Agents that act luminally to treat diarrhoea and constipation

University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109-5362, USA.
Nature Reviews Gastroenterology &#38 Hepatology (Impact Factor: 12.61). 09/2012; 9(11). DOI: 10.1038/nrgastro.2012.162
Source: PubMed


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.

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Available from: William Chey, Apr 29, 2015
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    • "Anti-Parkinson's disease drugs, antihypertensive, monoamine oxidase inhibitors, antipsychotics , and ganglionic blockers act by altering the release or the effect of neurotransmitters on the intestinal mucosa and smooth muscle layers (Brunton et al., 2011). Drugs like cholestyramine act to lower the serum cholesterol by binding luminal bile acids, which stimulate fluid secretion (Menees et al., 2012). Iron, bismuth, and other heavy metals cause constipation, but their mechanism is not clear. "
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    • "Chloride channel activation in the treatment of constipation. Reprinted from Menees et al32 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. "
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