9: Quinidine

INTRODUCTION

Quinidine was one of the first agents used for its antiarrhythmic effects. It is classified as a type IA antiarrhythmic agent and can be used for the treatment of supraventricular or ventricular arrhythmias.¹ After ventricular rate has been controlled, quinidine therapy can be used to chemically convert atrial fibrillation to normal sinus rhythm for a patient.² Because of its side effect profile, quinidine is considered by many clinicians to be a second-line antiarrhythmic choice. Quinidine inhibits transmembrane sodium influx into the conduction system of the heart, thereby decreasing conduction velocity.^1,3 It also increases the duration of the action potential, increases threshold potential toward zero, and decreases the slope of phase 4 of the action potential. Automaticity is decreased during quinidine therapy. The net effect of these cellular changes is that quinidine causes increased refractoriness and decreased conduction in heart conduction tissue which establishes a bidirectional block in reentrant pathways.

THERAPEUTIC AND TOXIC CONCENTRATIONS

When given intravenously, the serum quinidine concentration-time curve follows a two-compartment model.^{4,5,6, and 7} However, due to marked hypotension and tachycardia when given intravenously to some patients, the oral route of administration is far more common. When oral quinidine is given as a rapidly absorbed dosage form such as quinidine sulfate tablets, a similar distribution phase is also observed with a duration of 20-30 minutes.^4,5,8,9 If extended-release oral dosage forms are given, absorption occurs more slowly than distribution so a distribution phase is not seen (Figure 9-1).^{10,11,12,13, and 14}

The generally accepted therapeutic range for quinidine is 2-6 μg/mL. Quinidine serum concentrations above the therapeutic range can cause increased QT interval or QRS complex widening (>35%-50%) on the electrocardiogram, cinchonism, hypotension, high-degree atrioventricular block, and ventricular arrhythmias. Cinchonism is a collection of symptoms that includes tinnitus, blurred vision, lightheadedness, tremor, giddiness, and altered hearing which decreases in severity with lower quinidine concentrations. Gastrointestinal adverse effects such as anorexia, nausea, vomiting, and diarrhea are the most common side effects of quinidine therapy, can occur ...