Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review.

Since their approval by the Food and Drug Administration (FDA) in 1989, proton pump inhibitors (PPIs) have become one of the most highly utilized drugs in the United States, assuming a position as one of the top 10 most prescribed medications in the country. The purpose of PPIs is to limit the amount of gastric acid secreted by the parietal cells via irreversible inhibition of the H+/K+-ATPase pump, therefore maintaining an elevated gastric acid pH of greater than 4 for 15-21 h. Even though PPIs have many clinical uses, they are not without their adverse effects, mimicking achlorhydria. Besides electrolyte abnormalities and vitamin deficiencies, long-term use of PPIs has been linked to acute interstitial nephritis, bone fractures, poor COVID-19 infection outcomes, pneumonia, and possibly an increase in all-cause mortality. The causality between PPI use and increased mortality and disease risk can be questioned since most studies are observational. Confounding variables can greatly affect an observational study and explain the wide-ranging associations with the use of PPIs. Patients on PPIs are generally older, obese, sicker with a higher number of baseline morbidities, and on more medications than the compared PPI non-users. These findings suggest that PPI users are at a higher risk of mortality and complications based on pre-existing conditions. This narrative review aims to update readers on the concerning effects that proton pump inhibitor use can have on patients and give providers a resource to create informed decisions on appropriate PPI use.

Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review.

The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.