Calcium Channel Blockers

Calcium Channel Blockers

     Calcium Channel Blockers (CCB) are used for the management of hypertension and angina. CCB protect cardiac tissue by inhibiting the entrance of calcium into cardiac and smooth muscle cells of the coronary and systemic arterial beds. All CCB are arteriolar vasodilators that decrease smooth muscle tone and vascular resistance. Compared to beta-blockers, CCB’s do not produce hyperlipidemia, insulin resistance, sedation, or sexual dysfunction.

The JNC 8 recommends a thiazide-type diuretic, CCB, ACE inhibitor, or ARB in nonblack patients with hypertension. In the general African American population, including those with diabetes, initial therapy should be a thiazide-type diuretic or CCB. There’re two general subclasses of calcium channel blockers: the dihydropyridines (DHP), which have greater selectivity for vascular smooth muscle cells, and the non-dihydropyridines which have greater selectivity for cardiac myocytes and are used for cardiac arrhythmias. The DHP’s can cause peripheral edema, dizzyness, and headaches. These potential adverse reactions are due to peripheral vasodilatory effects. The non-DHP’s are negative inotropes and chronotropes. This class can cause bradycardia and depress AV node conduction, increasing the risk of heart failure exacerbation, bradycardia, and AV block.



DHP and non-DHP



  • Have a direct effect on the myocardium, causing negative inotropy
  • Verapamil (Isoptin, Calan)
  • Diltiazem (Cardizem)



  • primary action on arterioles (DHP=Doesn’t Hurt Pulse)
  • Nifedipine (Aldat, Procardia)
  • Nimodipine
  • Amlodipine (Norvasc)
  • Felodipine
  • Isradipine



Effects CCBs


  • Arteries and arterioles dilate more than vein
  • Peripheral edema: more common with the DHP’s
  • Fall in BP due to reduced TPVR
  • Decreases HR and SV
  • Reflex tachycardia
  • Main side effect: Constipation- in both DHP’s and non-DHP’s (highest in Verapamil)
  • Headache, postural hypotension, and dizziness are relatively common with DHP’s
  • Avoid with severe HF or with other drugs that decrease contractility



  • Lesser effect on arterioles and depress AV node conduction
  • Can cause bradycardia and AV block, especially in patients with heart failure
  • HR should be monitored!


Indications CCBs

  • Hypertension
  • For acute reduction of blood pressure
  • In control of essential hypertension
  • Immediately after MI
  • In acute coronary artery syndrome
  • <36 hours prior to surgery
  • Vasospastic angina
  • Arrhythmias


Mechanism of Action (CCBs)

  • All block the inward movement of calcium through the slow channels of cell membranes of cardiac and smooth muscle cells
  • Non-DHP’s and DHP’s differ in their location of action. Non-DHP’s work on the cardiac conduction system. The DHP’s work on vascular smooth muscle.
  • CCB’s decrease automaticity in the SA node and decrease conduction in the AV node. This results in a negative chronotropic effect through the SA and AV node and prolongs AV refractory time.
  • Decreases force of smooth muscle contraction which results in coronary artery dilation
  • Lowers coronary resistance and improves blood flow through collateral vessels and oxygen delivery
  • Dilation of main coronary arteries/arterioles in both normal and ischemic areas
  • Reduces arterial pressure at rest and during exercise by dilating peripheral arterioles
  • Reduces afterload
  • Inhibits coronary artery spasm
  • Increases myocardial oxygen delivery
  • Responsible for effectiveness in vasospastic angina


Nifedipine (DHP) Adalat CC, Procardia XL

  • Potent dilator of vascular smooth muscle
  • Mild negative inotropic effect
  • Small increase in HR
  • No tendency to prolong AV conduction, prolong SA node recovery time, or slow sinus rate
  • More effective for HTN, but more likely to cause peripheral edema
  • No potential for arrhythmias


Verapamil (non-DHP)

  • Vascular smooth muscle dilator
  • Less potent than nifedipine
  • Significant negative inotropic effect
  • Slows conduction in the SA and AV nodes
  • Greater effect on AV node


Diltiazem (non-DHP)

