Calcium Channel Blockers

By Dr. Syeda Tahira Kazmi (pharm-D)

Cardiac effects

• Calcium-Channel Blockers decrease contractility (negative inotropy)
• Calcium-Channel Blockers decrease heart rate (negative chronotropy)
• Calcium-Channel Blockers decrease conduction velocity (negative dromotropy)

Vascular effects

• Smooth muscle relaxation (vasodilation)

Calcium channel blockers are prescription medications that relax blood vessels and increase the supply of blood and oxygen to the heart while also reducing the heart’s workload. Examples of calcium channel blockers include:

• Amlodipine (Norvasc) Bepridil (Vascor)
• Diltiazem (Cardizem, Cardizem CD, Cardizem SR, Dilacor XR, Diltia XT, Tiazac)
• Felodipine (Plendil)
• Nicardipine (Cardene, Cardene SR)
• Nifedipine (Adalat, Adalat CC, Procardia, Procardia XL)
• Nisoldipine, (Sular)
• Verapamil (Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM)

Caduet is a combination of a statin cholesterol drug and amlodipine.

Different Classes of Calcium-Channel Blockers

There are three chemical classes of CCBs. They differ not only in their basic chemical structure, but also in their relative selectivity toward cardiac versus vascular L-type calcium channels. The most smooth muscle selective class of CCBs are the dihydropyridines. Because of their high vascular selectivity, these drugs are primarily used to reduce systemic vascular resistance and arterial pressure, and therefore are used to treat hypertension. Extended release formulations or long-acting compounds are used to treat angina and are particularly affecting for vasospastic angina; however, their powerful systemic vasodilator and pressure lowering effects can lead to reflex cardiac stimulation (tachycardia and increased inotropy), which can offset the beneficial effects of afterload reduction on myocardial oxygen demand. Note that dihydropyridines are easy to recognize because the drug name ends in “pine.”

Dihydropyridines

include the following specific drugs:  (Go to www.rxlist.com for specific drug information)

• Amlodipine
• Felodipine
• Isradipine
• Nicardipine
• Nifedipine
• Nimodipine
• Nitrendipine

Non-dihydropyridines, of which there are only two currently used clinically, comprise the other two classes of CCBs. Verapamil (phenylalkylamine class), is relatively selective for the myocardium, and is less effective as a systemic vasodilator drug. This drug has a very important role in treating angina (by reducing myocardial oxygen demand and reversing coronary vasospasm) and arrhythmias. Diltiazem (benzothiazepine class) is intermediate between verapamil and dihydropyridines in its selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, diltiazem is able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines

General Pharmacology

Currently approved calcium-channel blockers (CCBs) bind to L-type calcium channels located on the vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into muscle cells, which in turn stimulates smooth muscle contraction and cardiac myocyte contraction. In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents and in phase 0 of the action potentials. Therefore, by blocking calcium entry into the cell, CCBs cause vascular smooth muscle relaxation (vasodilation), decreased myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decreased conduction velocity within the heart (negative dromotropy), particularly at the atrioventricular node.

Indications 

• Heart conditions that calcium channel blockers might be prescribed for:
• High blood pressure (especially in African Americans)
• Coronary artery disease
• Coronary spasm
• Angina (chest pain)
• Abnormal heart rhythms
• Hypertrophic cardiomyopathy
• Diastolic heart failure (preserved left ventricular function)
• Raynaud’s syndrome (a circulatory problem affecting blood vessels in the hands and feet)
• Pulmonary hypertension (high blood pressure in the arteries of your lungs)
• If you have systolic heart failure, then amlodipine and felodipine are the only calcium channel blockers you should use.
• Calcium channel blockers can also prevent migraine.

Directions:

Calcium channel blockers should be taken with food or milk. Follow the label directions on how often to take it. The number of doses you take each day, the time allowed between doses, and how long you need to take it will depend on the type of medication your doctor prescribed and why.

Other Guidelines for Taking Calcium Channel Blockers

While taking calcium channel blockers, have your blood pressure checked regularly, as advised by your doctor.

Keep all appointments with your doctor and the laboratory so that your response to the drug can be monitored.

While taking this medication, your doctor may tell you to take and record your pulse daily. Your provider will tell you how rapid your pulse should be. If your pulse is slower than advised, contact your doctor about taking your calcium channel blocker that day.

You should check your blood pressure regularly. Ask your doctor how often.

You may need to take and record your pulse daily. If it’s slower than your doctor said it should be, call your doctor or nurse to find out if you should still take your calcium channel blocker that day.

Side Effects

Side effects of calcium channel blockers can include:

• Lightheadedness
• Low blood pressure
• Slower heart rate
• Drowsiness
• Constipation
• Swelling of feet ankles and legs
• Increased appetite.
• Gastroesophageal reflux disease (GERD)
• Tenderness or bleeding of the gums
• Sexual dysfunction

Let your doctor know if these side effects are severe or don’t go away. Contact your doctor right away if you:

• Gain weight
• Have trouble breathing (shortness of breath, coughing, or wheezing)
• Get a skin rash or hives
• Are very lightheaded or faint.

Food and Drug Interactions

Do not eat grapefruit or drink grapefruit juice while you’re taking a calcium channel blocker.

Avoid alcohol because it can change how calcium channel blockers work and make the side effects worse.

Your doctor needs to know about all the medications you’re taking, to avoid problems with calcium channel blockers. Talk to your doctor before you take anything new, including over-the-counter drugs, herbs, and supplements.

patients having preexistent bradycardia, conduction defects, or heart failure caused by systolic dysfunction should not be given CCBs, especially the cardiac selective, non-dihydropyridines. CCBs, especially non-dihydropyridines, should not be administered to patients being treated with a beta-blocker because beta-blockers also depress cardiac electrical and mechanical activity and therefore the addition of a CCB augments the effects of beta-blockade.

Are They Safe for Pregnant Women, Kids, and Older People?

Calcium channel blockers can be used during pregnancy to manage high blood pressure and preeclampsia. However, you should always consult with your doctor before taking calcium channel blockers during pregnancy.

These drugs may pass into breast milk, but no adverse effect on breastfed infants has been found. Discuss the risks and benefits of using calcium channel blockers while breastfeeding with your doctor.

The safety of calcium channel blockers in children has not been established; however, no problems have been found to date. Discuss the risks and benefits of giving your child calcium channel blockers with your child’s doctor.

Older adults have more side effects from calcium channel blockers than younger people. Doctors usually prescribe lower doses.

Heart Failure and Calcium Channel Blockers

Calcium channel blockers may be used to treat heart failure caused by high blood pressure when other medications to lower blood pressure do not work. Calcium channel blockers generally should not be used if you have heart failure due to systolic dysfunction.