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2. Anti-dysrhythmic Drugs

Anti-dysrhythmic Drugs Overview

  • Presented by Dr. Declan McKernan

  • Contact: declan.mckernan@universityofgalway.ie

  • Course: PM309 Cardiovascular Drugs

Learning Outcomes

  • Describe targets and mechanisms of action of major classes of anti-dysrhythmic drugs with named examples.

  • Compare and contrast mechanisms of action, pharmacokinetics, and side effects of these drugs with named examples.

Mechanisms of Action of Anti-dysrhythmic Drugs

Visual Summary

  • Action Potential Patterns:

    • Lengthened, shortened, and unchanged potentials observed with various drug actions.

Classification of Antiarrhythmic Drugs

Table 1: Antiarrhythmic Drug Classification

Class

Effect

Membrane Effect

Examples

IA

QRS and Q-T interval

Sodium & Potassium channel block

Quinidine, Procainamide, Disopyramide

IB

Q-T interval

Sodium channel block

Lidocaine, Mexiletine

IC

QRS interval

Sodium channel block

Flecainide, Propafenone

II

Heart rate; P-R interval

Beta-adrenergic receptor inhibition

Propranolol

III

Q-T interval

Potassium channel block

Amiodarone, Sotalol

IV

Heart rate; P-R interval

Calcium channel block

Verapamil, Diltiazem

Other

P-R interval; Q-T inhibition

Na+, K+-ATPase inhibition

Digoxin, Adenosine

Targets of Anti-dysrhythmic Drugs

  • Class I examples: Flecainide (Na+ blocker)

  • Class II examples: Propranolol (b-receptor antagonist)

  • Class III examples: D-sotalol (K+ blocker)

  • Class IV examples: Verapamil (Ca+ blocker)

Specific Indications for Antiarrhythmic Drugs

Table 2: Drug Indications

  • Sinus Tachycardia: Propranolol

  • Sinoatrial Reentrant Tachycardia: Verapamil

  • AV Nodal Reentrant Tachycardia: IV Verapamil, IV Diltiazem

  • Atrial Fibrillation: IV Procainamide, IV Ibutilide

  • Ventricular Tachycardia: Lidocaine, IV Procainamide

Class-Specific Drug Mechanisms

Class I Drugs

  • Mechanism of Action: Block voltage-sensitive Na+ channels.

  • Effects: Decreased automaticity and upstroke velocity, prolonged effective refractory period.

Class IA Drugs

  • Mechanism: Moderate block on open Na+ channels; also blocks K+ channels.

  • Examples: Quinidine, Procainamide, Disopyramide.

  • Side Effects: Diarrhea, nausea, drug interactions (e.g., digoxin).

Class IB Drugs

  • Mechanism: Bind to open/inactivated Na+ channels, mild block.

  • Examples: Lidocaine, Mexiletine.

  • Clinical Use: Emergencies for ventricular arrhythmias only; safe in prolonged QT syndrome.

Class IC Drugs

  • Mechanism: Most potent Na+ channel blockers.

  • Risk: Can worsen existing arrhythmias; used only in life-threatening situations.

Class II Drugs

  • Mechanism: B-adrenergic receptor blockade; decreases sympathetic influence on SA and AV nodes.

  • Examples: Propranolol, Atenolol.

  • Clinical Uses: Tachycardias induced by physical/emotional stress.

Class III Drugs

  • Mechanism: Block K+ channels, prolong plateau, and repolarization.

  • Example: Amiodarone (also has Class I, II, IV activities).

Class IV Drugs

  • Mechanism: Block Ca2+ channels in nodal tissues to decrease conduction velocity.

  • Examples: Verapamil, Diltiazem.

Pharmacokinetics of Antiarrhythmic Drugs

Table 4: Summary of Pharmacokinetic Properties

  • Notable Drugs:

    • Amiodarone: 200-400 mg daily; hepatic metabolism; long half-life (~53 days).

    • Digoxin: 0.25 mg; renal elimination; 20-30% bioavailability.

Summary of Drug Classes

  • Class I: Block Na+ channels; decrease automaticity and arrhythmia risk.

  • Class II: Inhibit sympathetic input at pacemaker cells.

  • Class III: Prolong repolarization by blocking K+ channels.

  • Class IV: Block Ca2+ channels, impacting conduction in nodal tissues.