Antiarrhythmic agents are drugs used to suppress abnormal rhythms of the heart. They act to either:
- interfere with the dynamics of cardiac action potentials by blocking a certain ion channel,
or - block the
sympathetic effects of the autonomic nervous system on the heart, to slow down heart rate.
There are 5 classes of antiarrhythmic drugs: - Class I: Sodium-channel blockers: these drugs
bind to and block the fast sodium channels that are responsible for the depolarizing
phase in contractile myocytes. The result is a slower depolarization with a smaller amplitude.
Slower influx of sodium results in a smaller flow of positive ions through gap junctions to
adjacent cells; the adjacent cells take longer to reach the threshold required to generate a
new action potential, ultimately resulting in a slower propagation of action potentials through
the myocardium. This reduced conduction velocity helps to suppress formation of
re-entrant circuits, hence the use of these drugs for treating re-entrant tachycardias.
Class I agents are divided further into subclass IA, IB and IC. These subclasses differ in the
strength of sodium channel blockage, and in their effect on the duration of action
potentials and the effective refractory period, the ERP. While subclass IC has no effect on ERP,
IA prolongs and IB shortens ERP, respectively. Changes in ERP may have different outcomes for
different types of arrhythmias. A longer ERP generally reduces cardiac excitability,
but prolonged repolarizations may increase the risk of torsades de pointes, a type of
tachycardia caused by afterdepolarizations. - Class II: Beta-blockers: these drugs bind
to beta1-adrenergic receptors and block the sympathetic influences that act through these
receptors. Sympathetic nerves release catecholamines which act to increase
SA node firing rate and cardiac conductibility, especially at the AV node. These activities may
precipitate arrhythmias. Beta-blockers suppress sympathetic effects, thereby decreasing heart rate
and slowing down conduction through the AV node. The latter is particularly useful in treatment of
tachycardias that originate upstream of the AV node, known as supraventricular tachycardias,
or SVT. Note should be taken, however, that beta-blocker treatment may cause AV blocks.
- Class III: Potassium-channel blockers: these agents block the potassium channels
responsible for the repolarizing phase. The result is a slowed repolarization,
hence a prolonged duration of action potentials and refractory period. This reduces the heart’s
excitability and suppresses re-entrant tachycardias. However, these drugs may also
cause arrhythmias because slow repolarizations are associated with longer QT intervals and
increased risks of torsades de pointes. - Class IV: Calcium-channel blockers:
these drugs block calcium channels that are responsible for depolarization in SA and AV
nodal cells. Blocking these channels results in a lower sinus rate and slower conduction through the
AV node. However, because calcium is also involved in cardiac myocyte contraction, these agents also
reduce contractility of the heart and should not be used in case of systolic heart failures.
- Class V includes all drugs that act by other or unknown mechanisms.