Class IC Antiarrhythmics

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Summary

Flecainide and propafenone belong to the Class IC antiarrhythmics. Just like the other class I antiarrhythmics, these drugs work by blocking sodium channels, prolonging the depolarizing upstroke in non-nodal cardiac tissue. Notably, Class IC drugs bind to the sodium channels tightly and dissociate slowly, giving them the highest use-dependence of the Class I drugs. Because they target sodium channels, these drugs work best in non-nodal tissue, meaning they are generally used for rhythm control of arrhythmias. However, flecainide and propafenone are also proarrhythmic and are contraindicated after an MI or in the presence of other structural or ischemic heart disease.

Key Points

  • Class 1C Antiarrhythmics
    • Drugs
      • Flecainide
      • Propafenone
      • Encainide
    • Mechanism
      • Block Sodium (Na+) channels
        • Prolong phase 0 depolarization in non-nodal cardiomyocytes (rhythm control)
          • Phase 0 upstroke is mediated by Ca2+ in nodal tissue, which is less affected by sodium channel blockade (less effective for rate control)
        • Strongest binding affinity (slowest dissociation) among Class 1 AAs
          • Binding affinity for Na+ receptor is 1C > 1A > 1B
          • Leads to strong use dependence
            • Use-dependence is a phenomena in which higher rates of depolarization (e.g. high HR) and long dissociation time (e.g. strong binding affinity) lead to accumulated blockade of sodium channel blockade (e.g. compounding effect over several cardiac cycles). This leads to slowing of conduction speed out of proportion to the prolongation of the refractory period.
            • Class 1C have strong binding and lengthy dissociation time, leading to rapid compounding and intensification over cycles; prolongs the QRS in a rate-dependent manner
      • Minimal effect on AP duration
        • Little effect on QT interval
    • Clinical Use
      • Supraventricular tachycardias
        • including atrial fibrillation
      • Used as a last resort in refractory VT
    • Adverse Effects
      • Proarrhythmic, especially post-MI
        • Contraindicated in structural and ischemic heart disease, especially post-myocardial infarction