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Chapter 8 Medical Pharmacology: Antiarrhythmic Agents
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How do Antiarrhythmic Drugs Work?
Although for a given arrhythmia in a patient the mechanism may not be known, there are certain general explanations for the action of anti-arrhythmic agents.
Antiarrhythmic drugs may work by:
(a) Suppressing initiation site (automaticity/after-depolarizations) and/or
(b) Preventing early or delayed afterdepolarizations and/or
(c) By disrupting a re-entrant pathway.
(a)
Automaticity: Automaticity may be diminished by:
(1) Increasing the maximum diastolic membrane potential
(2) Decreasing the slope of phase 4 depolarization
(3) Increasing action potential duration
(4) Raising the threshold potential
All of these factors make it take longer or make it more difficult for the membrane potential to reach threshold.
(1) The diastolic membrane potential may be increased by adenosine and acetylcholine.
(2) The slope of phase 4 depolarization may be decreased by beta receptor blockers
(3) The duration of the action potential may be prolonged by drugs that block cardiac K+ channels
(4) The membrane threshold potential may be altered by drugs that block Na+ or Ca2+ channels.
(b)
Delayed or Early Afterdepolarizations:
Delayed or early afterdepolarizations may be blocked by factors that
(1) prevent the conditions that lead to afterdepolarizations.
(2) directly interfere with the inward currents (Na+, Ca2+) that cause afterdepolarizations.
(c)
Reentry
For anatomically-determined re-entry such as Wolf-Parkinson-White syndrome (WPW) drugs the arrhythmia can be resolved by blocking action potential (AP) propagation. (In WPW syndrome, an accessory conduction pathway, linking atria and ventricles and bypassing the atrioventricular node, is the structure responsible for the arrhythmia)
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In WPW-based arrhythmias, blocking conduction through the AV node may be clinically effective.
Drugs that prolong nodal refractoriness and slow conduction include: Ca2+ channel blockers, beta-adrenergic blockers, or digitalis glycosides.
For functional (non-anatomical) reentrant circuits, prolongation of refractoriness is the electrophysiological change most likely to terminate the reentry arrhythmia.
Prolongation of tissue refractoriness can be accomplished by
those antiarrhythmic drugs that block Na+
channels.
Sodium channel blockers reduces the percentage of recovered channels (following inactivation by depolarization) at any given membrane potential.
Examples of antiarrhythmic drugs classified as sodium channel blockers include lidocaine, quinidine, and tocainide.
"Although any type
of arrhythmia can occur in a patient with WPW, the two most
common are CMTs (circus
movement tachycardias) and atrial fibrillation (AFib).
CMT is the more common arrhythmia of the two
Treatment of CMTs associated with WPW is similar to treating PSVT
In a stable patient, adenosine (rapid IV push; if unsuccessful, repeat after dosage adjustment rapid IV push) should be the first-line treatment in any regular tachycardia, regardless of whether the complex is wide or narrow
Treatment of AFib associated with WPW is necessarily different than for a patient with a normal heart. AFib is an irregular rhythm as opposed to the regular rhythm seen in CMTs.
The basic treatment principle in WPW AFib is to prolong the anterograde refractory period of the accessory pathway relative to the AV node. This slows the rate of impulse transmission through the accessory pathway and, thus, the ventricular rate.
If AFib were treated in the conventional manner by drugs that prolong the refractory period of the AV node (eg, calcium channel blockers, beta-blockers, digoxin), the rate of transmission through the accessory pathway likely would increase, with a corresponding increase in ventricular rate. This could have disastrous consequences, possibly causing the arrhythmia to deteriorate into V fib.
Procainamide (17 mg/kg IV infusion, not to exceed 50 mg/min; hold for hypotension or 50% QRS widening) blocks the accessory pathway, but it has the added effect of increasing transmission through the AV node.
Thus, although procainamide may control the AFib rate through the accessory pathway, it may create a potentially dangerous conventional AFib that may require treatment with other medications.
Prompt cardioversion of patients
with WPW and AFib is recommended.
Medical management may be a viable option in some patients, but it may have unpredictable results.
Note
that cardioversion is always the treatment of choice in
unstable patients."
From emedicine cited material originally authored by Mel Herbert, MD, MBBS, Assistant Professor of Medicine and Nursing, Department of Emergency Medicine, Olive View-University of California at Los Angeles Medical Center. This material has been subsequently updated; the new material is authored by Christopher Ellis, MD
Hondeghem, L.M. and Roden, D.M., "Agents Used in Cardiac Arrhythmias", in Basic and Clinical Pharmacology, Katzung, B.G., editor, Appleton & Lange, 1998, pp 216-241.
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