Antiarrhythmic Drugs

Cardiac Electrophysiology & Arrhythmia Basics - Shocking Rhythms

• Cardiac Action Potential (AP):
  • Phases: 0 (rapid $Na^+$ influx), 1 (early $K^+$ efflux), 2 (plateau: $Ca^{2+}$ influx, $K^+$ efflux), 3 (rapid $K^+$ efflux), 4 (resting potential).
  • Key Ions: $Na^+$, $Ca^{2+}$, $K^+$.
• Arrhythmias:
  • Types: Tachyarrhythmias (>100 bpm), Bradyarrhythmias (<60 bpm).
  • Origin: Supraventricular (atria/AV node), Ventricular.
• Antiarrhythmic Therapy Goals:
  • Control rate/rhythm.
  • Relieve symptoms, prevent complications (stroke, heart failure).

⭐ Key goals: Restore sinus rhythm or control ventricular rate; improve cardiac output, prevent complications (stroke, heart failure).

Class I Antiarrhythmics ($Na^+$ Blockers) - Salty Channel Tamers

• Vaughan Williams Class I: $Na^+$ channel blockers; state-dependent (act on open/inactivated channels).

• Class IA: "Queen Proclaims Diso's pyramid"
• Class IB: "Lidocaine Mexes with Pheny"
• Class IC: "Flecainide Propafenone for life" (but be careful!)

⭐ Class IC antiarrhythmics (e.g., Flecainide) are contraindicated in structural heart disease or post-MI due to ↑mortality (CAST trial).

Class II Antiarrhythmics (β-Blockers) - Beta Beat Controllers

• Vaughan Williams Class II: β-adrenergic blockers.
• Mechanism: ↓cAMP, ↓$Ca^{2+}$ currents; primarily slow SA & AV nodal conduction, ↓slope of phase 4 depolarization.
• Key Drugs: Propranolol, Metoprolol, Esmolol (short-acting).
• Clinical Uses: Rate control in atrial fibrillation/flutter, SVTs, ↓ventricular ectopy, post-MI protection.
• Key Side Effects: Bradycardia, AV block, bronchospasm (non-selective), fatigue.

⭐ Beta-blockers are unique among antiarrhythmics for their proven mortality benefit in post-myocardial infarction patients.

Class III Antiarrhythmics ($K^+$ Blockers) - Potassium's Power Play

• Vaughan Williams Class III: $K^+$ channel blockers.
• Mechanism: Prolong repolarization (Phase 3), ↑Action Potential Duration (APD), ↑Effective Refractory Period (ERP).
  • ⚠️ Risk: Torsades de Pointes (TdP).
• Key Drugs:
  • Amiodarone: Multi-channel effects; broad spectrum, complex PK.
  • Sotalol: Also β-blocker; dose-dependent TdP risk.
  • Dofetilide, Ibutilide.
• Amiodarone Side Effects: 📌 P-F-T-L-C-S (Pulmonary fibrosis, Eyes-corneal microdeposits, Thyroid/Testes dysfunction, Liver toxicity, CNS effects, Skin discoloration).

⭐ Amiodarone is notorious for its extensive drug interactions, primarily due to its inhibition of CYP450 enzymes (e.g., CYP3A4, CYP2C9) and P-glycoprotein.

Class IV Antiarrhythmics ($Ca^{2+}$ Blockers) - Calcium's Calming Crew

• Class: Non-DHP $Ca^{2+}$ blockers (L-type).
• Action: ↓SA/AV conduction (↓$phase 0$ nodal).
• Drugs: Verapamil, Diltiazem.
• Uses: AF/AFL rate control, PSVT.
• SEs: Bradycardia, AV block, constipation, edema. ⚠️ HF.
• CIs: WPW + AF, severe LV dysfunction.

⭐ Calcium channel blockers like Verapamil and Diltiazem are contraindicated in patients with Wolff-Parkinson-White (WPW) syndrome and atrial fibrillation as they can paradoxically increase ventricular rate by blocking AV nodal conduction and promoting conduction via the accessory pathway.

Miscellaneous Antiarrhythmics - The Unique Beats

📌 Adenosine: 'A-DEN-O-SINE' (Almost Dead, ENd Of SVT, Short-acting, IV, No effect on VT, EKG flatline).

⭐ Adenosine is highly effective for terminating paroxysmal supraventricular tachycardias (PSVTs) involving the AV node, but it is ineffective for atrial fibrillation, atrial flutter, or ventricular tachycardia.

High‑Yield Points - ⚡ Biggest Takeaways

• Vaughan Williams classification (I-IV) is key: Na+, β-blockers, K+, Ca2+ blockers.
• Amiodarone (Class III): broad-spectrum but major toxicities (pulmonary, thyroid, corneal).
• Adenosine: terminates acute SVT; very short half-life, transient asystole.
• Lidocaine (Ib): for ventricular arrhythmias post-MI, especially ischemia-related.
• Class Ic (Flecainide, Propafenone): avoid in structural heart disease (CAST trial risk).
• Beta-blockers (II): crucial for rate control in AFib & post-MI survival.