Antiarrhythmic classification and mechanisms

Cardiac Action Potential - The Heart's Electrical Dance

• Non-pacemaker (Ventricular/Atrial): Fast response, stable Phase 4.
• Pacemaker (SA/AV nodes): Slow response, unstable Phase 4 (funny current, $I_f$)

⭐ The slope of Phase 4 in pacemaker cells determines the heart rate. Steeper slope = faster heart rate.

Class I Agents - Salty Blockade Crew

• Mechanism: State-dependent Na⁺ channel blockade, slowing the phase 0 upstroke. This decreases conduction velocity in non-nodal tissue.
• Subclasses are based on the strength of blockade and effect on action potential duration (APD).
  • IA (e.g., Quinidine, Procainamide): Moderate blockade; ↑ APD.
  • IB (e.g., Lidocaine, Mexiletine): Weak blockade; ↓ APD. Targets ischemic tissue.
  • IC (e.g., Flecainide, Propafenone): Strong blockade; no change in APD.

📌 Mnemonic: "Queen Proclaims Diso's pyramid" (IA), "Lettuce & Mayo" (IB), "Fries Please" (IC).

⭐ Use-Dependence: Blockade intensifies with faster heart rates. Class IC has the strongest use-dependence and is contraindicated post-MI due to increased mortality from proarrhythmia.

Class II Agents - Beta Block Party

• Mechanism: Primarily act on nodal tissue by blocking β-adrenergic receptors. This ↓ cAMP, leading to ↓ Ca²⁺ currents.
  • Slows phase 4 diastolic depolarization (pacemaker potential).
  • Increases PR interval.
• Agents: Metoprolol, Labetalol, Propranolol, Esmolol (short-acting).
• Use: Rate control (atrial fibrillation/flutter), post-MI, thyrotoxicosis.

⭐ Esmolol's very short half-life makes it ideal for critically ill patients or when short-term β-blockade is desired.

Class III Agents - K+ Channel Kickers

• Mechanism: Block delayed rectifier K+ channels ($I_K$).
• Effect: Prolong action potential duration (APD) & effective refractory period (ERP).
• EKG: ↑ QT interval.
• Agents: Amiodarone, Ibutilide, Dofetilide, Sotalol (📌 AIDS).
• Toxicity: Risk of Torsades de Pointes (TdP) due to QT prolongation.

⭐ Amiodarone uniquely exhibits effects of all four antiarrhythmic classes. Monitor for its classic pulmonary fibrosis, hepatotoxicity, and thyroid dysfunction (hypo/hyper).

Class IV Agents - Calcium Channel Chillers

• Mechanism: Block voltage-gated L-type Ca²⁺ channels, primarily affecting SA and AV nodes.
• Effect: Slows phase 4 spontaneous depolarization and phase 0 upstroke. This leads to ↓ heart rate and ↓ conduction velocity.
• EKG: ↑ PR interval.
• Agents: Verapamil, Diltiazem.

⭐ Use-dependence: These drugs show greater effect at faster heart rates, as they bind more effectively to open or inactivated Ca²⁺ channels.

Other Agents - The Odd Squad

• Adenosine: Activates A1 receptors → ↑ K+ out, ↓ Ca2+ in → hyperpolarizes AV node. Terminates SVT. Effects blunted by caffeine/theophylline.
• Magnesium ($Mg^{2+}$): Blocks influx through L-type Ca2+ channels. Drug of choice for Torsades de Pointes.
• Ivabradine: Inhibits funny current ($I_f$) in SA node.

⭐ Adenosine causes transient asystole for diagnostics and can provoke bronchospasm in asthmatics.

High‑Yield Points - ⚡ Biggest Takeaways

• Class I drugs exhibit use-dependence, preferentially targeting channels in rapidly depolarizing tissue.
• Class II (β-blockers) and Class IV (Ca²⁺ blockers) primarily slow conduction through the AV node, increasing the PR interval.
• Class III K⁺ blockers prolong the action potential, which increases the QT interval and the risk of Torsades de Pointes.
• Amiodarone has properties of all four classes and carries significant pulmonary and thyroid toxicity.
• Adenosine is extremely short-acting, used to terminate supraventricular tachycardias.
• Digoxin increases vagal tone to slow AV conduction in atrial fibrillation.