title: New treatment options for chronic constipation: mechanisms, efficacy and safety.
abstract: The present review has several objectives, the first of which is to review the pharmacology and selectivity of serotonergic agents to contrast the older serotonergic agents (which were withdrawn because of cardiac or vascular adverse effects) with the newer generation serotonin receptor subtype 4 agonists. Second, the chloride ion secretagogues that act through the guanylate cyclase C receptor are appraised and their pharmacology is compared with the approved medication, lubiprostone. Third, the efficacy and safety of the application of bile acid modulation to treat constipation are addressed. The long-term studies of surgically induced excess bile acid delivery to the colon are reviewed to ascertain the safety of this therapeutic approach. Finally, the new drugs for opiate-induced constipation are introduced. Assuming these drugs are approved, practitioners will have a choice; however, patient responsiveness will be based on trial and error. Nevertheless, the spectrum of mechanisms and demonstrated efficacy and safety augur well for satisfactory treatment outcomes.
authors: College of Medicine, Mayo Clinic, Rochester, MN, USA. camilleri.michael@mayo.edu
authors: Michael
authors: M
authors: Camilleri
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism; D018118:Chloride Channels / Q000627:therapeutic use; D002908:Chronic Disease; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D000068238:Lubiprostone; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors; D010455:Peptides / Q000627:therapeutic use; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology; D058828:Serotonin 5-HT4 Receptor Agonists / Q000627:therapeutic use; D018490:Serotonin Agents / Q000627:therapeutic use; D027981:Symporters / Q000037:antagonists & inhibitors
chemical_list: D001647:Bile Acids and Salts; D018118:Chloride Channels; D005765:Gastrointestinal Agents; D007211:Indoles; D029363:Organic Anion Transporters, Sodium-Dependent; D010455:Peptides; D058828:Serotonin 5-HT4 Receptor Agonists; D018490:Serotonin Agents; D027981:Symporters; C071908:sodium-bile acid cotransporter; D044422:Receptors, Serotonin, 5-HT4; C105050:tegaserod; D000068238:Lubiprostone; D000527:Alprostadil; C523483:linaclotide