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• W2045080045 abstract "An increasing confluence of experimental and clinical data on the gravity of proarrhythmic effects of class I agents has led to a shift to other electrophysiologic classes of agents for treating cardiac arrhythmias. The fact that β blockers reduce mortality in a variety of subsets of patients has suggested a wider role for this class of agents. Recent investigations have focused on the potential role of sotalol and amiodarone, 2 agents that not only block sympathetic antagonism, but also prolong cardiac repolarization. They have been test drugs in an increasing number of controlled and uncontrolled trials in patients at risk for arrhythmic deaths. Their properties have formed the basis for the hypothesis that arrhythmias may be effectively controlled independently of changes in conduction; they are prototypes of compounds that may favorably influence electrical instability in the myocardium. Amiodarone and sotalol are, however, complex molecules with attendant side effects; therefore, attention is also focusing on compounds that act simply by selective prolongation of cardiac repolarization. These agents have been termed “pure” class III agents. The properties of sotalol, the prototype of class III agents, are of particular interest because it is a racemic mixture wtth the levo-isomer having 50 times the β-blocking potency of the dextro-isomer; both have equipotent class III actions. Studies of the antiarrhythmic properties of β blockers, d- and d,l-sotatol, and amiodarone may provide insights into the nature of class III actions. There is clinical evidence indicating that class III drugs exert a varying spectrum of antifibrillatory and proarrhythmic (characterized by torsades de pointes) actions for a given degree of prolongation of repolarization. These differences currently are not explicable in terms of the specificity of their actions on ionic channels. There are differences between the socalled pure class III agents such as sematilide, dofetilide, and E-4031 and more complex compounds such as sotatel and amiodarone, which also exert antiadrenergic actions. In the development of newer drugs an appropriate balance needs to be struck between their proarrhythmic actions and their antifibrillatory properties. At present, it is unclear whether such antifibrillatory compounds should be relatively simple molecules with clearly defined electrophysiologic profiles in terms of actions on ion channels, currents, receptors, and pumps, or whether it may be more desirable to develop agents wtth complex electropharmacologic profiles with a multiplicity of actions. The available data suggest that sotalol and amiodarone are superior to class I agents and have the potential to reduce arrhythmia mortality." @default.
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• W2045080045 date "1993-11-01" @default.
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• W2045080045 title "Controlling cardiac arrhythmias by lengthening repolarization: Historical overview" @default.
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• W2045080045 doi "https://doi.org/10.1016/0002-9149(93)90960-k" @default.
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