TOPICS COVERED• Types of Arrhythmias – Ventricular• Cardiac Action Potential• Ion Channels of Interest• Classification of Anti-arrhythmic drugs• Drugs and Re-entry• Class I Drugs• Class III Drugs• Side Effects• Alternative Treatments and Future Drug Development
MECHANISMS OF CARDIAC ARRHYTHMIAS1. Enhancement or depression of impulse generationa. Enhanced or depressed normal automaticity from the SA node,b. Abnormal automaticity develop in atrial or ventricular myocardium.c. Triggered activity develop from normally quiescent cardiac tissueperi AV nodal or Purkinje system. due toI.early. afterdepolarizationsII.late"afèé1^depolarízations2. Abnormal conduction of the cardiac impulsea. Conduction blockb. Delayed conductionc. Unídirectional block and reentry or reflection
VENTRICULAR RE-ENTRY •Abnormal pattern of depolarization through the heart •Functional •Anatomic
THE VAUGHAN WILLIAMS CLASSIFICATION SYSTEM OF ANTI- ARRHYTHMIC DRUGSClass Basic MechanismI-Sodium Channel Blockade Reduce phase 0 slope and peak of action potentialIA Moderate reduction in phase 0 slope; increase APD; increase ERPIB Small reduction in phase 0 slope; reduce APD; decrease ERPIC Pronounced reduction in phase 0 slope; no effect on APD or ERPII-Beta-blockade Delay repolarization (phase 3) and thereby increase action potential duration and effective refractory period.III-potassium-channel blockade Prolongation of APD and increase ERP; no effect on phase 0IV-Calcium channel blockade Block L-type calcium-channels; most effective at SA and AV nodes; reduce rate and conduction.
HOW THESE DRUGS AFFECT RE-ENTRY • Class I: retards conduction enough so that beat still gets through normal cardiac tissue but not through any weakened tissue • Class III: prolongs refractoriness
CLASS I• IA – moderate• IB – weakest• IC – strongest
FUTURE OF DRUG DEVELOPMENT• Drugs with defibrillating effects – Sotalol – Tedisamil • Sympathomimetic-modulates cAMP • Protects Gap junctions and enhances Ca2+ uptake by SR• Drugs affecting Ion Channelopathy – hyperphosphorylation• Drugs or Devices?