[Unwanted cardiovascular effects of anti-arrhythmia agents]

Abstract

Antiarrhythmic drugs can cause many undesirable side effects affecting a number of organs and functions. Of those which affect the cardiovascular system, the proarrhythmic and negative inotropic effects are the most serious. Proarrhythmic effects, suggested by an aggravation of an arrhythmia or the induction of a previously undocumented arrhythmia, may be favorised by the presence of an arrhythmogenic substrate (unidirectional lock, delayed conduction, dual conduction pathways, low thresholds of depolarisation or fibrillation, presence of zones of hyperautomaticity...), "triggering" mechanisms (extrasystoles, variations of heart rate, after-depolarisation) and by changes in the cardiac environment (variations of autonomic nervous tone and hormonal changes, electrolytic or metabolic disorders...). An antiarrhythmic may have a beneficial action on one of these factors (for example, suppression of extrasystoles) but an aggravating effect on others (for example, an increase in the heart rate, creation of zones of reentry). This probably explains the fact that, for the moment, only molecules which have multifactorial modes of action have been shown to be beneficial in arrhythmias after myocardial infarction. Negative inotropic effects may be directly responsible for a deterioration in the hemodynamic status of patients on antiarrhythmics and indirectly responsible for aggravating arrhythmia by altering the anatomical substrate, so favorising proarrhythmic effects. The negative inotropic action may be related to ionic mechanisms (lowering intracellular calcium concentration due to blockade of the sodium channel by Class I antiarrhythmics) or to indirect mechanisms (reduced sympathetic tone, non-specific beta inhibition, calcium channel blockade, decreased left ventricular compliance, vasoconstrictor effects...).(ABSTRACT TRUNCATED AT 250 WORDS)