Info

Increased

"Dependent upon degree of anticholinergic action.

K, decrease in conduction velocity;I, increase in conduction velocity; —, no known conduction effects;APD, action potential duration; ERP, effective refractory period (ventricular).

"Dependent upon degree of anticholinergic action.

K, decrease in conduction velocity;I, increase in conduction velocity; —, no known conduction effects;APD, action potential duration; ERP, effective refractory period (ventricular).

Sinoatrial Node and Atrial Tissue

The indirect effect of quinidine on the sinoatrial node is a result of the drug's potential to exert an anti-cholinergic action resulting in a slight increase in heart rate. Higher concentrations of quinidine have a direct effect of depressing the rate of spontaneous diastolic depolarization.

Quinidine administration results in a dose-dependent depression of membrane responsiveness in atrial muscle fibers. The maximum rate of phase 0 depolarization and the amplitude of phase 0 are depressed equally at all membrane potentials. Quinidine also decreases atrial muscle excitability in such a way that a larger current stimulus is needed for initiation of an active response. These actions of quinidine often are referred to as its local anesthetic properties.

A-V Node

Both the direct and indirect actions of quinidine are important in determining its ultimate effect on A-V conduction. The indirect (anticholinergic) properties of quinidine prevent both vagally mediated prolongation of the A-V node refractory period and depression of conduction velocity; these effects lead to enhancement of A-V transmission. Quinidine's direct electrophysio-logical actions on the A-V node are to decrease conduction velocity and increase the ERP.

His-Purkinje System and Ventricular Muscle

Quinidine can depress the automaticity of ventricular pacemakers by depressing the slope of phase 4 depolarization. Depression of pacemakers in the His-Purkinje system is more pronounced than depression of sinoatrial node pacemaker cells.

Quinidine also prolongs repolarization in Purkinje fibers and ventricular muscle, increasing the duration of the action potential. As in atrial muscle, quinidine administration results in postrepolarization refractoriness, that is, an extension of refractoriness beyond the recovery of the resting membrane potential. The indirect (an-ticholinergic) properties of quinidine are not a factor in its actions on ventricular muscle and the His-Purkinje system.

Serum K+ concentrations have a major influence on the activity of quinidine on cardiac tissue. Low extracellular K+ concentrations antagonize the depressant effects of quinidine on membrane responsiveness, whereas high extracellular K+ concentrations increase quinidine's ability to depress membrane responsiveness. This dependency may explain why hypokalemic patients are often unresponsive to the antiarrhythmic effects of quinidine and are prone to develop cardiac rhythm disorders.

Electrocardiographic Changes

At normal therapeutic plasma concentrations, quinidine prolongs the PR, the QRS, and the QT intervals. QRS and QT prolongations are more pronounced with quini-dine than with most other antiarrhythmic agents. The magnitude of these changes is related directly to the plasma quinidine concentration.

Hemodynamic Effects

Although myocardial depression is not a problem in patients with normal cardiac function, in patients with compromised myocardial function, quinidine may depress cardiac contractility sufficiently to result in a de crease in cardiac output, a significant rise in left ventricular end-diastolic pressure, and overt heart failure. Quinidine can relax vascular smooth muscle directly as well as indirectly by inhibition of ^-adrenoceptors. The depressant effects of quinidine on the cardiovascular system are most likely to occur after IV administration, and therefore, quinidine should not be employed routinely in the emergency treatment of arrhythmias. Because of its potential to cause marked depression of myocardial contractility and to decrease peripheral vascular resistance, parenteral administration of quinidine is seldom indicated.

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