Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Sultana, Janetca
- dc.contributor.author Calabro, Marcoca
- dc.contributor.author Garcia-Serna, Ricardca
- dc.contributor.author Ferrajolo, Carmenca
- dc.contributor.author Crisafulli, Concettaca
- dc.contributor.author Mestres i López, Jordica
- dc.contributor.author Trifirò, Gianlucaca
- dc.date.accessioned 2018-07-13T07:51:50Z
- dc.date.available 2018-07-13T07:51:50Z
- dc.date.issued 2017
- dc.description.abstract INTRODUCTION: Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. AIM: The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. METHODS: A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. RESULTS: The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. CONCLUSION: Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sultana J, Calabró M, Garcia-Serna R, Ferrajolo C, Crisafulli C, Mestres J et al. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses. PLoS One. 2017 Oct 27;12(10):e0187034. DOI: 10.1371/journal.pone.0187034
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0187034
- dc.identifier.issn 1932-6203
- dc.identifier.uri http://hdl.handle.net/10230/35146
- dc.language.iso eng
- dc.publisher Public Library of Science (PLoS)ca
- dc.relation.ispartof PLoS One. 2017 Oct 27;12(10):e0187034
- dc.rights Copyright © 2017 Sultana et al. This is an open access article distributed under the terms of the https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Pneumònia
- dc.title Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analysesca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion