Antiarrhythmic Drugs Lecture Notes

Introduction

• Topic: Antiarrhythmic Drugs
• Objective: Understand the mechanisms, applications, and key points about antiarrhythmic drugs.

Cardiac Physiology Refresher

• Myocardial Tissue Types: Key Points
  • Pacemaker Cells (Intrinsic Depolarization): SA node, AV node, bundle of His, bundle branches, Purkinje fibers.
  • Non-Pacemaker Cells (Dependent on External Stimuli): Atrial and ventricular myocytes.

Pacemaker Cells (SA and AV Nodes)

• Major Contributors: SA node (primary pacemaker), AV node, bundle of His, bundle branches, Purkinje fibers.
• Action Potential Phases: Key Points
  • Phase 4: Resting potential, slow depolarization through funny sodium (I_f) and T-type calcium (I_CaT) channels.
  • Phase 0: Rapid depolarization through L-type calcium (I_CaL) channels.
  • Phase 3: Repolarization via voltage-gated potassium (I_K) channels.

Non-Pacemaker Cells

• Resting Membrane Potential: Typically around -90 mV.
• Phases of Action Potential:
  • Phase 0: Rapid depolarization via voltage-gated sodium (I_Na) channels.
  • Phase 1: Initial repolarization through transient outward potassium (I_to) channels.
  • Phase 2: Plateau phase with balanced calcium influx (I_CaL) and potassium efflux (I_K).
  • Phase 3: Repolarization through delayed rectifier potassium (I_K) channels.
  • Phase 4: Resting potential maintenance through sodium-potassium ATPases.

Antiarrhythmic Drug Classes

1. Class I: Sodium Channel Blockers
2. Class II: Beta Blockers
3. Class III: Potassium Channel Blockers
4. Class IV: Calcium Channel Blockers
5. Miscellaneous (Class V): Includes adenosine, digoxin.

Detailed Mechanisms and Applications

Class I: Sodium Channel Blockers

• Subclasses (IA, IB, IC)
  • IA (Moderate Block): Disopyramide, Quinidine, Procainamide.
    • Increases QT interval (risk of torsades de pointes).
  • IB (Weak Block): Lidocaine.
    • Shortens action potential duration.
  • IC (Strong Block): Flecainide, Propafenone.
    • No change in QT interval duration but prolongs phase 0.

Class II: Beta Blockers

• Examples: Metoprolol, Atenolol, Propranolol.
• Mechanism: Inhibit beta-adrenergic effects, reducing conduction velocity, prolonging repolarization (phase 4).
• Applications: Rate control in AFib, AFlutter, SVT, VTach due to sympathetic overactivity.
• Adverse Effects: Bradycardia, AV block, hypotension, bronchospasm, hypoglycemia unawareness.

Class III: Potassium Channel Blockers

• Examples: Amiodarone, Dofetilide, Sotalol, Ibutilide, Dronedarone.
• Mechanism: Prolong depolarization; increase QT interval, prevent reentrant phenomena.
• Applications: Conversion and maintenance of sinus rhythm in AFib, AFlutter, Vtach.
• Adverse Effects: Risk of torsades de pointes, specific adverse effects for amiodarone (e.g., thyroid dysregulation, pulmonary fibrosis).

Class IV: Calcium Channel Blockers

• Examples: Verapamil, Diltiazem.
• Mechanism: Inhibit L-type calcium channels, reducing AV node conduction.
• Applications: Rate control in AFib, AFlutter, SVT.
• Adverse Effects: Bradycardia, AV block, hypotension, constipation.

Miscellaneous (Class V): Digoxin and Adenosine

• Digoxin: Increases vagal tone; used in AFib with heart failure.
• Adenosine: Short action in SVT by hyperpolarizing AV node.

Mechanisms of Arrhythmias

• Increased Automaticity: Increased SA/AV node activity.
• Triggered Activity: Early or delayed afterdepolarizations causing abnormal action potentials.
• Reentrant Circuits: Abnormal pathways causing rapid cyclical action potentials.

Strategy for Antiarrhythmic Therapy

• Rate Control (Primarily AV Node Suppression): Beta blockers, Calcium Channel Blockers, Digoxin.
• Rhythm Control (Suppress Ectopic/Triggered Activity): Sodium Channel Blockers, Potassium Channel Blockers.

Therapeutic Use and Adverse Effects

• AFib/AFlutter: Amiodarone, Beta blockers, Calcium Channel Blockers, Digoxin (with HF).
• SVT: Acute: Adenosine; Chronic: Beta blockers, Calcium Channel Blockers.
• VTach: Lidocaine (Post-MI), Amiodarone, Sotalol.
• Torsades de Pointes: Magnesium, Lidocaine.

Case Applications

• Post-MI Arrhythmias: Beta Blockers, Lidocaine.
• Coronary Artery Disease or Heart Failure: Avoid Type 1C agents like Flecainide.
• Persistent Arrhythmias: Combination of antiarrhythmic drugs and possible anticoagulation for clot prevention.

Conclusion

• Thorough understanding of antiarrhythmic drugs, their mechanisms, applications, and potential adverse effects is crucial for effective management of cardiac arrhythmias.