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Agents that act luminally to treat diarrhoea and constipation

Nature Reviews Gastroenterology & Hepatology volume 9, pages 661–674 (2012)Cite this article

Subjects

Abstract

Diarrhoea and constipation are common clinical complaints that negatively affect quality of life, reduce work productivity and lead to considerable health-care expenditure. A variety of therapies have been used to treat these conditions. Unlike drugs that require systemic absorption to exert their effects, luminally acting agents improve diarrhoea and constipation by altering intestinal and/or colonic motility, as well as mucosal absorption and secretion, through a variety of mechanisms. Examples of luminally acting agents for diarrhoea include peripherally acting opiate analogues, enkephalinase inhibitors, bile-acid binding agents, nonabsorbed antibiotics, probiotics, bismuth-containing compounds, berberine and agents with possible effects on intestinal secretion or permeability. Luminally acting drugs for constipation include bulking agents, surfactants, osmotics, stimulants, chloride-channel activators, probiotics, drugs that increase delivery of bile acids to the colon and natural therapies such as prunes and hemp seed extract. As the physiological effects of luminally acting drugs are largely confined to the gastrointestinal tract, these agents are unlikely to cause adverse effects outside of the gastrointestinal tract.

Key Points

  • Luminally acting agents improve diarrhoea and constipation through effects on intestinal and colonic motility, secretion and absorption

  • As the physiological effects of these drugs are largely confined to the gastrointestinal tract, luminally acting agents might be less prone to causing nongastrointestinal adverse events

  • Drugs for diarrhoea that act luminally can affect opiate pathways, bind endogenous intestinal bile acids, alter the microbiome and modulate gut permeability

  • Luminally acting agents for constipation alter stool bulk or viscosity, provide luminal osmotic load, stimulate muscle contraction, promote intestinal chloride secretion and increase delivery of bile acids to the colon

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Figure 1: Action of opioids within the lumen of the gastrointestinal tract.
Figure 2: Aetiology and mechanism of bile acid diarrhoea.
Figure 3: Chloride-channel activation in the treatment of constipation.
Figure 4: Modulation of bile acids to treat constipation.

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  1. University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, 48109-5362, MI, USA

    Stacy Menees, Richard Saad & William D. Chey

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All authors contributed equally to researching data, discussion of content, writing the article and editing the manuscript before submission.

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Correspondence to William D. Chey.

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S. Menees declares no competing interests. R. Saad receives research support from Proctor & Gamble and Takeda Pharmaceuticals. W. D. Chey receives research support from Ironwood and acts as a consultant for Albireo, AstraZeneca, Forest, Furiex, Ironwood, Perrigo, Proctor & Gamble, Prometheus, Salix and Takeda.

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Menees, S., Saad, R. & Chey, W. Agents that act luminally to treat diarrhoea and constipation. Nat Rev Gastroenterol Hepatol 9, 661–674 (2012). https://doi.org/10.1038/nrgastro.2012.162

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