Overview
This lecture reviews the drug class of calcium channel blockers, comparing non-dihydropyridines and dihydropyridines, focusing on their mechanisms, clinical uses, side effects, and drug interactions.
Calcium Channel Blocker Classification
- Calcium channel blockers are divided into non-dihydropyridines (diltiazem, verapamil) and dihydropyridines (e.g., amlodipine, nifedipine, nicardipine).
- Non-dihydropyridines are classified as Class IV antiarrhythmic agents (Vaughan Williams), while dihydropyridines are not antiarrhythmics.
- Dihydropyridines primarily act on vascular smooth muscle; non-dihydropyridines have significant cardiac effects.
Mechanisms of Action
- Non-dihydropyridines block calcium channels in SA and AV nodal cells, slowing phase 0 depolarization, causing negative chronotropic (rate), dromotropic (conduction), and inotropic (contractility) effects.
- Both classes reduce cytosolic calcium in smooth muscle and myocardium, leading to vasodilation and reduced cardiac contractility.
- No benefit in remodeling or mortality reduction in heart failure for calcium channel blockers, unlike beta blockers.
Hemodynamic and Vascular Effects
- Lower mean arterial pressure through decreased cardiac output and systemic vascular resistance.
- Dihydropyridines can cause reflex tachycardia due to vasodilation; non-dihydropyridines may prevent this.
- All classes reduce afterload; effective as antihypertensives, especially in populations less responsive to ACE inhibitors or ARBs.
Clinical Uses
- Non-dihydropyridines: hypertension, chronic stable and vasospastic angina, rate control in atrial fibrillation with RVR (not in WPW).
- Dihydropyridines: hypertension, angina, some used for coronary artery disease and hypertensive crises (e.g., IV clevidipine, nicardipine).
- Nimodipine is used only for subarachnoid hemorrhage, started within 96 hours and continued for 21 days.
Side Effects and Drug Interactions
- Non-dihydropyridines: bradycardia, AV block, caution in WPW, avoid in heart failure due to lack of remodeling benefit.
- All calcium channel blockers: constipation, lower extremity edema, gingival hyperplasia, potential GI bleeds, reflex tachycardia with dihydropyridines.
- Significant drug-drug interactions with diltiazem/verapamil (CYP3A4 and P-gp substrates/inhibitors).
Key Terms & Definitions
- Chronotropy — effect on heart rate.
- Dromotropy — effect on conduction velocity through the AV node.
- Inotropy — effect on the force of cardiac contraction.
- Reflex Tachycardia — compensatory increase in heart rate after vasodilation.
- WPW (Wolff-Parkinson-White) Syndrome — cardiac condition with accessory conduction pathway, contraindicating non-dihydropyridine use.
Action Items / Next Steps
- Review drug tables comparing agents, effects, and indications.
- Memorize key drug interactions, especially for diltiazem and verapamil.
- Read about clinical indications and contraindications for each subgroup.
- Be familiar with unique uses (e.g., nimodipine in subarachnoid hemorrhage, clevidipine in hypertensive crisis).