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)

Exenatide is the first in a new class of compounds that exhibit activity similar to the naturally occurring hormone glucagon-like peptide-1 (GLP-1). Released from cells in the gut in response to food, GLP-1 binds to pancreatic beta-cell receptors to stimulate the release of insulin. Exenatide mirrors many of the effects of GLP-1, improving glycemic control through a combination of mechanisms, which include glucose-dependent stimulation of insulin secretion, suppression of glucagon secretion, slowing of gastric emptying, reduced appetite and enhanced beta-cell function. As stimulation of insulin secretion occurs only in the presence of elevated blood glucose concentrations, the risk of hypoglycemia should be greatly reduced with exenatide. In addition to positive therapeutic effects on fasting and postprandial glucose levels, exenatide treatment is associated with significant, dose-dependent reductions in glycated hemoglobin (HbA1c) from baseline and progressive reductions in body weight. Exenatide is generally well tolerated; nausea is the most commonly reported side effect, but it can be significantly reduced when a target dose of exenatide is achieved in patients with gradual dose titration. Exenatide may enable patients with type 2 diabetes to achieve glycemic control while reducing or eliminating the risk of hypoglycemia and weight gain. These would represent significant therapeutic gains.
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PMID:Exenatide. 1634 Dec 88

The association between migraine and functional gastrointestinal disorders has been confirmed by many clinical observations and epidemiological studies. In most patients during the attacks of migraine, apart from various neurological and vascular symptoms, gastrointestinal disturbances occur including nausea, vomiting, abdominal pain or diarrhea. Functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), are reported in migraine patients in periods between the attacks as well. On the other hand 23-53% of IBS patients have frequent headaches. Migraine and IBS often coexist with fibromyalgia and other chronic pain syndromes and functional disorders. Migraine and IBS affect approximately 10-20% of the general population, usually young adults. Both diseases are more prevalent in women, perhaps due to the role of estrogen in their pathogenesis. Looking for the common pathogenetic mechanisms of IBS and migraine the role of the brain-gut axis, neuroimmune and neuroendocrine interactions are being considered. The influence of stress on symptom occurrence and severity seems to be associated with hyperactivity of the hypothalamic-pituitary-adrenal axis. The enteric nervous system as a source of numerous neurotransmitters and visceral reflexes is a plausible common pathogenic link between IBS and migraine. In particular serotonin being the main neurotransmitter of the gastrointestinal tract plays a relevant role in the pathogenesis of IBS as well as migraine. Nowadays, agonists and antagonists of serotoninergic receptors are the most efficacious drugs for IBS and migraine therapy. Some side effects of triptans, 5-HT(1B/D) agonists, used in migraine treatment may be connected with the influence of triptans on the gastrointestinal functions. A better understanding of the relationship between migraine and IBS may result in more effective treatment of both diseases.
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PMID:[Migraine and irritable bowel syndrome]. 1641 71

Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.
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PMID:Reassessment of functional dyspepsia: a topic review. 1671 48

Dyspepsia comprises a broad spectrum of predominantly upper abdominal symptoms, such as pain, indigestion, nausea, early satiety and bloating. While these symptoms are highly prevalent, in less than 50% of patients presenting with dyspepsia, structural lesions or biochemical abnormalities are found that explain the symptoms when routine clinical tests are used. In patients without structural lesions the diagnosis of functional dyspepsia is justified. Exclusion of life-threatening disorders as the cause of symptoms and reassurance of the patient as well as proper explanation of the diagnosis and its underlying disease mechanisms (i.e. symptoms are due to a sensitive gut) is crucial and can be considered as an essential element of treatment. Since there is a remarkable comorbidity of anxiety and depression, psychosomatic interventions might be necessary in selected patients. Based on controlled clinical trials few drugs, such as proton pump inhibitors, prokinetics, tricyclic antidepressants, simethicone and selected herbal preparations have been found to be effective for treatment of functional dyspepsia. Effects of H. pylori eradication, even though strongly advocated, are most likely due to undiagnosed peptic ulcer disease in a very small group of patients. While there is currently no therapy that cures functional dyspepsia, the therapeutic target is to control symptoms.
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PMID:[Functional dyspepsia - diagnosis of desperation?]. 1676 73

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea (P=.2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed >or=1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.
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PMID:Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD). 1692 May 59

