Cardiovascular · Medicine Class

Calcium Channel Blockers (CCBs)

Blockade of L-type voltage-gated calcium channels

Mechanism of Action

Calcium channel blockers block L-type (long-acting) voltage-gated calcium channels in vascular smooth muscle and cardiac cells. In vascular smooth muscle, calcium influx is required for contraction — blockade produces vasodilation. In cardiac cells, calcium influx drives the action potential plateau phase and mediates myocardial contractility and SA/AV node conduction. Dihydropyridines (DHPs) preferentially affect vascular smooth muscle with minimal cardiac effects at standard doses. Non-DHPs (diltiazem, verapamil) have equal cardiac and vascular effects.

Therapeutic Indications

Hypertension — first-line, all subtypes
Stable angina — reduce cardiac oxygen demand and coronary spasm
Vasospastic (Prinzmetal) angina
Atrial fibrillation rate control — non-DHPs only
Supraventricular tachycardia (SVT) — verapamil/diltiazem
Raynaud's phenomenon — nifedipine
Migraine prevention (verapamil)

Medicines in This Class

Amlodipine (Norvasc)

DHP; most prescribed CCB; once daily; very long half-life (30-50h); minimal reflex tachycardia. First-line in hypertension.

Nifedipine (Adalat, Procardia)

DHP; IR formulation causes reflex tachycardia and headache; XL/GITS preferred. Used in Raynaud's, hypertensive urgency.

Felodipine (Plendil)

DHP; vascular-selective; grapefruit interaction (significant — 3x concentration increase).

Diltiazem (Cardizem)

Non-DHP; rate control in AFib/flutter; moderate negative inotrope; avoid in systolic HF.

Verapamil (Calan, Isoptin)

Non-DHP; greatest cardiac effect; most negative inotrope among CCBs; SVT treatment; avoid in HFrEF.

Class-Wide Side Effects

Common Side Effects

Peripheral edema (dose-dependent; especially DHPs — ankle edema due to selective arteriolar dilation)
Headache and flushing (vasodilation)
Dizziness
Reflex tachycardia (short-acting DHPs) — use long-acting formulations
Constipation — most common with verapamil

Serious Side Effects

Bradycardia and heart block — non-DHPs especially
Negative inotropy — may worsen systolic heart failure (non-DHPs)
Gingival hyperplasia — nifedipine especially
Medicine toxicity/overdose — high-dose CCBs cause profound hemodynamic collapse; treat with insulin-dextrose therapy and lipid emulsion

Class Medicine Interactions

Beta-blockers + non-DHP CCBs → additive bradycardia and heart block

CYP3A4 inhibitors (azoles, macrolides, grapefruit) → increase most CCB levels

Simvastatin + amlodipine → increased statin exposure (FDA warns max simvastatin 20mg with amlodipine)

Cyclosporine + diltiazem/verapamil → increased cyclosporine levels

Digoxin + verapamil/diltiazem → increased digoxin levels and bradycardia

Contraindications

!Non-DHP CCBs (diltiazem, verapamil): HF with reduced EF, severe bradycardia, sick sinus syndrome, 2nd/3rd degree AV block without pacemaker
!Cardiogenic shock
!Acute MI in hemodynamically unstable patient

Monitoring Parameters

Blood pressure and heart rate
Signs of edema (especially ankles)
Signs of bradycardia or AV block (non-DHPs)
Gingival health (nifedipine)
Constipation (verapamil)

Frequently Asked Questions

Why does amlodipine cause ankle swelling?

Amlodipine preferentially dilates arterioles over venules. This creates a hydrostatic pressure imbalance in capillaries — increased inflow pressure pushes fluid out into interstitial tissues, especially at the ankles due to gravity. This edema is not from fluid retention (unlike HF edema) and does not respond to diuretics. Dose reduction or switching agents resolves it.

Why can't I eat grapefruit with some calcium channel blockers?

Grapefruit contains furanocoumarins that irreversibly inhibit intestinal CYP3A4, the enzyme that metabolizes most CCBs. A single glass of grapefruit juice can increase felodipine levels by up to 3-fold and amlodipine/nifedipine levels significantly. This increases hypotensive effects and side effects. Avoid grapefruit with all CYP3A4-metabolized medications.