Class IV antiarrhythmics (calcium channel blockers)

Mechanism of Action - Closing the Calcium Gates

• Primary Target: Block voltage-gated L-type calcium channels ($Ca_V 1.2$), primarily in cardiac tissue.
• Key Sites of Action: Greatest effect on the sinoatrial (SA) and atrioventricular (AV) nodes, which are calcium-dependent.
• Electrophysiological Effects:
  • Decreases the inward calcium current ($I_{Ca}$) that drives the late Phase 0 depolarization in nodal cells.
  • Slows the rate of rise of the SA node pacemaker potential → ↓ heart rate (negative chronotropy).
  • Slows conduction velocity and increases the effective refractory period (ERP) in the AV node.

⭐ By slowing AV conduction, Class IV drugs characteristically prolong the PR interval on an ECG. This is their primary antiarrhythmic mechanism for controlling ventricular rate in atrial fibrillation.

Types & Pharmacokinetics - Dihydros vs. Non-dihydros

• Dihydropyridines (DHPs): Amlodipine, Nifedipine ("-dipine" suffix)

  • Vascular-selective: Potent arteriolar vasodilation with minimal effect on cardiac contractility or AV node conduction at therapeutic doses.
  • Used for hypertension and angina.
  • 📌 Mnemonic: "Di-hydro-Pines" primarily "Di-late" peripheral vessels.

• Non-dihydropyridines (Non-DHPs): Verapamil, Diltiazem

  • Cardio-selective: Act on both the heart and vascular smooth muscle, decreasing cardiac workload.
  • Verapamil: Most cardioselective; significant negative inotropic and chronotropic effects. Think Verapamil for Ventricular rate control.
  • Diltiazem: Intermediate action on both heart and vessels.
  • Used for rate control (atrial fibrillation/flutter) and angina.

⭐ Dihydropyridines can trigger reflex tachycardia due to profound vasodilation and baroreceptor activation. This is counteracted by Non-DHPs, which directly suppress heart rate.

Clinical Applications - The Heart Rescuers

• Supraventricular Tachycardias (SVT): Excellent for terminating re-entrant tachycardias that depend on the AV node for the circuit.
• Atrial Fibrillation & Flutter: A cornerstone of therapy for rate control by directly slowing AV nodal conduction.
• Angina Pectoris (Stable & Vasospastic): Decrease myocardial oxygen demand by reducing heart rate, contractility, and afterload.
• Hypertension: Effective, particularly in patients with comorbid angina or arrhythmias.
• Migraine Prophylaxis: Verapamil is used for prevention.

⭐ In hypertrophic cardiomyopathy (HCM), non-dihydropyridine CCBs are used to improve diastolic relaxation and reduce symptoms related to dynamic outflow tract obstruction.

Adverse Effects & Contraindications - Handle With Care

• Cardiovascular System:
  • Bradycardia, high-degree AV block, and worsening heart failure (especially non-dihydropyridines like Verapamil).
  • Peripheral edema, flushing, headache, and dizziness (more common with dihydropyridines).
  • Symptomatic hypotension.
• Other Key Effects:
  • Constipation is a classic side effect of Verapamil. 📌 Verapamil = Very constipating.
  • Gingival hyperplasia can occur with prolonged use.
• Contraindications & Cautions:
  • ⚠️ Sick Sinus Syndrome or 2nd/3rd degree AV block without a functioning pacemaker.
  • Severe hypotension (Systolic BP < 90 mmHg).
  • Decompensated heart failure.
  • ⚠️ Avoid concurrent IV non-DHPs with IV β-blockers.

⭐ In Wolff-Parkinson-White (WPW) syndrome, giving a CCB during atrial fibrillation blocks the normal AV node pathway. This forces impulses down the faster accessory pathway, potentially triggering ventricular fibrillation.

High‑Yield Points - ⚡ Biggest Takeaways

• Verapamil and diltiazem primarily block L-type Ca²⁺ channels in cardiac tissue.
• Their main effect is to slow conduction through the AV node, reducing heart rate.
• Clinically used for rate control in atrial fibrillation and other supraventricular tachycardias.
• Key side effects include constipation (especially verapamil), gingival hyperplasia, and bradycardia.
• Avoid use in systolic heart failure and in patients with 2nd or 3rd-degree AV block.