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5 Serotonin receptor agonists and antagonists Serotonin is an important mediator of gastrointestinal motility and sensation Alosetron and tegaserod modulate serotonin pathways However, in 2007, tegaserod was withdrawn by the FDA from the US market after an analysis of safety data from over 18,000 patients in 29 clinical trials showed an excessive number of serious cardiovascular side effects Alosetron is a 5-HT3 antagonist that is FDA-approved for the treatment of women with severe irritable bowel syndrome with predominant diarrhea It appears to alter visceral sensation through blockade of peripheral 5-HT3-receptors on enteric afferent neurons and inhibits enteric cholinergic motor neurons, resulting in inhibition of colonic motility Alosetron (1 mg twice daily) reduces symptoms of pain, cramps, urgency, and diarrhea in 50 60% of women compared with 30 40% treated with placebo Efficacy in men has not been demonstrated In contrast to the excellent safety profile of other 5-HT3 antagonists (eg, ondansetron), alosetron may cause constipation (sometimes severe) in 30% of patients or ischemic colitis in 4:1000 patients Given the seriousness of these side effects, alosetron is restricted to women with severe irritable bowel syndrome with diarrhea who have not responded to conventional therapies and who have been educated about the relative risks and benefits of the agent It should not be used in patients with constipation 6 Nonabsorbable antibiotics A randomized controlled study reported symptom improvement in 40% of patients treated with the nonabsorbable antibiotic rifaximin, 400 mg three times daily for 10 days, compared with a 25% improvement in placebo-treated patients Improvement persisted over a 10-week follow-up period Symptom improvement may be attributable to suppression of bacteria in either the small intestine or colon At this time, the pathologic importance of small intestinal bacterial overgrowth and the therapeutic role of antibiotics in irritable bowel syndrome are controversial If bacterial overgrowth is suspected, some clinicians may order a lactulose hydrogen breath test to confirm the diagnosis Others may administer an empiric trial of rifaximin therapy Still others may choose to defer evaluation or treatment pending further clinical studies 7 Probiotics Small controlled clinical trials report improved symptoms in some patients treated with one probiotic, Bifidobacterium infantis, but not with another probiotic, Lactobacillus salivarius, or placebo It is hypothesized that alterations in gut flora may reduce symptoms through suppression of inflammation or reduction of bacterial gas production, resulting in reduced distention, flatus, and visceral sensitivity Such therapy is attractive because it is safe, well tolerated, and inexpensive A randomized, controlled trial confirmed global symptom improvement in approximately 60% of patients treated with B infantis (108 bacteria/capsule once daily), compared with 40% treated with placebo Although promising, further study is needed to define the efficacy and optimal formulations of probiotic therapy.



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severe symptoms that do not respond to conservative measures These agents should be viewed as being adjunctive rather than curative Given the wide spectrum of symptoms, no single agent is expected to provide relief in all or even most patients Nevertheless, therapy targeted at the specific dominant symptom (pain, constipation, or diarrhea) may be beneficial 1 Antispasmodic agents Anticholinergic agents are used by some practitioners for treatment of acute episodes of pain or bloating despite a lack of well-designed trials demonstrating efficacy Available agents include hyoscyamine, 0125 mg orally (or sublingually as needed) or sustained-release, 0037 mg or 075 mg orally twice daily; dicyclomine, 10 20 mg orally; or methscopolamine 25 5 mg orally before meals and at bedtime Anticholinergic side effects are common, including urinary retention, constipation, tachycardia, and dry mouth Hence, these agents should be used with caution in the elderly and in patients with constipation 2 Antidiarrheal agents Loperamide (2 mg orally three or four times daily) is effective for the treatment of patients with diarrhea, reducing stool frequency, liquidity, and urgency It may best be used prophylactically in situations in which diarrhea is anticipated (such as stressful situations) or would be inconvenient (social engagements) 3 Anticonstipation agents Treatment with osmotic laxatives (milk of magnesia or polyethylene glycol) may increase stool frequency, improve stool consistency, and reduce straining Lactulose or sorbitol produces increased flatus and distention, which are poorly tolerated in patients with irritable bowel syndrome Patients with intractable constipation should undergo further assessment for slow colonic transit and pelvic floor dysfunction (see Constipation, above) 4 Psychotropic agents Patients with predominant symptoms of pain or bloating may benefit from low doses of tricyclic antidepressants, which are believed to have effects on motility, visceral sensitivity, and central pain perception that are independent of their psychotropic effects Because of their anticholinergic effects, these agents may be more useful in patients with diarrhea-predominant than constipation-predominant symptoms Nortriptyline, desipramine, or imipramine, may be started at a low dosage of 10 mg at bedtime and increased gradually to 50 150 mg as tolerated Response rates do not correlate with dosage, and many patients respond to doses of 50 mg daily Side effects are common, and lack of efficacy with one agent does not preclude benefit from another Improvement should be evident within 4 weeks The serotonin reuptake inhibitors (sertraline, 50 150 mg daily; paroxetine 10 20 mg daily; or fluoxetine, 20 40 mg daily) may lead to improvement in overall sense of well-being but have little impact on abdominal pain or bowel symptoms Anxiolytics should not be used chronically in irritable bowel syndrome because of their habituation potential Patients with major depression or anxiety disorders should be identified and treated with therapeutic doses of appropriate agents.

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Patients with anorexia nervosa may exhibit severe emaciation and may complain of cold intolerance or constipation Amenorrhea is almost always present Bradycardia, hypotension, and hypothermia may be present in severe cases Examination demonstrates loss of body fat, dry and scaly skin, and increased lanugo body hair Parotid enlargement and edema may also occur

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Laboratory findings are variable but may include anemia, leukopenia, electrolyte abnormalities, and elevations of blood urea nitrogen (BUN) and serum creatinine Serum cholesterol levels are often increased Endocrine abnormalities include depressed levels of luteinizing and follicle-stimulating hormones and impaired response of luteinizing hormone to luteinizing hormone-releasing hormone

The diagnosis can be difficult, since many common social and cultural factors promote and maintain anorexic behavior The diagnosis depends on identification of the common behavioral features and exclusion of medical disorders that would account for weight loss Behavioral features required for the diagnosis include intense fear of becoming obese, disturbance of body image, weight loss of at least 15%, and refusal to exceed a minimal normal weight The differential diagnosis includes endocrine and metabolic disorders, such as panhypopituitarism, Addison s disease, hyperthyroidism, and diabetes mellitus; gastrointestinal disorders, such as Crohn s disease and celiac sprue; chronic infections and cancers, such as tuberculosis and lymphoma;

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