title: Novel therapies for constipation.
abstract: Constipation is a common medical problem and when standard laxatives fail it can be difficult to treat. Different aetiologies require tailored therapeutic approaches. Simple constipation may only require dietary manipulation while severe neurological or slow transit constipation may need pharmacologic intervention. Recently new drug therapies have been introduced. PubMed and Ovid were searched for reviews, systematic reviews and meta-analysis published since 2003 using the terms: constipation, prucalopride, linaclotide and lubiprostone. This review summarizes potential novel therapies identified as effective in the management of chronic constipation. Prucalopride is a selective 5-hydroxytryptamine receptor agonist. The prucalopride study was in patients, largely women with idiopathic constipation showed improved spontaneous complete bowel movement (SCBM) at a dose of 2 mg a day with few adverse events reported. Linaclotide is a 14-amino acid peptide guanylate cyclase-C agonist. The linaclotide study was carried out in patients with irritable bowel syndrome, constipation group (IBS-C). There was significant improvement of bowel evacuation and symptom resolution in patients on the active treatment arm. Lubiprostone activates type-2 chloride channels, increasing intestinal fluid secretion. In the trials of this drug, the lubiprostone arms had a greater mean number of SCBM. The novel therapies, prucalopride, lubiprostone, and linaclotide had very different modes of action yet, all three have been shown to be efficacious and safe in the treatment dose for constipation.
authors.affiliation: Sreedhari Thayalasekeran, Hani Ali, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, Cottingham HU165JQ, United Kingdom.
authors.forename: Sreedhari
authors.initials: S
authors.lastname: Thayalasekeran
authors.affiliation: Sreedhari Thayalasekeran, Hani Ali, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, Cottingham HU165JQ, United Kingdom.
authors.forename: Hani
authors.initials: H
authors.lastname: Ali
authors.affiliation: Sreedhari Thayalasekeran, Hani Ali, Her-Hsin Tsai, Department of Gastroenterology, Castle Hill Hospital, Cottingham HU165JQ, United Kingdom.
authors.forename: Her-Hsin
authors.initials: HH
authors.lastname: Tsai
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use; D002120:Calcium Channel Agonists / Q000627:therapeutic use; D003248:Constipation / Q000188:drug therapy* / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects*; D020536:Enzyme Activators / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D000068238:Lubiprostone; D010455:Peptides / Q000627:therapeutic use; D058828:Serotonin 5-HT4 Receptor Agonists / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001572:Benzofurans; D002120:Calcium Channel Agonists; D020536:Enzyme Activators; D005765:Gastrointestinal Agents; D010455:Peptides; D058828:Serotonin 5-HT4 Receptor Agonists; C406662:prucalopride; D000068238:Lubiprostone; D000527:Alprostadil; C523483:linaclotide
keywords: Constipation; Linaclotide; Prucalopride