Dataset Information

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

ABSTRACT:

Background

The nonselective 5-HT(4) 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-HT(4) 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UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data.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-HT(4) 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-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride).

Conclusions

5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.

SUBMITTER: Tack J

PROVIDER: S-EPMC3491670 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Tack J J Camilleri M M Chang L L Chey W D WD Galligan J J JJ Lacy B E BE Müller-Lissner S S Quigley E M M EM Schuurkes J J De Maeyer J H JH Stanghellini V V

Alimentary pharmacology & therapeutics 20120222 7

<h4>Background</h4>The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs).<h4>Aim</h4>To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy.<h4>Methods</h4>Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 ...[more]

PMID: 22356640

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Project description:BackgroundThe association between socioeconomic status (SES) and health is well-documented; however limited evidence on the relationship between SES and gastrointestinal (GI) infections exists, with published studies producing conflicting results. This systematic review aimed to assess the association between SES and GI infection risk, and explore possible sources of heterogeneity in effect estimates reported in the literature.MethodsMEDLINE, Scopus, Web of Science and grey literature were searched from 1980 to October 2015 for studies reporting an association between GI infections and SES in a representative population sample from a member-country of the Organisation for Economic Co-operation and Development. Harvest plots and meta-regression were used to investigate potential sources of heterogeneity such as age; level of SES variable; GI infection measurement; and predominant mode of transmission. The protocol was registered on PROSPERO: CRD42015027231.ResultsIn total, 6021 studies were identified; 102 met the inclusion criteria. Age was identified as the only statistically significant potential effect modifier of the association between SES and GI infection risk. For children, GI infection risk was higher for those of lower SES versus high (RR 1.51, 95% CI;1.26-1.83), but there was no association for adults (RR 0.79, 95% CI;0.58-1.06). In univariate analysis, the increased risk comparing low and high SES groups was significantly higher for pathogens spread by person-to-person transmission, but lower for environmental pathogens, as compared to foodborne pathogens.ConclusionsDisadvantaged children, but not adults, have greater risk of GI infection compared to their more advantaged counterparts. There was high heterogeneity and many studies were of low quality. More high quality studies are needed to investigate the association between SES and GI infection risk, and future research should stratify analyses by age and pathogen type. Gaining further insight into this relationship will help inform policies to reduce inequalities in GI illness in children.

Dataset Information

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Background

Aim

Methods

Results

Conclusions

Publications

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Similar Datasets

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