Neurological Effects of Proton Pump Inhibitors- A Review

Abstract

Proton pump inhibitors [PPIs] are extensively used drugs for various indications. They are not approved for long term use by regulatory authorities. PPIs are also available as over the counter drugs which can lead to their inappropriate use. Amongst the adverse drug reactions [ADRs] of PPIs, dementia and Alzheimers disease [AD] are the recent ones. Inappropriate long term use of PPIs can lead to serious ADRs like myocardial infarction, nephropathy along with dementia. The possible mechanisms for PPIs induced dementia and AD are endothelial dysfunction, its aging and senescence. Effect on lysosomal function and proteostasis, shortening of telomere length, and inhibition of vacuolar ATPases [V-ATPases] of microglial lysosomal membrane also contribute for this pathology. Increased generation of beta amyloid [Aβ] peptide by inverse gama secretase modulation and augmentation of beta secretase are responsible for the generation and accumulation of Aβ along with its decreased degradation as a result of inhibition of V-ATPases in the microglia. Vitamin B 12 absorption is decreased due to long term use of PPIs. This also contributes for nerve damage as a result of impaired DNA synthesis, methylation and homocysteine neurotoxicity along with cognition impairment. Seizure like condition can be the result of hypomagnesemia induced by long term PPIs use. Thus long term, inappropriate use of PPIs invite serious and life threatening conditions which need to be kept in mind by the clinician before prescribing them.