CJ

Antiarrhythmic Agents (Chapter 45)

Class 0: HCN Channel Blocker

  • Antiarrhythmic agents that affect the action potential by altering automaticity, conduction, or both.
  • Can be proarrhythmic (cause a new arrhythmia).
  • Classification overview:
    • Class 0: Affect HCN Channels (HCN blocker)
    • Example: ivabradine (Corlanor) discussed in Chapter 44.
    • Class I: Affect Sodium Channels
    • Class II: Affect autonomic receptors
    • Class III: Affect Potassium Channels
    • Class IV: Affect Calcium Channels

Class I Antiarrhythmics: Sodium Channel Blockers

  • Four subclasses:
    • Class Ia: disopyramide, procainamide, quinidine
    • Class Ib: lidocaine, mexiletine
    • Class Ic: flecainide, propafenone
    • Class Id: ranolazine (discussed in Chapter 46 for angina)
  • Mechanism of action:
    • Depress phase 0 of the action potential (AP).
    • Subclass specifics:
    • Ia: depress phase 0 and prolong duration of the action potential.
    • Ib: somewhat depress phase 0 and shorten duration of the AP.
    • Ic: markedly depress phase 0 with little effect on duration.
  • Clinical role:
    • These drugs are local anesthetics or membrane-stabilizers.
    • Used to treat potentially life-threatening ventricular arrhythmias.
  • Important notes:
    • Contraindications:
    • Bradycardia
    • Heart block (unless a pacemaker is present)
    • Hypotension or shock
    • Heart failure
    • Side effects/adverse effects:
    • CNS: dizziness, fatigue, slurred speech, etc.
    • GI: N/V, change in taste
    • Cardiovascular: proarrhythmic effects, respiratory depression, cardiac arrest
    • Drug interactions:
    • Quinidine with digoxin (increased risk for digoxin toxicity)
    • Class 1A serum levels may increase with cimetidine (gastric acid reducer)
    • Increased risk of bleeding if combined with warfarin
    • Specific drug cautions:
    • Quinidine: avoid foods that alkalinize urine (urine needs to be acidic for excretion). Foods include citrus juice, certain vegetables, antacids, milk products. Also avoid grapefruit juice due to metabolic interactions.

Class II Antiarrhythmics: Beta-Adrenergic Blockers and other ANS drugs

  • Drugs: acebutolol, esmolol, propranolol (beta-adrenergic blockers)
  • See foundational pharmacology (Chapter 31) for mechanism and broader uses; Digoxin can act as a muscarinic receptor agonist (Chapter 44); Muscarinic receptor inhibitors/anticholinergics include atropine (Chapter 33). Adenosine acts on adenosine receptors in the heart.
  • Uses:
    • Rapid atrial fibrillation (A-fib) and atrial flutter (A-flutter)
    • Paroxysmal supraventricular tachycardia (PSVT)
    • Hypertension (HTN)
    • Angina
    • Premature ventricular contractions (PVC)
    • Ventricular tachycardia (Vtach)
  • Actions:
    • Decreased heart rate (HR)
    • Decreased cardiac excitability
    • Decreased cardiac output (CO)
    • Slowing of AV node conduction
    • Decrease in renin release
  • Rationale: these effects reduce myocardial oxygen demand, suppress abnormal automaticity, and slow conduction through the AV node to control tachyarrhythmias.
  • Digoxin-specific notes (from this class):
    • Digoxin can act as a muscarinic receptor agonist, contributing to its effects on AV nodal conduction and conduction velocity.
  • Additional ANS agents:
    • Atropine (anticholinergic) as muscarinic receptor inhibitor
    • Adenosine (separate mechanism; see below)

Adenosine (Class II context: ANS-modulating agent for SVT)

  • Mechanism: activates adenosine receptors in the supraventricular tissue; effects sympathetic and parasympathetic inputs.
  • Uses: convert SVT to sinus rhythm (SR) when vagal maneuvers fail.
  • Dosing and administration (testable material):
    • Initial dose: 6\ \text{mg} IV bolus over 1\ ext{s}, followed by saline flush and immediate elevation of the arm.
    • If ineffective: 12\ \text{mg} bolus 1–2 minutes after initial dose, same technique.
    • May be repeated once with another 12\ \text{mg} dose for persistent PSVT.
  • Administration considerations:
    • Teach patient about the procedure beforehand.
    • Describe administration technique and that they may feel a sense of impending doom during treatment.
    • Continuous cardiac monitoring required.
    • A short period of asystole can follow administration (up to 15\ \text{s}).
  • Contraindications:
    • Tachycardia related to drug/poison
    • 2nd or 3rd degree heart block
  • Note: There is testable material here beyond generic pharmacology.

Class III Antiarrhythmics: Potassium Channel Blockers

  • Drugs: Amiodarone, Dofetilide, Dronedarone, Ibutilide, Sotalol
  • Uses:
    • Life-threatening ventricular arrhythmias
    • Amiodarone is used in the ACLS algorithm for ventricular arrhythmias
    • Maintenance of symptomatic A-fib or A-flutter
  • Key properties:
    • All drugs in this class are proarrhythmic in some settings.
  • Interactions and cautions:
    • There are several drug interactions (e.g., digoxin and quinidine can lead to toxicity).
    • Antihistamines can increase risk for proarrhythmia.
    • There are drug-specific interactions to consider with each agent.
  • General contraindications:
    • No contraindications when used to treat life-threatening ventricular arrhythmias if other drugs have not been effective; case-by-case assessment.
  • Amiodarone-specific notes:
    • Amiodarone is also a non-selective adrenergic blocking agent.
    • Side effects may reflect both potassium channel blockade and alpha/beta receptor blocking; include hypotension and bradycardia as common concerns.

Class IV Antiarrhythmics: Calcium Channel Blockers

  • Drugs: Diltiazem, Verapamil (non-dihydropyridines used for arrhythmias; dihydropyridines are more BP-focused)
  • Mechanism:
    • Block the movement of calcium across cardiac and smooth muscle membranes
    • Depression of generation of the action potential and delay of phases 1 and 2 of repolarization
    • Result: slows automaticity and slows conduction, particularly through the AV node
  • Uses:
    • Atrial fibrillation (A-fib)
    • Atrial flutter (A-flutter)
    • Paroxysmal supraventricular tachycardia (PSVT)
    • Also used for hypertension (HTN) and angina (as an antianginal/non-arrhythmia role) in other contexts
  • Side effects/adverse effects:
    • Decreased blood pressure (BP)
    • Negative inotropic effect (decreased force of contraction)
    • CNS effects: dizziness, fatigue, depression, headache
    • GI effects
  • Special notes:
    • In Chapter 43, calcium channel blockers for BP management include dihydropyridines; non-dihydropyridines are used for arrhythmias.
  • Magnesium sulfate note (not a Class IV drug):
    • Magnesium sulfate is sometimes referred to as a calcium channel blocker, but it is better described as a calcium channel antagonist that competes with calcium to reduce calcium influx.
    • Not discussed in this textbook page, but it is the treatment of choice for torsades de pointes (a specific ventricular tachycardia).
    • It is not considered a Class IV antiarrhythmic.