Irritable Bowel Syndrome - Management - Medication

Medication

Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opiate, opioid, or opioid analogs such as loperamide, codeine, diphenoxylate) in diarrhea-predominant IBS for mild symptoms and stronger opiates such as morphine and oxycodone for severe cases.

Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms. 5HT3 antagonists such as ondansetron are effective in post-infectious IBS and diarrhoea dominant IBS due to their blockade of serotonin on 5HT3 receptors in the gut; the reason for their benefit is believed to be because excessive serotonin in the gut is believed to play a role in the pathogenesis of some subtypes of IBS. Benefits may include reduced diarrhoea, reduced abdominal cramps and improved general wellbeing. Any nausea present may also respond to 5HT3 antagonists due to their antiemetic properties. Serotonin stimulates the gut motility and so agonists can help constipation-predominate irritable bowel, while antagonists can help diarrhea-predominant irritable bowel. Selective serotonin re-uptake inhibitors, SSRI's, frequently prescribed for panic and/or anxiety disorder and depression, affect serotonin in the gut as well as the brain. The bowels are highly dependent on serotonin for neural communication. The National Institute of Health issued a report stating: Selective serotonin re-uptake inhibitor antidepressants seem to promote global well being in some patients with irritable bowel syndrome and, possibly, some improvement in abdominal pain and bowel symptoms, but this effect appears to be independent of improved depression. Further research is required.

Laxatives

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

Lubiprostone (Amitiza), is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well tolerated in adults, including elderly patients. As of July 20, 2006, Lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). Unlike many laxative products, Lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration.

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 seven patients are treated with antispasmodics, one patient will benefit. Antispasmodics can be divided in two groups: neurotropics and musculotropics.

• Neurotropics, such as a phenobarbital like Donnatal or 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.

Tricyclic antidepressants

There is strong evidence that low doses of tricyclic antidepressants can be effective for irritable bowel syndrome. However, there is less robust evidence as to the effectiveness of other antidepressant classes such as SSRIs.

Serotonin agonists

• Tegaserod (Zelnorm), 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 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 tegaserod 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.
• 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 and randomized controlled trials support this role.

Serotonin antagonists

Alosetron, a selective 5-HT3 antagonist for IBS-D and cilansetron (also a selective 5-HT3 antagonist) were trialed for irritable bowel syndrome. Due to severe adverse effects, namely ischemic colitis and severe constipation, they are not available or recommended for irritable bowel syndrome.

Other agents

Magnesium aluminum silicates and alverine citrate drugs can be effective for irritable bowel syndrome.

There is conflicting evidence about the benefit of antidepressants in IBS. Some meta-analysis have found a benefit while others have not. A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve. A separate randomized controlled trial found that TCAs are best for patients with diarrhea-predominant IBS.

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

Domperidone, a dopamine receptor blocker and a parasympathomimetic, has been shown to reduce bloating and abdominal pain as a result of an accelerated colon transit time and reduced faecal load, that is a relief from hidden constipation; defecation was similarly improved.

The use of opioids is controversial due to the potential risk of tolerance, physical dependence and addiction but can be the only relief for some diarrhea predominant cases when other treatment has been ineffective.

SIBO Therapy

Studies demonstrated statistically significant reduction in IBS smyptoms following therapy for Small intestinal bacterial overgrowth.