Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug development for functional gastrointestinal disorders is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of patients' symptoms, a lack of animal models of proven relevance, and safety issues. Government, patient pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the serotonin (5-HT) modifying drugs. Cisapride has been withdrawn in some countries because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists, developed to modify visceral sensation, have caused constipation; alosetron, also withdrawn, caused ischaemic colitis. The 5-HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with 'constipation-predominant' irritable bowel syndrome or idiopathic constipation. 5-HT1 agonists improve impaired gastric accommodation and symptoms in patients with functional dyspepsia. Antidepressants also affect serotonin metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with serotonin modifying drugs has been mixed, and some important lessons are there to be learnt.
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PMID:Review article: the complexity of drug development for irritable bowel syndrome. 1187 86

Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind.
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PMID:Pharmacological treatment of irritable bowel syndrome--from concept to sales. 1614 96

With the ever-growing armamentarium of pharmacological agents, the gastrointestinal drug-induced side effects of dyspepsia, nausea, vomiting, diarrhoea and constipation are increasingly seen. They are often self-limiting and without serious sequelae, but of greater concern is drug-induced mucosal ulceration that can manifest as gastrointestinal haemorrhage, stricture and perforation. These complications are mainly attributable to NSAIDs and aspirin, which can injure the mucosa anywhere along the gastrointestinal tract. These iatrogenic serious side effects can be reduced with co-prescription of a proton pump inhibitor, substitution of a COX-2 inhibitor and eradication of Helicobacter pylori when the bacterium is present. Other recognised gastrointestinal complications include small intestinal diaphragm, microscopic colitis, a range of hepatotoxic effects and pancreatitis. The introduction of new classes of drugs has resulted in new adverse effects that require consideration in patients presenting with gastroenterological symptoms. These include pill oesophagitis from bisphosphonates and ischaemic colitis relating to serotonin antagonists. Here, the authors review the literature on drug-induced complications of the gastrointestinal tract and present the pertinent management issues relevant to clinical practice.
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PMID:Drug-induced side effects affecting the gastrointestinal tract. 1677 95

Ischaemic colitis (IC) has been associated with a number of diverse disorders and risk factors, including irritable bowel syndrome (IBS) and constipation. We sought to assess, through a large-scale population study, the potential risk factors associated with IC. Patients with IC and matched controls without IC were identified using the medical and pharmacy claims data from the HealthCore Managed Care Database from 1st January 2000 to 31st May 2005. A multivariate conditional logistic regression model was developed to identify significant risk factors of IC. Interactions of age, sex, prior IBS diagnosis, and prior constipation diagnosis were further evaluated. We identified 1754 patients with IC and 6970 non-IC controls; 64% were women, and mean ages were 63 and 62 years respectively. The final parsimonious model comprised 19 independent variables associated with increased risk for IC including shock, dysentery, bloating, IBS, colon carcinoma, constipation, cardiovascular disease, dyspepsia, abdominal, aortic, or cardiovascular surgery, 12-month laxative, H(2) receptor blocker and oral contraceptive use. A significant interaction was observed between age and prior IBS on risk for IC. In conclusion, multiple risk factors for IC were identified and we confirmed that patients with IBS or constipation are at greater risk for IC.
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PMID:Assessment of potential risk factors associated with ischaemic colitis. 1791 13