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

“…[2][3][4][5] 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. 6,7 However, the treatments are still unsatisfactory in some patients. Recently, the involvement of microbial factors, such as alterations in the gut microbiota, has been suggested as a possible etiological mechanism.…”

“…25,26 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. 6,25,27 The 5-HT 4 receptor agonist prucalopride accelerates colonic transit and has been effective in patients with chronic constipation. 28,29 Mosapride citrate (mosapride) is a selective 5-HT 4 receptor agonist, and its metabolite has a weak 5-HT 3 receptor antagonistic effect.…”

“…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 .…”

Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders

“…87 Bile acids that are not absorbed in the terminal ileum can stimulate water and electrolyte secretion in the colon and directly contribute to colonic motility independent of secretory effects. 104 A subset of patients with IBS-C may exhibit lower bile acid levels in their stools than in those of healthy controls and of patients with diarrhoea-predominant IBS, 87 which may be attributed to altered bile acid synthesis in these patients. 105 Modulation of the bile acid cycle may help treat chronic constipation and involves bile acid supplementation or inhibition of the ileal bile acid transporter.…”