Antiarrhythmic Drugs Lecture

Introduction

• The heart's pumping action is controlled by its electrical system.
• Specialized cells create electrical impulses leading to cardiac muscle contraction.

Cardiac Conduction System

• Made up of 5 elements:
  1. Sinoatrial (SA) Node
  2. Atrioventricular (AV) Node
  3. Bundle of His
  4. Bundle Branches
  5. Purkinje Fibers
• Heart rhythm sequence explained via an electrocardiogram:
  • P wave: Atria contract
  • Line between P and Q wave: Delay at AV node
  • Q wave: Signal through Bundle of His
  • R and S waves: Ventricles contract
  • T wave: Ventricles recover

Cardiac Cells

• Contractile cells: Generate force for heart contraction.
• Conducting cells: Initiate electrical impulse (automaticity).
• Conducting cells found in SA node, AV node, Bundle of His, and Purkinje fibers.

Action Potential

Pacemaker Cells

• Main ions: Sodium, Calcium, Potassium
• Membrane potential changes create action potentials.
• Phases of action potential:
  • Phase 4: Slow depolarization
  • Phase 0: Rapid depolarization
  • Phase 3: Repolarization
• Excludes phase 1 and 2.

Cardiac Muscle Cells

• Phase 4: Resting membrane potential
• Phase 0: Sodium influx (rapid depolarization)
• Phase 1: Small dip due to potassium outflow
• Phase 2: Plateau (balanced ion exchange)
• Phase 3: Rapid repolarization

Arrhythmias

• Deviation from normal heart rhythm.
• Bradyarrhythmias: Heart rate below 60 BPM.
• Tachyarrhythmias: Heart rate above 100 BPM.
• Focus: Mechanisms of tachyarrhythmias:

Mechanisms:

1. Abnormal Automaticity: Increased slope of phase 4 depolarization.
2. Triggered Activity: Afterdepolarizations causing premature action potentials.
3. Reentry: Extra pathways causing abnormal loops (e.g., Wolff-Parkinson-White Syndrome, AVNRT).

Antiarrhythmic Drugs

Vaughan Williams Classification

• Class 1: Sodium channel blockers
  • Class 1A: Quinidine, Procainamide, Disopyramide
  • Class 1B: Lidocaine, Mexiletine
  • Class 1C: Flecainide, Propafenone
• Class 2: Beta-blockers (Propranolol, Metoprolol, Atenolol, Esmolol)
• Class 3: Potassium channel blockers
  • Amiodarone, Dronedarone, Sotalol, Dofetilide, Ibutilide
• Class 4: Calcium channel blockers (Verapamil, Diltiazem)
• Other Agents: Digoxin, Adenosine, Magnesium Sulfate

Drug Details

Class 1: Sodium Channel Blockers

• Class 1A: Moderate phase 0 depression; Prolonged action potential
  • Uses: Ventricular tachycardias, recurrent atrial fibrillation
  • Side Effects: Blurred vision, headache, anticholinergic effects
• Class 1B: Weak effect on phase 0; Shortened action potential
  • Uses: Ventricular arrhythmias
  • Side Effects: CNS toxicity (Lidocaine), Nausea/vomiting (Mexiletine)
• Class 1C: Marked phase 0 depression; Limited effect on repolarization
  • Uses: Refractory ventricular arrhythmias
  • Side Effects: Dizziness, blurred vision, nausea

Class 2: Beta-blockers

• Mechanism: Act on beta-1 receptors
  • Examples: Propranolol, Metoprolol, Atenolol, Esmolol
  • Uses: Arrhythmias due to sympathetic activity

Class 3: Potassium Channel Blockers

• Mechanism: Block potassium channels
  • Examples: Amiodarone, Dronedarone, Sotalol, Dofetilide, Ibutilide
  • Uses: Supraventricular/ventricular tachyarrhythmias, atrial fibrillation/flutter
  • Side Effects: Pulmonary fibrosis, thyroid dysfunction, neuropathy, hepatotoxicity

Class 4: Calcium Channel Blockers

• Mechanism: Block calcium channels
  • Examples: Verapamil, Diltiazem
  • Uses: Supraventricular tachycardia, atrial fibrillation

Other Agents

• Digoxin
  • Mechanism: Inhibits sodium-potassium pump leading to increased calcium
  • Uses: Heart failure + atrial fibrillation
• Adenosine
  • Mechanism: Stimulates A1 receptors; Decreases automaticity and conduction
  • Uses: Acute supraventricular tachycardia
  • Side Effects: Chest pain, flushing, hypotension
• Magnesium Sulfate
  • Mechanism: Role in ion transport across cell membranes
  • Uses: Torsades de pointes, Digoxin-induced arrhythmias