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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    ABSTRACT: Constipation affects 14% of the adult population globally, mainly women, and significantly impacts on health-related quality of life. The causes of constipation are mainly three: lifestyle related (functional constipation), disease related, and drug induced. Constipation can generate considerable suffering, including abdominal pain and distension, anorexia, and nausea. The value of some therapeutic measures such as increased fluid intake, physical activity, diet rich in fiber, and nutritional supplements recommended for the relief of constipation is still questionable. The treatment of constipation can be carried out not only with traditional drugs but also with herbal medicines or with nutraceuticals, which are used to prevent or treat the disorder. We have reviewed the most common botanical laxatives such as senna, cascara, frangula, aloe, and rhubarb and their use in the treatment of constipation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Phytotherapy Research 07/2015; 29(10). DOI:10.1002/ptr.5410 · 2.66 Impact Factor
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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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    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.
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