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.

Keywords: Bile acid and salts; Constipation; Irritable bowel syndrome; Laxatives; Therapeutics.

Figure 1.

Chloride channel activation in the treatment of constipation. Reprinted from Menees et al with permission from Macmillan Publishers Ltd. ClC-2, type-2 chloride channel; CFTR, cystic fibrosis transmembrane regulator; GC-C, guanylate cyclase-C; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophosphate.

Figure 2.

The use of bile acids to treat constipation. Normally, bile acids are removed from the ileum via transporters to the liver as part of enterohepatic circulation, leading to reduced concentrations of bile acid reaching the colon and decreased colonic motility. Elobixibat inhibits the uptake of bile acids in the terminal ileum, which increases luminal concentration and improves colonic motility. Chenodeoxycholic acid is a bile acid analogue that increases the concentration of bile acid in the gut and promotes colonic motility. Modified from Menees et al with permission from Macmillan Publishers Ltd.