Long term PPI use : Associated risks

Proton pump inhibitors (PPI) are often self-prescribed by the patients and since PPIs are available over-the-counter, patients can have free access to them and for long periods of time, without seeking medical attention. Although guidelines for OTC use suggest a short course (2 week treatment) of PPIs in patients with typical complaints (acid and/or regurgitation), and without alarm symptoms, great potential for misuse and/or overuse does exist. PPIs as a class end in the suffix, “prazole”, e.g. pantoprazole, omeprazole, lansoprazole, esomeprazole, etc.

chronic PPI use

Potential complications of chronic PPI use

Potential adverse effectPlausible underlying biological mechanism
Risk of fractureReduced calcium absorption in the duodenum and proximal jejunum as a consequence of achloridria
HypomagnesaemiaPoorly defined (gastrointestinal malabsorption and renal wasting)
Vitamin B12 deficiencyReduced acid-activated proteolytic digestion in the stomach related to reduced absorption
DementiaHigh levels of amyloid-β and deposition of amyloid-β peptides in brains of animal models
Cardiovascular riskCompetitive metabolism effect on cytochrome P450
Renal diseaseUnclear (deposit of PPIs or their metabolites in the kidney’s tubulo-interstitium stimulating immune response)
C. difficile infectionReduce gastric acidity may promote bacterial colonization in the GI tract
PneumoniaPotential micro-aspiration or translocation into the lungs from upper GI bacterial overgrowth
Fundic gland polypsTrophic effect of high gastrin levels on GI mucosa
Gastric cancerPossible synergic effect of PPI treatment and Helicobacter pylori infection
Colon cancerTrophic effect of high gastrin levels on colon cancer cells in vitro

Further reading:

Eusebi, L. H.Rabitti, S.Artesiani, M. L.Gelli, D.Montagnani, M.Zagari, R. M., and Bazzoli, F. (2017Proton pump inhibitors: Risks of long-term useJournal of Gastroenterology and Hepatology3212951302. doi: 10.1111/jgh.13737.

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