Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Association between Molecular Initiating Events (MIEs) in Drug-Induced Hiccups

Version 1 : Received: 12 February 2024 / Approved: 14 February 2024 / Online: 15 February 2024 (01:25:14 CET)

A peer-reviewed article of this Preprint also exists.

Hosoya, R.; Ishii-Nozawa, R.; Terajima, T.; Kagaya, H.; Uesawa, Y. The Association between Molecular Initiating Events and Drug-Induced Hiccups. Pharmaceuticals 2024, 17, 379. Hosoya, R.; Ishii-Nozawa, R.; Terajima, T.; Kagaya, H.; Uesawa, Y. The Association between Molecular Initiating Events and Drug-Induced Hiccups. Pharmaceuticals 2024, 17, 379.

Abstract

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

Keywords

drug-induced hiccups; FAERS; nuclear receptor; stress response pathways

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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