Reviews for Primary Care - Fall 2007 - (Page 17) Chronic Constipation and Functional Bowel Disorders Apical Basolateral CFTR Cl channel CIC-2 Cl channel Cl K Na -K -2Cl Cl Cotransporter Na Na pump K K channel Na Paracellular path Na Cl K () Lubiprostone Figure 5. Lubiprostone mechanism of action. Used with permission from Cuppoletti J et al.28 agonists and prostaglandins have side effects that limit their clinical utility, including crampy abdominal pain. Lubiprostone, a chloride channel activator, does not seem to share this characteristic.27 Lubiprostone is a member of a new class of bicyclic fatty acid prostaglandin E1 derivatives known as prostones. Lubiprostone is derived from a metabolite of prostaglandin E1, although it has no effects on smooth muscle contractions like its PGE1 counterpart. Lubiprostone is minimally absorbed from the gastrointestinal tract and appears to act intraluminally to activate ClC-2 channels located on the apical membrane of intestinal epithelial cells (Figure 5).28,29 When it is activated, an efflux of chloride through the ClC-2 channels promotes secretion into the lumen of the intestinal tract. To maintain electrical neutrality, sodium ions follow through a paracellular pathway. Water passively follows, to maintain isotonicity. Thus, the net effect of activating the ClC-2 channels is intestinal fluid secretion, which adds fluid to stool and promotes increased transit, likely through stimulation of local receptors sensitive to stretch and distention. The Role of Diagnostic Tests in Identifying Functional Gastrointestinal Disorders: An Updated Review Utilizing Rome Criteria to Augment Prudent Clinical Practice Although many clinicians use the Rome criteria in clinical practice, they are not meant to replace good clinical history-taking to identify presenting symptoms, establish a timeline, identify the presence of alarm features, and review dietary habits and medications (Table 3).10,30 Colonoscopy Use in Patients With Constipation In 2005 the American College of Gastroenterology Chronic Constipation Task Force indicated that empiric treatment without performance of invasive diagnostic testing was a reasonable approach to a patient with symptoms of chronic constipation without alarm signs or symptoms.31 According to the task force, these “red flag” alarm signs or symptoms indicating the need for a colonoscopy include31: • New-onset constipation in an elderly patient • Severe, persistent constipation that is unresponsive to empiric treatment • Family history of colon cancer or inflammatory bowel disease • Hematochezia • Positive fecal occult blood test • Unexplained anemia • Weight loss of 10 or more pounds Colonoscopy is one of the most common tests performed by gastroenterologists but is not in itself a test to explain why someone has chronic constipation. Few data exist evaluating the yield of colonoscopy in terms of identifying organic disease in patients with chronic constipation, and the data that do exist do not indicate that colonoscopy affects outcomes in Table 3 Key Points of the Clinical History and Physical Examination Clinical History • • • • Physical Examination Signs of systemic and local diseases that might cause constipation Assess the structure and function of the anorectum and pelvic floor muscles Other relevant abnormalities Presenting symptoms • Establish history timeline Presence of alarm signals • Family history: IBS, organic gastrointestinal disorder • • Diet • Review medications being taken Adapted from Cash BD et al.30; Locke GR III et al.10 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 17
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