(USMLE topics, cardiology) The 5 classes of agents according to Vaughan Williams classification, mechanism of action.
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ANTI-Arrhythmic 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 DE-polarizing phase in contractile myocytes. The result is a SLOWER depolarization with a smaller amplitude. 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. Useful in treatment of tachycardias that originate upstream of the AV node, known as supraventricular tachycardias, or SVT.
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 DE-polarization 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.
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