Graduation Year

2022

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Graduate School

Major Professor

Feng Cheng, Ph.D.

Committee Member

Vijaykumar Sutariya, Ph.D.

Committee Member

Sheeba Varghese Gupta, Ph.D.

Keywords

bradycardia risk, mechanism of action, drug administration, covid-19

Abstract

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see which group of patients were at a higher risk for bradycardia. This study also sought to determine whether variables including sex, dosage, and concurrent drugs affected the risk of bradycardia. According to the findings, individuals who received remdesivir were considerably more likely to report bradycardia than those who received any other COVID-19 treatment medication. The likelihood of reporting bradycardia was not significantly influenced by sex or remdesivir dose. Potential drug-drug interactions were identified with remdesivir therapy, and this included Levetiracetam (ROR = 3.51, 95% CI 1.72-7.16), Tamsulosin (OR = 3.18, 95% CI 1.82-5.5), and Tocilizumab (OR = 2.07, 95% CI 1.35-3.17). The primary mechanisms of actions that impart higher bradycardia risk when using remdesivir were postulated to be lowering sinus node automaticity through vagal stimulation and mitochondrial dysfunction caused by drug-induced cardiotoxicity. The findings of the study revealed a strong association between remdesivir use and bradycardia in adults, as well as the underlying biological processes and genes that cause bradycardia in response to remdesivir administration.

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