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Basic Concepts in Cellular Cardiac Electrophysiology: Part II: Block of Ion Channels by Antiarrhythmic Drugs
Author(s) -
WHALLEY DAVID W.,
WENDT DAVID J.,
GRANT AUGUSTUS O.
Publication year - 1995
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/j.1540-8159.1995.tb06990.x
Subject(s) - medicine , drug , ion channel , pharmacology , electrophysiology , blocking (statistics) , anti arrhythmia agents , drug action , atrial fibrillation , receptor , computer science , computer network
Summary Antiarrhythmic drugs have relative specificity for blocking each of the major classes of ion channels that control the action potential. The kinetics of block is determined by the state of the channel. Those channel states occupied at depolarized potentials generally have greater affinity for the blocking drugs. The kinetics of the drug‐channel interaction is important in determining the blocking profile observed clinically. The increased mortality resulting from drug treatment in CAST and several atrial fibrillation trials has resulted in a shift in antiarrhythmic drug development from the Na + channel blocking (Class I) drugs to the K + channel blocking (Class III) drugs. While both Classes of drugs have a proarrhythmic potential, this may be less for the Class III agents. Their lack of negative inotropy also make them more attractive. It is important that the potential advantages of these agents be evaluated in controlled clinical trials. In several laboratories, the techniques of molecular biology and biophysics are being combined to determine the block site of available drugs. This information will aid in the future development of agents with greater specificity, and hopefully greater efficacy and safety than those currently in clinical use.