are the most commonly reported adverse events. Linaclotide also stimulates intestinal chloride secretion, but this molecule achieves this indirectly, through the activation of guanylate cyclase C. Data are emerging, but the efficacy and safety profile of this agent in the treatment of CIC and C-IBS appears encouraging.
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PMID:The use of novel promotility and prosecretory agents for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. 1944 93

Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.
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PMID:Lubiprostone: in constipation-predominant irritable bowel syndrome. 1953 39

An epidemiological study on Irritable Bowel Syndrome (IBS) was done on 411 otherwise healthy young subjects in Iceland. A questionnaire was used, based on socalled Manning's criteria for IBS (Br Med J1978; 2: 633). IBS was diagnosed if two or more of the six Manning's criteria were positive. It was asked if these criteria (symptoms) were associated with stress or required medical treatment. Furthermore the questionnaire addressed 13 other symptoms related to the gastrointestinal tract (GI). For analysis we could use answers of 400 subjects, 63.2% females, 36.8% males, most of them (93.5%) 19-29 years old. 37.9% met the criteria of IBS, and the diagnosis was significantly more often present among women (46.6%) than men (22.5%). Usually the IBS symptoms are related to stress, but few received medical treatment. All the 13 other GI symptoms are more frequent in IBS subjects than the others and there was a significant association of IBS with nausea, upper abdominal pain, bloating, constipation, painless diarrhea and flatulence. In summary, the results of this study suggest that: (i) IBS is very common among young adults in Iceland, (ii) prevalence in Iceland is higher than reported elsewhere, (hi) the female:male ratio is 2:1, (iv) stress is a precipitating factor in IBS, (v) it is suggestive that few patients with IBS seek medical attention, (vi) IBS patient have, beside classical IBS symptoms, more frequently other digestive symptoms, which are suggestive of both upper and lower GI functional disorders.
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PMID:[Irritable bowel syndrome. Epidemiological study on young people in Iceland.]. 2006 69

Drugs used for treating inflammatory bowel disease are known to have a number of gastrointestinal and liver adverse effects. 5-ASA products are relatively safe and have few adverse events. In contrast sulfasalazine has side effects in 11-40% of treated patients including fatigue, nausea, abdominal pain and diarrhoea. Glucocorticoids can induce or propagate peptic ulcers and upper GI bleeding especially in combination with NSAIDs. Thioguanins may have severe gastrointestinal side effects including gastrointestinal complaints (in up to 12%), hepatotoxicity (up to 4%) and pancreatitis (1%). Nodular regenerative hyperplasia (NRH) is an important potential side effect of thiopurine therapy especially in men with Crohn's disease after ileocecal resection. NRH may ultimately lead to portal hypertension. A major concern of methotrexate therapy in IBD besides myelosuppression and pulmonary fibrosis is hepatotoxicity. 5mg of folic acid substitution per week potentially decreases gastrointestinal side effects by 80% without interfering with the efficacy of methotrexate. Besides renal dysfunction, tremor, hirsutism, hypertension and gum hyperplasia cyclosporine is known to have a number of gastrointestinal side effects that occur with less frequency such as diarrhoea (up to 8%) nausea and vomiting (up to 10%) and hepatotoxicity in 1-4%. Rare gastrointestinal adverse events are gastritis and peptic ulcers. Paying attention to these potential deleterious side effects is mandatory for physicians treating IBD patients.
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PMID:Gastrointestinal and liver adverse effects of drugs used for treating IBD. 2022 29

Most ritonavir-boosted protease inhibitor (PI)-based antiretroviral regimens offer comparable levels of virological efficacy. Thus, the tolerability of the regimen becomes a distinguishing factor with implications for patient quality of life (QoL), treatment adherence, and clinical outcome. This article describes results from the CASTLE study (comparing once-daily atazanavir/ritonavir [ATV/RTV] with twice-daily lopinavir/ritonavir [LPV/RTV], both in combination with fixed-dose tenofovir/emtricitabine, in treatment-naive HIV-infected patients) and an evaluation of the impact of gastrointestinal (GI) complications of treatment on patient QoL, as measured by the irritable bowel syndrome (IBS) QoL questionnaire (IBS-QoL). Changes in IBS-QoL from baseline over time (to week 24) were classified as: "Improvement" (> or =2-point positive change from baseline), "No change" (<2-point change), or "Worsening" (> or =2-point negative change). Data were collected on GI adverse events (AEs) and use of GI medications. Of the 599 patients with IBS-QoL-evaluable data through week 24, fewer patients in the ATV/RTV group than in the LPV/RTV group experienced grade 2-4 treatment-related GI AEs including diarrhea (3% versus 10%), nausea (5% versus 7%), and vomiting (<1% on both arms). Nearly three times as many patients receiving LPV/RTV used GI medications. ATV/RTV was associated with an increase in overall IBS-QoL scores and more patients receiving ATV/RTV than LPV/RTV experienced improvement in IBS-QoL through week 24. In contrast to LPV/RTV, ATV/RTV treatment was associated with earlier and more positive improvements in QoL scores across CD4 sub-groups. Differences in the health-related QoL profile between ATV/RTV and LPV/RTV may be important when selecting PI-based antiretroviral regimens.
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PMID:Gastrointestinal tolerability and quality of life in antiretroviral-naive HIV-1-infected patients: data from the CASTLE study. 2046 43


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