Skip to Main content Skip to Navigation
Journal articles

Chronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis

Abstract : Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship. Several mechanisms have been suggested through in vitro studies (endothelial dysfunction, endothelial senescence, hypomagnesemia, increase of chromogranin A levels, decrease of nitric oxide in endothelial cells) leading to the impairment of vascular homesostasis, paving the way to these complications. Evidence that PPIs may have off-targets and pleiotropic effects are mounting and may impose a cautious attitude in the prescription of PPI's, especially in elderly and/or in the context of chronic use.
Document type :
Journal articles
Complete list of metadatas

Cited literature [52 references]  Display  Hide  Download

https://hal-amu.archives-ouvertes.fr/hal-01664284
Contributor : Patrice Roll <>
Submitted on : Thursday, March 29, 2018 - 3:11:17 PM
Last modification on : Friday, October 23, 2020 - 4:49:11 PM

File

THERAP-S-17-00102.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Farid Kheloufi, Diane Frankel, Elise Kaspi, Marion Lepelley, Michel Mallaret, et al.. Chronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis. Thérapie, EDP Sciences, In press, ⟨10.1016/j.therap.2017.08.003⟩. ⟨hal-01664284⟩

Share

Metrics

Record views

319

Files downloads

706