Quinidine (DB00908): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Quinidine is a naturally derived cinchona alkaloid and the prototypical Class IA antiarrhythmic agent, holding a unique and storied place in the history of pharmacology.[1] As the dextrorotatory stereoisomer of the antimalarial drug quinine, quinidine itself possesses a dual therapeutic legacy, having been used historically for the treatment of both cardiac arrhythmias and malaria.[1] Its primary mechanism of action involves the complex blockade of multiple cardiac ion channels, most notably the fast inward sodium current (

INa​) and several repolarizing potassium currents (e.g., IKr​, IKs​). This multi-channel blockade is the foundation for both its therapeutic efficacy in terminating reentrant arrhythmias and its significant, life-threatening proarrhythmic risk, particularly the prolongation of the QT interval and the induction of Torsades de Pointes.[1]

The clinical application of quinidine has undergone a profound paradigm shift. Once a first-line agent for common arrhythmias such as atrial fibrillation, its use was drastically curtailed following the emergence of a clear safety signal in the form of an FDA Black Box Warning detailing increased all-cause mortality in patients with non-life-threatening arrhythmias.[5] This pivotal finding has relegated quinidine to a niche but often indispensable therapeutic role. Today, it is recognized as a life-saving therapy for several rare, inherited channelopathies, including Brugada Syndrome and Short QT Syndrome, where its unique electrophysiological profile directly counteracts the underlying molecular pathology.[2]