Systematic review: cardiovascular safety profile of 5- HT4 agonists developed for gastrointestinal disorders.

Autor: Tack, J., Camilleri, M., Chang, L., Chey, W. D., Galligan, J. J., Lacy, B. E., Müller‐Lissner, S., Quigley, E. M. M., Schuurkes, J., Maeyer, J. H., Stanghellini, V.
Předmět:
Zdroj: Alimentary Pharmacology & Therapeutics; Apr2012, Vol. 35 Issue 7, p745-767, 23p, 1 Diagram, 3 Charts
Abstrakt: Summary Background The nonselective 5- HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events ( AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5- HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5- HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5- HT4 agonists had reports of cardiovascular AEs: cisapride ( QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5- HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5- HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5- HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5- HT4 agonists for GI disorders differ in chemical structure and selectivity for 5- HT4 receptors. Selectivity for 5- HT4 over non-5- HT4 receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5- HT4 agonists may offer improved safety to treat patients with impaired GI motility. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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