ANTIARRHYTHMIC DRUGS

Mark Tuttle 2017

SINGH-VAUGHAN-WILLIAMS CLASSIFICATION​1  ● Criticism: Antiarrhythmics are "dirty" drugs, have effects in multiple categories or have metabolites which do ● Sicilian Gambit​4​ sought to redefine this classification with more targeted mechanisms, but was not widely adopted. ○ Paper contains excellent chart (Figure 7) of drugs’ affinities to various receptors. ● Class I​: Na channel blocker, ○ Potency of blockade: Ic > Ib > Ia ○ Use-dependency Ic > Ia > Ib ○ CAST trial​2​: gave patients class I drugs if they had PVCs post-MI and they died more frequently than without the drug, led to paradigm shift discouraging the use of these drugs. ○ Ia​: Reduce Vmax of phase 0 and prolong action potential duration (APD) ■ Procainamide ■ Quinidine ■ Dysopyramide ○ Ib​: Does not reduce Vmax and shortens action potential duration (APD) ■ Lidocaine (IV) ■ Mexiletine (PO) ■ Phenytoin ○ Ic​: Reduce Vmax, slow conduction velocity, prolong refractoriness minimally Primarily for atrial arrhythmias, like AF (lone AF without structural heart disease only) ■ Flecainide ■ Propafenone ● Class II​: B-blockers ● Class III​: K-channel blockers, prolong repolarization and thus refractory period ○ Amiodarone ■ VT: Helpful in acute setting, but no benefit to chronic therapy. ● SCD-HeFT​5​ : Amiodarone versus placebo arm (28% vs. 29% mortality, p=0.53). Not significant. ■ AF: ○ Dofetelide (PO): AF (CHF, CAD okay) ○ Ibutilide (IV) ○ Sotalol: AF (Avoid in depressed LVEF since there is an increase in mortality [SWORD trial​3​]) ○ Dronaderone: Do not use in CAD, CHF ● Class IV​: Calcium channel blockers ● Digoxin ○ ↑ vagal tone ○ ↑ inotropy ○ Dig "effects": bradycardia, ST scooping, AT shortening (local hyperCa2+), U waves ○ Dig "toxicity": vision changes, N/V, abdominal pain, heart block, atrial tachycardia, bidirectional VT

ANTIARRHYTHMIC DRUGS

Mark Tuttle 2017

Froum source #4

SOURCES  1. Vaughan williams EM. The experimental basis for the choice of an anti-arrhythmic drug. Adv Cardiol. 1970;4:275-89. 2. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324(12):781-8. 3. Waldo AL, Camm AJ, Deruyter H, et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction

after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet. 1996;348(9019):7-12. 4. The 'Sicilian Gambit'. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. The Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Eur Heart J. 1991;12(10):1112-31. 5. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225-37.