Emerging Pharmacologic Therapies for Constipation-predominant Irritable Bowel Syndrome and Chronic Constipation

Abstract

Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies.

Efficacy of combination therapy with probiotics and mosapride in patients with IBS without diarrhea: a randomized, double‐blind, placebo‐controlled, multicenter, phase II trial

“…IBS is considered a multifactorial disorder associated with visceral hypersensitivity, altered gut motility, and dysfunction of the brain–gut axis and immune system . In the past, therapy has been symptom‐based, but recent advances in the understanding of the pathophysiology have led to the development of therapies directed at specific phenotypes of IBS, such as serotonergic agents and prosecretory agents . However, the treatments are still unsatisfactory in some patients.…”

“…Dysfunction of serotonergic signaling is considered important in the pathogenesis of IBS and has been a therapeutic target . Studies have shown that serotonergic agents, acting primarily through 5‐HT 3 and 5‐HT 4 receptors, provide clinical benefit to patients with functional GI disorders including IBS . The 5‐HT 4 receptor agonist prucalopride accelerates colonic transit and has been effective in patients with chronic constipation .…”

Risk Factors for Postoperative Ileus Following Orthopedic Surgery: The Role of Chronic Constipation

“…[19][20][21] The highly selective 5-hydroxytryptamine receptor 4 agonist, prucalopride, has been indicated for the treatment of chronic constipation, especially in patients who do not experience adequate relief with laxatives. 22 In a phase II trial for POI, 317 patients who underwent partial colectomy were administered 0.5-, 2-, or 4-mg prucalopride once daily until the third day post-surgery. Compared with the placebo group, the 4-mg prucalopride group showed a faster gastrointestinal motility recovery time and a 10% increase in the number of patients released from the hospital within 6 days.…”

Repeated Water Avoidance Stress Alters Mucosal Mast Cell Counts, Interleukin-1β Levels with Sex Differences in the Distal Colon of Wistar Rats

“…33 The use of a balanced proportion of male and female rodents in preclinical studies and application of sex-based analysis are needed to elucidate sex-related differences in the pathophysiological mechanism of IBS. In addition, as the response of new drug for IBS and constriction is known to be different depending on sex [40][41][42][43] this approach will be more important and useful. The limitations of this experiment are as follows: we did not exactly measure the amount of food intake per day, which is reported to be linked with the frequency and amount of fecal pellets, and which can influence the body weight gain in the last 5 days of the experiment.…”