Cardiac Arrhythmias: Class I: sodium channel blockers

• block phase 0, i.e. blocks the sodium channels that cause fast depolarization

• this decreases the slope of phase 0

• suppress automaticity when automaticity depends upon sodium channels, so slows sinus rate

• repolarization

  • lengthened by group IA

  • shortened by group IB

  • no effect by group IC

• examples class IA

  • quinidine: class I effects at high doses, class III effects at all doses. side fx: QT prolongation and VT/VF, making this drug fall out of favor

  • procainamide: most useful in a setting of atrial fibrillation with rapid ventricular response due to an AV bypass tract (as in WPW). slows frequency of conduction through the accessory pathway. chronic use is limited by side effects including hypotension and drug-induced lupus

• examples class IB

  • lidocaine is used in the rx of VT and VF and is particularly effective in the setting of ischemia

  • effect is voltage-dependent, meaning that it is more active at reduced membrane potentials, which occur during ischemia

  • therapy limited by systemic toxicity, including CNS toxicity

• example class IC

  • flecainide is used in suppression of atrial fibrillation in patients with otherwise structurally normal hearts

  • test-question-type material: flecainide exhibits use dependence. this means that it has greater efficacy at faster heart rates. there is use-dependence-related widening of QRS complex

  • propafenone is similar, with additional class II (i.e., β-blocker) activity

• increased mortality in ventricular arrhythmias

  • in the past, class I drugs were commonly used to suppress ventricular arrhythmias in patients after MI

  • however, they increased mortality in this setting

Category: Pharmacology Notes