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)

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

The gastrointestinal transit can be disturbed in different situations by increased or decreased motility patterns. Pharmacological treatment of gastrointestinal motility disorders is intended to inhibit or stimulate motility. Prokinetic agents as metoclopramide, domperidone, erythromycin or tegaserod are used in clinical settings. We discuss their use in functional dyspepsia and gastroparesis. Management of chronic constipation consists of increasing fluid and dietary fiber intake and increasing physical activity. Fiber, lubricants, osmotic and stimulative laxatives increase stool frequency and improve symptoms of constipation. Treatment of irritable bowel syndrome (IBS) should focuses on the specific gastrointestinal complaints. In constipation predominant IBS fiber and isoosmotic laxatives are used first line. Tegaserod has an advantage over placebo in constipation-predominant IBS. Pain can be treated with antispasmodic agents and tricyclic antidepressants in low doses. The diarrhea-predominant IBS responds well to a loperamide treatment.
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PMID:[Pharmacologic treatments of transit disorders]. 1766 10

Three patients, two women aged 33 and 75 years and a 62-year-old man, presented with gallstones and upper abdominal pain due to functional dyspepsia, chronic constipation, and oesophageal spasm, respectively. After a period of watchful waiting, the first patient insisted on having a cholecystectomy, but her complaints persisted. In the second patient, the complaints disappeared after treatment with a bulking agent and magnesium oxide. The third patient received medication as well: a proton-pump inhibitor, prokinetic agents, a calcium antagonist and Helicobacter eradication, and recovered. The presence of gallstones is relatively easy to assess by ultrasound imaging, but the decision whether abdominal symptoms are related to gallbladder stones remains a diagnostic challenge for the clinician. The key question for the family practitioner, gastroenterologist and surgeon is which patients with upper abdominal pain and proven gallbladder stones might benefit from a cholecystectomy. The patients described illustrate that upper abdominal pain is not invariably related to symptomatic gallbladder disease. The published evidence supports initial watchful waiting with additional diagnostic investigation, and cholecystectomy only later if judged to be necessary.
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PMID:[Patients with upper abdominal pain and echographically-proven gallstones: start with expectative management]. 1772 79

Typical and atypical symptoms from acid reflux, dyspepsia, chronic constipation, fecal incontinence, and irritable bowel syndrome are extremely common in adults and remain so in the geriatric population. The presence of these problems may have profound effects on the functional status, independence, and quality of life in the vulnerable older population, making it essential for physicians to inquire actively about them and to be able to recognize atypical presentations when appropriate. This article summarizes the definitions, epidemiology, clinical presentation, and impact of these common problems in the geriatric patient.
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PMID:Chronic gastrointestinal symptoms in the elderly. 1792 34

Serotonin (5-hydroxytryptamine or 5-HT) plays a critical physiological role in the regulation of gastrointestinal (GI) function. 5-HT dysfunction may also be involved in the pathophysiology of a number of functional GI disorders, such as chronic constipation, irritable bowel syndrome and functional dyspepsia. This article describes the role of 5-HT in the enteric nervous system (ENS) of the mammalian GI tract and the receptors with which it interacts. Existing serotonergic therapies that have proven effective in the treatment of GI functional disorders and the potential of drugs currently in development are also highlighted. Advances in our understanding of the physiological and pathophysiological roles of 5-HT in the ENS and the identification of selective receptor ligands bodes well for the future development of more efficacious therapies for patients with functional GI disorders.
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PMID:Serotonin pharmacology in the gastrointestinal tract: a review. 1839 1

Dyspepsia is a highly prevalent condition characterized by symptoms originating in the gastroduodenal region without underlying organic disorder. Treatment modalities include acid-suppressive drugs, gastroprokinetic drugs, Helicobacter pylori eradication therapy, tricyclic antidepressants, and psychological therapies. Irritable bowel syndrome is a multifactorial, lower functional gastrointestinal disorder involving disturbances of the brain-gut axis. The pathophysiology provides the basis for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, intraluminal changes, and mucosal immune activation. Medications targeting chronic constipation or diarrhea may also relieve irritable bowel syndrome. Novel approaches to treatment require approval, and promising agents are guanylate cyclase cagonists, atypical benzodiazepines, antibiotics, immune modulators, and probiotics.
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PMID:Current medical treatments of dyspepsia and irritable bowel syndrome. 2095 13

The recently published Rome III criteria reflect current understanding of functional gastrointestinal disorders. These criteria include definitions of these conditions and their pathophysiologic subtypes and offer guidelines for their management. At the 2006 Annual Scientific Meeting of the American College of Gastroenterology, a panel of experts discussed these criteria as they pertain to irritable bowel syndrome, functional dyspepsia, and chronic constipation. This article reviews the panel's findings, highlights the differences between the Rome II and III criteria, and summarizes best treatment options currently available to practitioners and their patients.
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PMID:All Roads Lead to Rome: Update on Rome III Criteria and New Treatment Options. 2154 52

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.
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PMID:Cellular and molecular basis of chronic constipation: taking the functional/idiopathic label out. 2386 72

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.
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PMID:Disorders of gastrointestinal hypomotility. 2758 35

Gas, bloating, and belching are associated with a variety of conditions but are most commonly caused by functional gastrointestinal disorders. These disorders are characterized by disordered motility and visceral hypersensitivity that are often worsened by psychological distress. An organized approach to the evaluation of symptoms fosters trusting therapeutic relationships. Patients can be reliably diagnosed without exhaustive testing and can be classified as having gastric bloating, small bowel bloating, bloating with constipation, or belching disorders. Functional dyspepsia, irritable bowel syndrome, and chronic idiopathic constipation are the most common causes of these disorders. For presumed functional dyspepsia, noninvasive testing for Helicobacter pylori and eradication of confirmed infection (i.e., test and treat) are more cost-effective than endoscopy. Patients with symptoms of irritable bowel syndrome should be tested for celiac disease. Patients with chronic constipation should have a rectal examination to evaluate for dyssynergic defecation. Empiric therapy is a reasonable initial approach to functional gastrointestinal disorders, including acid suppression with proton pump inhibitors for functional dyspepsia, antispasmodics for irritable bowel syndrome, and osmotic laxatives and increased fiber for chronic idiopathic constipation. Nonceliac sensitivities to gluten and other food components are increasingly recognized, but highly restrictive exclusion diets have insufficient evidence to support their routine use except in confirmed celiac disease.
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PMID:Gas, Bloating, and Belching: Approach to Evaluation and Management. 3081 Nov 60


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