Cardiodepressive effects of antiarrhythmic drugs

Negative inotropic effects of antiarrhythmic drugs are ultimately mediated by alterations of intracellular Ca++. With class I antiarrhythmic drugs a strong correlation between the Na+ inward current and the Ca++ influx exists whereby Ca++ influx is changed by an exponent, n, of approximately 3. Generally, the longer the duration of Na+ -channel blockade the more pronounced is negative inotropy. Antiarrhythmic drugs of class I may be subdivided into those with a short recovery time of Na+ channels (lidocaine-type), those with an intermediate recovery time, such as quinidine and newer antiarrhythmics such as flecainide and propafenone, and those with a recovery time greatly exceeding 1 s, such as disopyramide and prajmaline. The degree of cardiodepression is modulated by peripheral circulatory effects such as vasoconstriction and vasodilation. In order to differentiate between general cardiodepressive effects and true negative inotropy, sophisticated methods, for example, volume-pressure relationship curves, have to be applied to determine the degree of pre- and afterload alterations, also accounting for cardiodepressive effects. The net effect of cardiodepression is due to several factors: true negative inotropy, additional influences on the peripheral circulation, the functional state of the myocardium, and the beneficial or detrimental effects on the prevailing arrhythmia. Based on these theoretical considerations, combined drug therapy of arrhythmias has to be installed under the aspect of cardiodepressive side-effects, especially in an already impaired heart.