antiarrythmia
TRANSCRIPT
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CARDIAC ARRHYTHMIA
Stacy Arvinna J,Group 3KSMU
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• 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
TOPICS COVERED
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MECHANISMS OF CARDIAC ARRHYTHMIAS
1. Enhancement or depression of impulse generation a. 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 tissue peri AV nodal or Purkinje system. due to I.early. afterdepolarizations II.late"af'èé1^depolarízations
2. Abnormal conduction of the cardiac impulse a. Conduction block b. Delayed conduction c. Unídirectional block and reentry or reflection
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VENTRICULAR RE-ENTRY
•Abnormal pattern of depolarization through the heart
•Functional•Anatomic
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THE CARDIAC ACTION POTENTIAL
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ION CHANNELS RELEVENT TO THE CARDIAC ACTION
POTENTIAL
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Antiarrhythmic Drug Pathways
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THE VAUGHAN WILLIAMS CLASSIFICATION SYSTEM OF ANTI-ARRHYTHMIC DRUGS
Class Basic MechanismI-Sodium Channel Blockade
Reduce phase 0 slope and peak of action potential
IA Moderate reduction in phase 0 slope; increase APD; increase ERP
IB Small reduction in phase 0 slope; reduce APD; decrease ERP
IC Pronounced reduction in phase 0 slope; no effect on APD or ERP
II-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 0
IV-Calcium channel blockade
Block L-type calcium-channels; most effective at SA and AV nodes; reduce rate and conduction.
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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
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CLASS I• IA
– moderate
• IB– weakest
• IC– strongest
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CLASS IA
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CLASS IA-Procainamide
Procainamide
N-Acetyl Procainamide
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CLASS IB
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CLASS IB-Lidocaine
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CLASS IC
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CLASS IC-flecainide
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Cardiac Side Effects-Proarrhythmia
•Potential re-entrant circuit can be turned into an actual re-entrant circuit
• Increased incidence of death in the case of myocardial infarction
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Class III
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CLASS III-Sotalol
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Torsades des Pointes
•Long Q-T syndrome•Polymorhic Ventricular Tachycardia•IA drugs can also cause this
•Blocking of potassium channels and prolonging repolarization
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ALTERNATIVE TREATMENTS
• Ablation• Implanantable
Cardioverter Defibrillators (ICDs)
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ICD Placement In the Heart
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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?
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Antiarrhythmic Drug Pathways
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• :www.aavpt.org/symposia/documents/Muir213-221.pdf