Lecture on Antiarrhythmic Drugs

Introduction

• Purpose: To provide an in-depth understanding of antiarrhythmic drugs.
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• Learning Enhancements: Use of illustrations and notes available on the website.

Overview of Antiarrhythmic Medications

• Antiarrhythmic drugs can be challenging due to their complexity and variations.
• Need for understanding cardiac physiology, action potentials, phases, channels, and ions.

Cardiac Physiology and Action Potentials

Myocardial Tissue Types

1. Pacemaker Cells (Nodal Cells):

   • SA Node: Located at the top of the right atrium - primary pacemaker.
   • AV Node: Conducts action potentials, backup pacemaker.
   • Conducting Pathway: SA Node → AV Node → Bundle of His → Bundle Branches → Purkinje Fibers.

2. Non-Pacemaker Cells (Atrial/Ventricular Myocytes):

   • Do not have intrinsic automaticity.
   • Depolarize through action potentials received via Gap Junctions.

Action Potentials in Pacemaker Cells

• Phases: Defined by specific channels and ion flows.
  • Phase 4: Funny Sodium Channels (I_f), bringing the cell to the threshold (pre-potential phase).
  • Phase 0: L-Type Calcium Channels, rapid depolarization.
  • Phase 3: Voltage-Gated Potassium Channels, repolarization.

Action Potentials in Non-Pacemaker Cells

• Phases: Differ from pacemaker cells.
  • Phase 0: Voltage-Gated Sodium Channels, rapid depolarization.
  • Phase 1: Initial repolarization (early efflux of potassium).
  • Phase 2: Plateau phase (influx of calcium and efflux of potassium).
  • Phase 3: Repolarization (efflux of potassium continues).
  • Phase 4: Resting potential maintained by sodium-potassium ATPases.

Arrhythmias Development Mechanism

Types of Arrhythmias

1. Increased Automaticity: Sinus tachycardia (increased SA node firing).
2. Triggered Activity:
   • Early afterdepolarizations (EADs): Prolonged QT intervals.
   • Delayed afterdepolarizations (DADs): Calcium overload.
3. Re-entrant Circuits: Anatomical (e.g., WPW) and functional (e.g., AVNRT, VTach).

Antiarrhythmic Drug Classes

Class I: Sodium Channel Blockers

• 1A Agents: Disopyramide, Quinidine, Procainamide.
  • Block Na⁺ and K⁺ channels, increase action potential duration.
• 1B Agents: Lidocaine, Mexiletine.
  • Block Na⁺ channels, shorten action potential duration.
• 1C Agents: Flecainide, Propafenone.
  • Strong Na⁺ channel blockade, no change in action potential duration.

Class II: Beta-Blockers

• Examples: Metoprolol, Propanolol, Esmolol.
• Mechanism: Blocks B₁ receptors, reducing heart rate.

Class III: Potassium Channel Blockers

• Examples: Amiodarone, Sotalol.
• Mechanism: Blocks K⁺ channels, prolongs repolarization.

Class IV: Calcium Channel Blockers

• Examples: Verapamil, Diltiazem.
• Mechanism: Blocks L-Type Ca²⁺ channels, slows heart's electrical properties.

Miscellaneous: Class V

• Examples: Adenosine, Digoxin.
• Mechanisms: Various; often work by affecting nodal tissues.
  • Adenosine: Blocks adenylate cyclase via G_i proteins; hyperpolarizes cells.
  • Digoxin: Enhances vagal tone, inhibits Na⁺/K⁺ ATPase.

Drug Utilization and Mechanisms

Indications

• Rate Control:
  • Use in tachyarrhythmias > 100 bpm.
  • Example drugs: Beta-blockers, Calcium channel blockers, Digoxin.
• Rhythm Control:
  • Converting abnormal rhythms back to normal (cardioversion).
  • Example drugs: Sodium channel blockers, Potassium channel blockers, Beta-blockers (in specific scenarios).

Treatment Approach by Condition

1. Atrial Fibrillation/Flutter:
   • Rate control: Beta-blockers, Calcium channel blockers.
   • Rhythm control: Amiodarone, Flecainide (watch for contraindications).
2. Supraventricular Tachycardia (SVT):
   • Acute treatment: Adenosine.
   • Prophylaxis: Beta-blockers, Calcium channel blockers.
3. Torsades de Pointes:
   • Immediate: Magnesium, Lidocaine (for QT interval reduction).

Adverse Drug Reactions

Class II Beta-Blockers

• Cardiac: Bradycardia, AV block, decreased contractility, hypotension (in HF).
• Non-Cardiac: Brochospasm (in asthma/COPD), hypoglycemia unawareness, worsening cocaine-induced hypertension.

Class IV Calcium Channel Blockers

• Cardiac: Bradycardia, AV block, decreased contractility, severe hypotension in CHF.
• GI: Constipation.

Miscellaneous: Adenosine and Digoxin

• Adenosine: Flushing, hypotension, chest pain, bronchospasm.
• Digoxin: GI disturbances, CNS effects, arrhythmias, hyperkalemia.

Class I Sodium Channel Blockers

• Class 1A: QT prolongation, anticholinergic effects (Disopyramide), cinchonism (Quinidine), drug-induced lupus (Procainamide).
• Class 1B: CNS effects, especially seizures (Lidocaine).
• Class 1C: Proarrhythmic effects in structural heart disease.

Class III Potassium Channel Blockers

• QT Prolongation: Risk of Torsades de Pointes.
• Amiodarone Specific: Thyroid dysfunction, pulmonary fibrosis, liver toxicity, skin discoloration.

Conclusion

• Understanding the mechanisms and appropriate uses of antiarrhythmic medications is crucial for managing cardiac arrhythmias effectively.
• Monitor for adverse effects based on specific drug classes and individual patient conditions.