PharmacovigilanceChronic use of proton pump inhibitors, adverse events and potential biological mechanisms: A translational analysis
Section snippets
Abbreviations
- ADMA
asymmetrical dimethylarginine
- ARIC
atherosclerosis risk in communities
- CANTAB
CAmbridge Neuropsychological Test Automated Battery
- CgA
chromogranin-A
- CKD
chronic kidney disease
- DDAH
dimethylarginine dimethylaminohydrolase
- DMSO
dimethyl sulphoxide
- eGFR
estimated glomerular filtration rate
- eNOS
endothelial nitric oxyde synthaseGHS Geisinger health system
- GHS
Geisinger health system
- iNOS
inducible nitric oxyde synthase
- NO
nitric oxide
- NOS
nitric oxide synthase
- PPIs
proton pump inhibitors
- PS
propensity score
Conclusion
Even though in vivo studies are still required to understand and clarify the underlying mechanisms of such effects, the available fundamental and clinical data regarding drug safety should be considered. Actions should be undertaken particularly because these drug safety issues meet a body of evidence around the misuse and overprescribing of PPIs worldwide. As written by Lanas, even if the most of these adverse events have been mainly detected in observational studies, these potential adverse
Disclosure of interest
The authors declare that they have no competing interest.
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Cited by (14)
Does Alzheimer's disease stem in the gastrointestinal system?
2021, Life SciencesCitation Excerpt :It has been estimated that approximately 40–60% of all PPI prescriptions are unnecessary and, patients continue to take these medications, mostly without any reassessment of the need to continue prescribing [168]. A number of pharmacoepidemiological studies have indicated that long-term exposure to PPIs can be associated with the development of dementia [169–171]. Notwithstanding, there are few studies addressing the underlying mechanism linking PPI utilization and dementia.
Esomeprazole reduces sperm motility index by targeting the spermic cholinergic machinery: A mechanistic study for the association between use of proton pump inhibitors and reduced sperm motility index
2020, Biochemical PharmacologyCitation Excerpt :Several recent studies have shown that esomeprazole is well tolerated [21–24], and used together with two antibiotics for the eradication of H. Pylori infection in patients with duodenal ulcers [25–27]. Nonetheless, several reports associate prolonged use of PPIs with increased risk of hip fracture, clostridium difficile infections, iron and B12 deficiency, as well as cognitive impairment, and incidence of dementia in elderly [28–33]. Other reports indicate that PPIs can significantly affect sperm quality, total sperm motility, sperm concentration and can lead to infertility [34–36].
Proton pump inhibitors and cardiovascular adverse effects: Real or surreal worries?
2020, European Journal of Internal MedicineCitation Excerpt :Several mechanisms impairing vascular homeostasis have been suggested to account for the complications of chronic PPI use, including endothelial dysfunction and senescence, decrease of nitric oxide (NO) in endothelial cells, hypomagnesemia, and an increase of chromogranin A (CgA) levels (Fig. 1). The evidence that PPIs may have off-targets and pleiotropic effects is growing, potentially leading to a cautious attitude in the prescription of PPIs, especially in the elderly, at high doses, and/or for long-term use [42]. A study on human microvascular endothelial-cell cultures found that PPI administration increased the production of free radicals by impairing the lysosomal proton pump of the endothelium, while chronic exposure (81 days) to PPIs accelerated human endothelial senescence by reducing telomere length [43].
Laparoscopic antireflux surgery (LARS) is highly effective in the treatment of select patients with chronic cough
2019, Surgery (United States)Citation Excerpt :The guidelines of the American College of Chest Physicians endorse conservative measures for initial management, including dietary modifications of less than 45 g of fat per day, abstinence from trigger foods (coffee, tea, soda, chocolate, mints, citrus fruits, and alcohol), and cessation of smoking.27 When medical therapy is necessary, the American College of Chest Physicians recommends PPIs as first-line treatment, although there is increasing evidence for substantial adverse effects associated with chronic PPI therapy.12,28–30 The role of operative intervention in management of chronic cough associated with GERD is presently recommended only for those individuals who fail medical management.