  • Less negative inotropic effect than verapamil
  • Less peripheral vasodilation than nifedipine
  • Selectively has greater effect on cardiac muscle than on peripheral vascular smooth muscle
  • Slows conduction through the SA/AV nodes, but not as much as verapamil
  • Can cause a lupus-like rash



Treatment Principles CCBs

Verapamil and Diltiazem (non-DHP’s)

  • Significant effect on cardiac conduction
  • Antihypertension properties
  • Less likely to cause hypotension than nifedipine
  • More likely to cause conduction problems
  • Used to treat various arrhythmias, including atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia
  • Verapamil has more negative chronotropic effects than diltiazem
  • Co-administration of non-DHP’s with beta-blockers can cause significant AV nodal blockade which may produce heart block, bradycardia, cardiac conduction abnormalities and prolonged PR interval


Treatment of Stable Angina with CCBs

  • Effective in relieving symptoms and increasing exercise tolerance
  • Nitrates and betablockers remain first-line therapy
  • Reserved for patients with contraindications or adverse reactions to β-blockers or nitrates, and when symptoms are not well controlled with first-line agents
  • Long-acting diltiazem, verapamil, amlodipine, or felodipine should be used


How to Monitor CCBs

  • Weekly or biweekly while dosage is titrated
  • Once stable, monitor periodically every 3-6 months for adverse responses and control of disease process
  • Obtain and monitor serum digoxin levels if CCB are initiated in patients on digoxin
  • Renal and hepatic function periodically


Patient Variables CCBs


  • Use lower dosages
  • Generally well tolerated
  • Often the drug of choice in elderly patients.


  • Safety has not been established
  • Increasing experience with long-acting CCB’s in children with essential HTN has been safe and effective

Pregnancy and Lactation

  • Category C – Do not use
  • verapamil, diltiazem, and nifedipine are excreted in breast milk
  • Race and Gender
  • No gender differences have been noted
  • More effective in African Americans


Patient Education

  • Advise patients of potential hypotensive effects during dose titration
  • Report signs of CHF, irregular HR, nausea, constipation, dizziness, hypotension or edema
  • Nitrate therapy with CCB may cause dizziness
  • Do not take with grapefruit Juice
  • Many CCBs are cytochrome P450 3A4 substrates (verapamil has lots of drug interactions)


Phenylalkylamine (Verapamil)


  • Hypersensitivity, sick sinus syndrome or second- or third-degree heart block (except in patients with functioning pacemaker)
  • Hypotension <90 mm Hg
  • Patients with atrial flutter/fibrillation and an accessory AV pathway
  • May develop rapid ventricular response or V-fib


CCB Safety

  • DHPs, except Plendil and Norvasc may be detrimental in CHD.
  • Discontinue slowly tapering dose if used for angina
  • Diltiazem and verapamil is contraindicated in sick sinus syndrome, second & third degree heart block, severe CHF, and cardiogenic shock
  • Interacts with most statins and dramatically increases levels (except Pravachol and lescol)


Nondihydropyridines Dihydropyridines
-Avoid in CHF patients
-Acts on peripheral vasculature and heart
-Vasodilates smooth muscle
-↓Cardiac Depression= ↓HR ↓SV
-↓impulse conduction (may cause AV Block)
-Calcium channel antagonist block the movement of Ca+ by binding to L-type Calcium channels in heart/smooth muscle of heart/peripheral vasculature=smooth muscle relaxation and dilatation of arterioles
Therapeutic Uses
-Angina, SVT, migraine HA
-Less selective of any CCB
-Significant effects on both cardiac and vascular smooth muscle
Therapeutic Uses
-Asthma, DM, Angina, PVD, Migraines

-Works well with African Americans & elderly patients
Side Effects
-Avoid in severe HF (makes CHF worse)
Side Effects



Edmunds, M. W., & Mayhew, M. S. (2014). Pharmacology for the primary care provider (4th ed.). St. Louis, MO: Elsevier Mosby.

Harvey, R. A., Clark, M. A., Finkel, R., Rey, J. A., & Whalen, K. (2012). Pharmacology (5th ed.). Baltimore, MD: Lippincott.

JNC8 Guidlines 2014. (2014). JNC 8 Guidlines. Retreived from: