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Medications for Irritable Bowel Syndrome

Initial treatments prescribed by doctors

Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opioid or opioid analogs such as loperamide, diphenoxylate or codeine in diarrhea-predominant IBS for mild symptoms.[83][84][85]

Laxatives

For patients who do not adequately respond to dietary fiber, osmotic agents such as polyethylene glycol, sorbitol, and lactulose can help avoid 'cathartic colon' which has been associated with stimulant laxatives.[86] Among the osmotic laxatives, 17 to 26 grams/day of polyethylene glycol (PEG) has been well studied.

Antispasmodics

The use of antispasmodic drugs (e.g. anticholinergics such as hyoscyamine or dicyclomine) may help patients, especially those with cramps or diarrhea. A meta-analysis by the Cochrane Collaboration concludes that if 6 patients are treated with antispasmodics, 1 patient will benefit (number needed to treat = 6).[83] Antispasmodics can be divided in two groups: neurotropics and musculotropics. Neurotropics, such as atropine, act at the nerve fibre of the parasympathicus but also affect other nerves and have side effects. Musculotropics such as mebeverine act directly at the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since this action is not mediated by the autonomic nervous system, the usual anticholinergic side effects are absent. Antispasmodic drugs are also available in combination with tranquilizers or barbiturates, such as chlordiazepoxide and Donnatal. The value of the combination therapies has not been established.

Drugs affecting serotonin

Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms.[87] Serotonin stimulates the gut motility and so agonists can help constipation predominate irritable bowel while antagonists can help diarrhea predominant irritable bowel:

Agonists

* Tegaserod, a selective 5-HT4 agonist for IBS-C, is available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. On March 30, 2007, the Food and Drug Administration (FDA) requested that Novartis Pharmaceuticals voluntarily discontinue marketing of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events (heart problems) associated with use of the drug. Novartis agreed to voluntarily suspend marketing of the drug in the United States and in many other countries. On July 27, 2007 the Food and Drug Administration (FDA) approved a limited treatment IND program for Zelnorm in the USA to allow restricted access to the medication for patients in need if no comparable alternative drug or therapy is available to treat the disease. The USA FDA had issued two previous warnings about the serious consequences of Tegaserod. In 2005, Tegaserod was rejected as an IBS medication by the European Union. Tegaserod, marketed as Zelnorm in the United States, was the only agent approved to treat the multiple symptoms of IBS (in women only), including constipation, abdominal pain and bloating. A meta-analysis by the Cochrane Collaboration concludes that if 17 patients are treated with typical doses of tegaserod, 1 patient will benefit (number needed to treat = 17).[88]
* Selective serotonin reuptake inhibitor anti-depressants (SSRIs), because of their serotonergic effect, would seem to help IBS, especially patients who are constipation predominant. Initial crossover studies[89] and randomized controlled trials[90][91][92] support this role.

Antagonists

* Alosetron, a selective 5-HT3 antagonist for IBS-D, which is only available for women in the United States under a restricted access program, due to severe risks of side-effects if taken mistakenly by IBS-A or IBS-C sufferers.
* Cilansetron, also a selective 5-HT3 antagonist, is undergoing further clinical studies in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew Cilansetron from the United States regulatory approval process after receiving a "not approvable" action letter from the FDA requesting additional clinical trials.

Other agents

Anti-depressants include both tricyclic antidepressants (TCAs) and the newer selective serotonin reuptake inhibitors (SSRIs). In addition to improving symptoms via treating any co-existing depression, TCAs have anti-cholinergic actions while SSRIs are serotonergic. Thus in theory, TCAs would best treat diarrhea-predominant IBS while SSRIs would best treat constipation-predominant IBS. A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve (number needed to treat = 3).[93] A separate randomized controlled trial found that TCAs are best for patients with diarrhea-predominant IBS.[94]

Recent studies have suggested that rifaximin can be used as an effective treatment for abdominal bloating and flatulence,[95][51] giving more credibility to the potential role of bacterial overgrowth in some patients with IBS.[96]

 


 
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