2019 Volume 72 Issue 10 Pages 600-608
New pharmacological therapeutics are needed to achieve substantial relief of constipation symptoms and normalization of gastrointestinal motility. In recent years, several new agents with novel mechanisms of action that are both efficacious and safe have been approved in Japan for the treatment of chronic constipation.
Osmotic laxatives, such as polyethylene glycol (PEG) and lactulose, contain poorly absorbed molecules that draw water into the intestinal lumen, thus softening stool and increasing intestinal transit. A systematic review found that PEG was superior to both placebo and lactulose in adults and children. The most common adverse events for PEG include distension and diarrhea, whereas lactulose commonly causes dose-dependent abdominal cramping and bloating.
Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea and diarrhea are the most commonly reported adverse events. Linaclotide is a minimally absorbed agonist of guanylate cyclase-C that reduces symptoms associated with irritable bowel syndrome with constipation. Elobixibat exerts its novel mechanism of action by blocking the ileal absorption of bile acids, which ultimately increases the flow of bile into the colon, causing increased intestinal secretions and transit.
