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)

Chronic constipation affects up to 27% of the population and negatively impacts health-related quality-of-life. Prescription medications targeting chronic constipation currently include polyethylene glycol, lactulose and tegaserod, a serotonin type 4 receptor partial agonist. The most recent addition is lubiprostone (Amitiza), a type-2 chloride channel (ClC-2) activator which is a member of a new class of compounds known as prostones. Lubiprostone is a bicyclic fatty acid that acts locally on ClC-2 channels located in the apical membrane of intestinal epithelial cells. This stimulation of chloride secretion induces the passive movement of sodium and water into the intestinal lumen, yielding a net increase in isotonic fluid, which results in improved bowel function. In double-blind, placebo-controlled clinical trials, lubiprostone increased the number of spontaneous bowel movements compared with placebo and was generally well tolerated. The predominant adverse effects were nausea and diarrhea. Lubiprostone represents a new therapeutic class of compounds for the treatment of chronic constipation and will be the focus of this review.
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PMID:Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation. 1726 87

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

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