Incretin mimetics are a new class of pharmacological agents with multiple antihyperglycemic actions that mimic several of the actions of incretin hormones originating in the gut, such as glucagon-like peptide (GLP)-1. Dipeptidyl peptidase-IV (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. These agents seem to have multiple mechanisms of action for the treatment of type 2 diabetes mellitus (T2DM), including some or all the following: enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and decreased food intake. Exenatide (BYETTA) is the first incretin mimetic approved for clinical use by the US Food and Drug Administration. In phase 3 clinical trials, exenatide reduced HbA(1c) by approximately 1% and body weight by approximately 2 kg in T2DM patients failing to achieve glycemic control with metformin and/or a sulfonylurea, with mild-to-moderate nausea the most common side effect. Several GLP-1 analogues and DPP-IV inhibitors are in late-stage clinical testing and may soon become available for treating T2DM patients. The use of these agents may provide an opportunity to bring about new improvements in diabetes care.
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PMID:Incretin mimetics and DPP-IV inhibitors: new paradigms for the treatment of type 2 diabetes. 1709 Jul 94

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.
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PMID:The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. 1725 57

Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central nervous system. However, the predominant site of serotonin synthesis, storage, and release is the enterochromaffin cells of the intestinal mucosa. Within the intestinal mucosa, serotonin released from EC cells activates neural reflexes associated with intestinal secretion, motility, and sensation. Two important receptors for serotonin that are located in the neural circuitry of the intestines are the 5-HT(3) and 5-HT(4) receptors; these are the targets of drugs designed to treat gastrointestinal disorders. 5-HT(3) receptor antagonists are used to treat nausea and emesis associated with chemotherapy and for functional disorders associated with diarrhea. 5-HT(4) receptor agonists are used as promotility agents to promote gastric emptying and to alleviate constipation. Because of the importance of serotonin in normal gut function and sensation, a number of studies have investigated potential changes in mucosal serotonin signaling in pathologic conditions. Despite the inconsistencies in the current literature, changes in serotonin signaling have now been demonstrated in inflammatory bowel disease, irritable bowel syndrome, postinfectious irritable bowel syndrome, and idiopathic constipation. Emerging evidence has led to many contradictory theories regarding serotonin signaling and its roles in the pathology of gut disorders. This review summarizes the current medications affecting serotonin signaling and provides an overview of our current knowledge of the changes in serotonin that occur in pathologic conditions.
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PMID:Serotonin and its role in colonic function and in gastrointestinal disorders. 1719 2

Serotonin is an important gastrointestinal signaling molecule. It is a paracrine messenger utilized by enterochromaffin (EC) cells, which function as sensory transducers. Serotonin activates intrinsic and extrinsic primary afferent neurons to, respectively, initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is also a neurotransmitter utilized by a system of long descending myenteric interneurons. Serotonin is synthesized through the actions of 2 different tryptophan hydroxylases, TpH1 and TpH2, which are found, respectively, in EC cells and neurons. Serotonin is inactivated by the serotonin reuptake transporter (SERT)-mediated uptake into enterocytes or neurons. The presence of many serotonin receptor subtypes enables selective drugs to be designed to therapeutically modulate gastrointestinal motility, secretion, and sensation. Current examples include tegaserod, a 5-HT(4) partial agonist, which has been approved for treatment of irritable bowel syndrome (IBS) with constipation in women and for chronic constipation in men and women. The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea. Serotonergic signaling abnormalities have also been putatively implicated in the pathogenesis of functional bowel diseases. Other compounds, for which efficacy has not been rigorously established, but which may have value, include tricyclic antidepressants and serotonin selective reuptake inhibitors to combat IBS, and 5-HT(1) agonists, which enhance gastric accommodation, to treat functional dyspepsia. The initial success encountered with serotonergic agents holds promise for newer and more potent insights and therapies of brain-gut disorders.
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PMID:The serotonin signaling system: from basic understanding to drug development for functional GI disorders. 1724 88

Tegaserod, a selective and partial agonist at the 5-hydroxytryptamine (5-HT [serotonin]) receptor subtype 4 (5-HT4), is the only United States Food and Drug Administration-approved drug for the treatment of constipation-predominant irritable bowel syndrome (IBS) in women. The drug's stimulation of 5-HT4 receptors on intestinal enterocytes increases peristaltic activity and fluid secretion into the gut lumen, facilitating stool passage. In addition, affinity of tegaserod for 5-HT4 receptors modulates visceral sensitivity, which helps alleviate abdominal pain associated with constipation-predominant IBS. The drug's pharmacokinetic and pharmacodynamic parameters do not differ significantly with age or sex. Tegaserod safely and effectively relieves overall gastrointestinal symptoms and abdominal discomfort and normalizes bowel habits in patients with constipation-predominant IBS. It is associated with few drug interactions. In clinical studies, tegaserod was well tolerated, and its adverse-effect profile was similar to that of placebo. Severe diarrhea, as well as abdominal pain, flatulence, headache, and nausea, were the most commonly reported events. Patients who experience severe diarrhea should discontinue the drug. With the data available, tegaserod remains an option for patients with constipation-predominant IBS.
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PMID:Tegaserod for constipation-predominant irritable bowel syndrome. 1725 16


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