Luminary Learning Gastrointestinal Disorder- Issue 1

Pharmacological and Clinical Treatment of Irritable Bowel Syndrome •  19 abnormalities of the GI tract excluded, (iii) disability or restriction of daily activities due to IBS and (iv) no adequate response to conventional therapy. Ramosetron Ramosetron is a potent and selective 5-HT3 receptor antagonist, which has been initially devel- oped for the treatment of nausea and vomiting [30]. Clinical studies showed that ramosetron is effective against IBS-D. In a double-blind, placebo-controlled, parallel-group study of 418 male and female patients with IBS-D ramosetron increased the monthly responder rates of IBS symp- toms compared to placebo [31]. In another 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47 % [32]. Furthermore, the drug was active after oral administration. A long-term efficacy for overall improvement of IBS symptoms was also dem- onstrated. Seven % of patients reported adverse events after ramosetron treatment; however, no serious adverse events (severe constipation, ischemic colitis), were reported for long-term treat- ment with ramosetron [33]. Ramosetron is only licensed for use in Japan and selected Southeast Asian countries (e.g. India). Loperamide Loperamide is a synthetic peripherally-restricted MOR agonist, which does not cross the blood- brain barrier. It decreases gastric emptying, slows peristalsis, delays intestinal transit and relaxes the segmental colonic smooth muscles. On the other hand it increases fluid absorption and inhib- its intestinal secretion of electrolytes [34]. In IBS-D loperamide combats diarrhea and reduces stool frequency; however, it has only limited effect on abdominal pain. Clinical features of lop- eramide are well-established, the drug is safe and effective hence it is often recommended as a first-line therapy for functional GI disorders accompanied with diarrhea in adults. At high doses loperamide may induce constipation; therefore, the treatment starts with a relatively low dose (approx. 2 mg) and then it is titrated up or down based on the symptoms [7, 34]. Clinical studies demonstrated that loperamide is well tolerated in a 5-week therapy [35]. Trimebutine Trimebutine (used in the form of trimebutine maleate) is a weak agonist of peripheral MOR, KOR and DOR receptors, which also exhibit antimuscarinic properties [36]. Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon [37]. Clinically, trimebutine has been shown to alleviate both acute and chronic abdominal pain in patients with IBS and it may also be used in children with abdominal pain. Recently, Karabulutu et al. [36] evaluated the effect of trimebutine versus non-medication in 345 children and adolescents demonstrating the effectiveness (94.9 % patients in trimebutine group experienced significant relief) [36]. The indications for trimebu- tine include: (i) IBS, (ii) abdominal pain and abdominal cramping and (iii) dyspepsia. It may be administered in multiple doses per day with the maximal total daily dose of 600 mg.