Calcium Channel Blockers
Calcium channel blockers inhibit L-type calcium channels in cardiac and vascular smooth muscle. The dihydropyridine and non-dihydropyridine subclasses have distinct clinical profiles.
## Mechanism of Action
Calcium channel blockers (CCBs) inhibit voltage-gated L-type calcium channels, reducing intracellular calcium influx. In vascular smooth muscle, this causes relaxation and vasodilation. In cardiac tissue, it reduces contractility, heart rate, and conduction velocity through the AV node. The relative selectivity for vascular vs cardiac tissue defines the two main subclasses.
## Dihydropyridines
Amlodipine, nifedipine, felodipine, and lercanidipine are primarily vascular selective. They cause potent arterial vasodilation with minimal direct cardiac effects at therapeutic doses.
- **Uses:** Hypertension (first-line), Raynaud's phenomenon, stable angina.
- **Side effects:** Peripheral edema (dose-dependent, due to precapillary dilation), flushing, headache, reflex tachycardia (more with short-acting nifedipine).
- **Amlodipine** has a long half-life (~40 hours), allowing once-daily dosing and smooth blood pressure control.
## Non-Dihydropyridines
Verapamil and diltiazem have significant effects on both the vasculature and the heart.
- **Verapamil** -- Strongest negative inotropic and chronotropic effects. Used for rate control in atrial fibrillation, supraventricular tachycardia, and hypertension. Constipation is a common and dose-limiting side effect.
- **Diltiazem** -- Intermediate profile between dihydropyridines and verapamil. Effective for rate control and angina. Fewer GI side effects than verapamil.
## Critical Drug Interactions
Non-dihydropyridines combined with beta-blockers can cause severe bradycardia, AV block, or heart failure due to additive negative chronotropic and inotropic effects. This combination requires close monitoring and is generally avoided in patients with pre-existing conduction abnormalities.
Verapamil and diltiazem inhibit CYP3A4 and P-glycoprotein, increasing levels of statins (especially simvastatin), cyclosporine, digoxin, and many other drugs. Dose adjustments are frequently required.
## Clinical Pearls
- Amlodipine is one of the few antihypertensives safe in pregnancy for chronic hypertension management (though labetalol and nifedipine are preferred).
- Nifedipine extended-release (not immediate-release) is used for hypertension. Short-acting nifedipine capsules caused reflex tachycardia and were linked to adverse cardiac events.
- CCBs do not worsen lipid profiles or glucose tolerance, making them metabolically neutral options for hypertension.
## Key Takeaways
- Dihydropyridines are vascular-selective; non-dihydropyridines also affect the heart.
- Amlodipine is the most prescribed CCB due to its long half-life and smooth efficacy.
- Never combine non-dihydropyridine CCBs with beta-blockers without careful monitoring.
- CCBs are particularly useful when beta-blockers or RAAS inhibitors are contraindicated.