Updates on antiarrhythmic drugs

Updates on antiarrhythmic drugs Dr TEO Wee Siong MBBS (S’pore), M Med (Int Med), FAMS, MRCP (UK), FRCP (Edin), FACC, FHRS President, APHRS Mt Elizabeth Hospital, Singapore Senior Advisor, Electrophysiology & Pacing Department of Cardiology National Heart Centre, Singapore Antiarrhythmic Therapy  General Medical measures   electrolytes, sedation, acid base Pharmacotherapy Anti-arrhythmic drugs  Drug treatment of etiologic factors – upstream therapy   Electrical and Device therapy   Surgery   cardioversion, pacing, defibrillation antiarrhythmic surgery, revascularization Catheter Ablation Rapid repolarization Plateau Depolarization Resting potential Basic Cellular Electrophysiology Final repolarization Spontaneous depolarization Basic Mechanism of Arrhythmias Classification of antiarrhythmic drugs   Vaughan Williams Classification Sicilian Gambit  channel blocking, receptor activation and ionic pump The Vaughan William’s Classification of AAD is based on their effects on the cardiac action potential (AP) Vaughn-Williams Classification of Antiarrhythmic Drug Actions Class I Action Sodium Channel Blockade II III Beta Blockade Potassium Channel Blockade IV Calcium Channel Blockade Drug IA: Disopyramide Quinidine Procainamide IB: Lidocaine Mexiletine IC: Flecainide Propafenone Beta Blockers Amiodarone Sotalol Calcium Channel Blockers Cellular basis for action of antiarrhythmic drugs Class antiarrhythmic drugs   Membrane stabilizers Main site of action blocks membrane Na channels  inhibits fast inward Na current   Results in     reduction in velocity of action potential upstroke (phase 0) decrease in the max amplitude achieved (phase 1) prolong phase repolarization of the action potential or the refractory period reduces conductivity, excitability and automaticity Procainamide   Type IA antiarrhythmic Iv or oral  Acute Intravenous 20 mg/min until arrhythmia controlled or total of gm given or acute side effects (eg hypotension) occurs (10-20 mg/kg)  Continuous infusion 2-4 mg/min (20-80 mcg/kg/min) Oral Procainamide durules gm tds    Indicated for acute conversion of WCT, VT, preexcited AF Side effects     Hypotension Gastrointestinal – nausea, diarrhoea Drug induce SLE (allergic skin rash, arthralgia) Proarrhythmia – can result in incessant VT Connolly S Dronedarone – Adverse reactions       No significant thyroid side effects Little if any pulmonary fibrosis GI irritation Liver toxicity Prolongs QT interval Negative inotrope  Contraindicated in HF pts Ranolazine     Ranolazine is a drug that exerts antianginal and antiischemic effects without impacting heart rate or bp At therapeutic levels, ranolazine inhibits the late phase of the inward sodium channel (late INa) in ischemic cardiac myocytes, reducing intracellular sodium concentrations This channel inhibition results in a reduction in calcium influx via Na+-Ca2+ exchange, translating into decreased oxygen consumption At higher concentrations, ranolazine inhibits the rapid delayed rectifier potassium current (IKr) thus increasing the ventricular action potential duration and prolonging the QT interval For atrial arrhythmias, ranolazine is synergistic with Dronedarone and further suppresses AF without increasing proarrhythmia hazard Ranolazine -Primary arrhythmia end points MERLIN TIMI 36 Arrhythmic end point Ranolazine (%) Placebo (%) p Ventricular tachycardia >3 beats 52.0 60.6 8 beats 5.3 8.3 beats 44.7 55.0