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ask if patients with gas and bloating are drinking too much carbonated beverages, drinking with a straw or chewing gum, all of which can lead to aerophagia, advise against excessive intake of fats, which can lead to gas retention, advise against eating certain carbohydrates, such as beans, cabbage, broccoli and cauliflower, which may lead to fermentation and gas in the colon, and encourage patients with constipation to increase fiber intake. Studies suggest this can help relieve constipation but not relieve pain. Drug therapy Consider drug therapy to reduce pain and diarrhea or consti- pation even though the effectiveness of most pharmacologic agents may be limited. In a study of 350 patients with IBS, more than half (55%) taking prescription drugs for IBS felt that they were ineffective or only somewhat effective. More than 60% reported adverse effects, and 40% taking over-thecounter medications reported they were ineffective. The FDA has only approved two drugs, tegaserod maleate and alosetron hydrochloride, both of which now have restricted use. Tegaserod, a 5-HT4-receptor agonist, was approved for treatment of constipation-predominant IBS but is restricted because of an association with myocardial infarction and stroke. Alosetron, a 5-HT3-receptor antagonist, was approved for diarrhea-predominant IBS but has been restricted because of a 1 in 700 risk of ischemic colitis. Prescribing Drug treatment for irritable bowel syndrome physicians must register with the manufacturer and patients must sign a consent form to begin therapy. Other drugs may provide relief for some patients with IBS. These include antispasmodics, laxatives, antidiarrheals, antidepressants and antibiotics. (See table, “Drug treatment for irritable bowel syndrome.”) Consider antispasmodics as a first-line agent for pain since they reduce contractions in the colon. The two available in the U.S. are dicyclomine and hyoscyamine. They should be taken before meals if postprandial urgency, diarrhea and cramping are problems. Saline-type laxatives may help patients with constipation that is not responsive to increased fiber intake. One study showed that daily administration of low-dose polyethylene glycol laxatives increases bowel frequency and decreases symptoms in chronic constipation. Expert consensus suggests that osmotic laxatives such as magnesium citrate or sodium phosphate are safe and effective for severe constipation when used daily or as needed. Regular use of stimulant cathartics such as senna, cascara and phenolphthalein should be avoided because they can cause cramps. Agent Mechanism of action Dosage Benefits Antispasmodics Reduce contractions in colon and small bowel which may produce diarrhea and cramps Generally given prn, especially before meals Reduce pain Dicyclomine Reduce contractions in colon and small bowel which may produce diarrhea and cramps 10-20 mg po before meals Reduce pain Hyoscyamine Reduce contractions in colon and small bowel which may produce diarrhea and cramps 1.25 mg po before meals prn or 0.125 sl 3.75 mg xl po bid Reduce pain Combination antispasmodic/ sedative Additive effect of sedative to reduce GI motility 1-2 po q6h prn Useful for pain, especially if patient anxious and antispasmodics alone have failed Clidinium bromide/ chlordiazepoxide (Librax) Additive effect of sedative to reduce GI motility Before meals or q6h prn Useful for pain, especially if patient anxious and antispasmodics alone have failed Phenobarbital, hyoscyamine, atropine, scopolamine (Donnatal) Additive effect of sedative to reduce GI motility Useful for pain, especially if patient Same phenobarbital, 16 mg; anxious and antispasmodics alone hyoscyamine, 0.1 mg; atropine, 0.02 mg; scopolamine, 0.006 mg have failed Laxatives Colon lavage prn or scheduled Reduces distention of colon due to retained stool Saline cathartics: Polyethylene glycolelectrolyte solution (Miralax), GoLytely Magnesium based, phosphate based, PEG Titrate to effect Reduces distention of colon due to retained stool. PEG-based lavage solutions useful for severe constipation taken a few glasses qhs Osmotic cathartics: Sorbitol Sorbitol 30%, lactulose Titrate to effect Reduces distention of colon due to retained stool. PEG-based lavage solutions useful for severe constipation taken a few glasses qhs Anti-diarrheals Mu opiate agonists have primarily gut Titrate to effect effect to increase segmenting contractions and decrease propulsive ones Reduces diarrhea Loperamide Mu opiate agonist phenylpiperidine 1-2 po q6h prn diarrhea, titrate to effect Has been shown to reduce diarrhea but not pain FOLLOW-UP Diphenoxylate/Atropine Mu opiate agonist with anticholinergic 1-2 po q6h prn diarrhea, titrate to effect. Diphenoxylate, 2.5 mg; atropine, 0.025 mg Reduces diarrhea Cholestyramine Bile acid binder and nonspecific constipating agent 4 g po qd to bid to start, titrate to effect Reduces diarrhea Serotonin-3 antagonists: Alosetron Reduces intestinal pain sensitivity in animals. Helps diarrhea-predominant IBS in women. Reduces gut transit and increases colon compliance 1 mg po bid Reduces pain and diarrhea. Appears to be effective only in women. Improves quality of life Reassess patients with IBS over time to ensure that a more serious disorder is not being overlooked. Determine that symptoms are not progressive and that red flag symptoms have not developed. Reassure the patient that there are no long-term complications or risk of cancer associated with IBS even though IBS symptoms are typically chronic and fluctuating in severity. Carefully consider the need for diagnostic tests or referral if symptoms are refractory and persistent. Serotonin-4 antagonists: Tegaserod Stimulates peristalsis and accelerates gut transit mouth to cecum via 5HT-4 receptor in enteric nervous system 6 mg po bid Relief of constipation-predominant IBS symptoms, especially constipation and pain to a lesser degree. Antibiotics: Neomycin IBS symptoms may be related to intestinal bacterial overgrowth 500 mg bid x 10 days 200 mg, 2 tabs tid for 10 days Rifaximin Tricyclic anti-depressants Reduce pain and diarrhea, mechanism unknown. Not mediated by depression treatment Doses needed are lower than depression doses Amitriptyline 10-100 mg qhs Desipramine 10-100 mg qhs Trazodone 10-100 mg qhs IBS symptoms may be related to intestinal bacterial overgrowth. Several double-blind studies have shown that the antibiotics rifaximin and neomycin improve IBS symptoms. However, neomycin only works in 25% of patients and has side effects that limit its use, making rifaximin the preferred choice. In addition, IBS patients with preexisting psychiatric problems such as depression may benefit from tricyclic antidepressants. Best results are obtained with a low starting dose, then gradual increases as tolerated. Using selective serotonin reuptake inhibitors may increase the quality of life for patients with severe IBS and associated psychological distress. PATIENT EDUCATION Patient education can help patients with IBS. Explain the connection between IBS and previous gastrointestinal infection and bacterial overgrowth. Explain that IBS generally is a chronic condition and that patients can help themselves by taking medication as needed, eliminating diet triggers and understanding psychological triggers. This information comes from the PIER module “Irritable Bowel Syndrome” (http://pier.acponline.org). The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP. 10-100 mg qhs Doxepin SSRIs Reduced pain, especially in diarrheapredominant IBS Loperamide is a first-line agent for diarrhea symptoms. It can be taken as needed or on a scheduled basis depending on severity and frequency. Other opioid antidiarrheal agents, such as diphenoxylate hydrochloride combined with atropine sulfate, also may be effective. Unknown; may increase gut compliance or have psychological action Depression doses and lower doses have been used May reduce pain. Effective for depression if present See PIER for side effects and other notes bid = twice daily; CNS = central nervous system; GI = gastrointestinal; IBS = irritable bowel syndrome; po = oral; qd = once daily; qhs = every night; sl = sublingual. 9