Robert H. Heissenbuttel

The effect of oral quinidine on intraventricular conduction in man: Correlation of plasma quinidine with changes in QRS duration☆

The effect of quinidine on QRS and Q-T durations was studied in relation to the plasma concentration achieved when the drug was administered orally (200 to 400 mg. every 6 hours) to 20 patients with cardiac arrhythmias. Changes from control in QRS duration (ΔQRS) and the rate corrected Q-T interval (ΔQ-Tc) were repeatedly measured during the initial 3 days of therapy utilizing an oscilloscopic time expanded display. The plasma quinidine concentrations ranged from 1.3 to 5.4 μg per milliliter; plasma concentrations considered antiarrhythmic were obtained in every patient (> 2.4 μg per milliliter). Antiarrhythmic effect was demonstrated when arrhythmias were abolished in 10 of 20 patients. Every patient showed a statistically significant increase in QRS and Q-T durations after quinidine. The mean maximal ΔQRS was 12 msec. and ΔQ-Tc was 101 msec. QRS duration increased as a function of plasma quinidine concentration (df = 93, r = 0.56, p < 0.001). Although statistically significant, the correlation of ΔQ-Tc with plasma quinidine concentration was not nearly as high as that seen with ΔQRS. Quinidine-induced slowing of intraventricular conduction, manifested by increased QRS duration, was seen in every patient even at plasma concentrations of 2 to 5 μg per milliliter. Such plasma concentrations are almost invariably achieved in patients given maintenance doses of quinidine sulfate.

Intermittent Intravenous Procaine Amide to Treat Ventricular Arrhythmias: Correlation of Plasma Concentration with Effect on Arrhythmia, Electrocardiogram, and Blood Pressure

Abstract Twenty patients with ventricular arrhythmias were treated with procaine amide to determine an antiarrhythmic plasma drug concentration range and to observe procaine amides effect on blood...

New Drugs: Bretylium Tosylate: A Newly Available Antiarrhythmic Drug for Ventricular Arrhythmias

Bretylium tosylate (Bretylol) has recently been approved for parenteral use against resistant ventricular arrhythmias. The pharmacologic action of bretylium is complex, and its antiarrhythmic action differs significantly from other drugs. Bretylium is an adrenergic neuronal blocking agent taken up selectively at peripheral adrenergic nerve terminals, where it initially releases norepinephrine (sympathomimetic effect) and then produces adrenergic neuronal blockade. It has direct cardiac membrane effect to prolong action potential duration and effective refractory period but, unlike other membrane active antiarrhythmic agents, does not depress conduction velocity or automaticity. Bretylium increases ventricular fibrillation threshold and prevents the decrease in ventricular fibrillation threshold associated with myocardial ischemia. It does not depress myocardial contractility. Clinical studies have shown parenteral bretylium to be effective in suppressing ventricular arrhythmias, particularly recurrent, drug resistant ventricular tachycardia or ventricular fibrillation.

Clinical Use of Antiarrhythmic Drugs

Fundamental to treatment of cardiac arrhythmias are a precise diagnosis of the rhythm abnormality, knowledge of its natural history, and understanding of the cardiac effects of the antiarrhythmic drugs. The mechanisms of most arrhythmias are as yet undefined. Quinidine, procaine amide, propranolol, diphenylhydantoin and lidocaine are the commonly used antiarrhythmic drugs.

Quinidine-Digoxin Interaction-Reply

We would like to reply to the comments by Matzke and Burkle and those by Cisneros. Matzke and Burkle have reservations regarding the incidence of the interaction. We have made no attempt to state the actual incidence of this interaction; a retrospective study of hospitalized cardiac patients cannot possibly establish a true incidence. We have simply reported the finding of 25 cases in a single medical center in a single year, which suggests to us that the interaction must be common. Based on their mathematical model, Drs Matzke and Burkle expected higher serum digoxin concentrations than we found. The implication of this comment is that serum digoxin concentration may have risen merely from institution of a higher dose, enforced patient compliance in the hospital, or increased absorption from changes in other medications. We do not belive this to be the case for the following reasons: First, the baseline