Mechanisms of atrial fibrillation and action of drugs used in its management.
Drugs remain the mainstay of treatment of patients with atrial fibrillation (AF). An understanding of the mechanisms of AF and of atrioventricular (AV) conduction provides a basis for the understanding of the mechanisms of antiarrhythmic drug action. Although ectopic activity from a focus may initiate AF, re-entry is the usual mechanism of maintenance. In its classical form, reentry takes the form of circus movements around fixed anatomic structures. However, leading circle and anisotropic variants of reentry may arise as a result of functional variations of refractoriness or anistropic conduction. Electrical remodeling during AF favors its persistence. Reentry may be prevented by prolongation of the refractory period. Class III antiarrhythmic drugs prolong refractoriness by blockade of outward potassium currents. Class I drugs prolong refractoriness by delaying the recovery of of the sodium current. Many class I drugs also have potassium channel-blocking action. In AF the rate of conduction of rapid impulses to the ventricle is controlled by conduction over the AV node. Blockade of the L-type calcium channels, activation of the muscarinic and adenosine A1 receptors, or beta-adrenergic blockade will slow conduction over the AV node. The adverse cardiovascular effects of drugs used to treat AF can be predicted on the basis of their mechanisms of action. The current focus of drug development is on specific potassium channel blockers.
Grant
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Duke University Medical Center, Durham, North Carolina 27710, USA.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*; D016275:Atrial Function / Q000502:physiology; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels