Calcium Channel Blockers (CCBs)

Calcium channel blockers are drugs that block the entry of calcium into the muscle cells of the heart and arteries.

• The entry of calcium is critical for the conduction of the electrical signal that passes from muscle cell to muscle cell of the heart, and signals the cells to contract.
• It also is necessary in order for the muscle cells to contract and thereby pump blood.
• In the arteries, the entry of calcium into muscle cells constricts the arteries.

Thus, by blocking the entry of calcium, calcium channel blockers reduce electrical conduction within the heart, decrease the force of contraction (work) of the muscle cells, and dilate arteries.

• Dilation of the arteries reduces blood pressure and thereby the effort the heart must exert to pump blood.
• Combined with decreases in the force of contraction, this leads to a reduced requirement for oxygen by the heart.
• Dilation of the arteries provides more oxygen-carrying blood to the heart.
• The combination of reduced demand for oxygen and increased delivery of oxygen prevents angina or heart pain. (Angina occurs when the heart is not getting enough oxygen relative to the amount of work it is doing.)
• In addition, calcium channel blockers slow electrical conduction through the heart and thereby correct abnormal rapid heartbeats.

Calcium channel blockers are approved for treating:

• high blood pressure,
• angina,
• abnormal heart rhythms (for example, atrial fibrillation, paroxysmal supraventricular tachycardia) and subarachnoid hemorrhage.

They are also used for treating other conditions such as:

• high blood pressure in the pulmonary arteries (pulmonary hypertension),
• Raynaud's phenomenon, cardiomyopathy (disease of the heart's muscle), and
• preventing migraine headaches.

Although calcium channel blockers have a similar mechanism of action, they differ in their ability to affect heart muscle vs. arteries, and they differ in their ability to affect heart rate and contraction. These differences determine how they are used and their side effects.

For example:

• verapamil (Covera-HS, Verelan PM, Calan), and diltiazem (Cardizem LA, Tiazac) reduce the strength and rate of the heart's contraction and are used in treating abnormal heart rhythms; and
• amlodipine (Norvasc) has very little effect on the heart rate and contraction. Therefore, amlodipine is not used for treating abnormal heart rhythm, but it is preferred when heart failure is present and dilation of arteries is desired.

Common side effects of calcium channel blockers include:

• headache,
• constipation,
• rash,
• nausea,
• flushing,
• edema (fluid accumulation in tissues),
• drowsiness,
• low blood pressure, and
• dizziness.

Sexual dysfunction, overgrowth of gums, and liver dysfunction also have been associated with calcium channel blockers. Verapamil (Covera-HS, Verelan PM, Calan) and diltiazem (Cardizem LA, Tiazac) worsen heart failure because they reduce the ability of the heart to contract and pump blood.

Calcium channel blockers interact with several drugs.

• Verapamil (Covera-HS, Verelan PM, Calan) and diltiazem (Cardizem LA, Tiazac) reduce the elimination and increase the blood levels of carbamazepine (Tegretol), simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor). This can lead to toxicity from these drugs.
• Several calcium channel blockers [for example, diltiazem (Cardizem LA, Tiazac), felodipine (Plendil)] increase the level of cyclosporine (Sandimmune, Neoral, Restasis) and similarly lead to toxicity of cyclosporine.
• Grapefruit juice (1 glass, approximately 200ml) may elevate serum concentrations of verapamil (Covera-HS, Verelan PM, Calan), felodipine (Plendil), nifedipine (Adalat, Procardia), nicardipine (Cardene), nisoldipine (Sular), and possibly amlodipine (Norvasc).

The calcium channel blockers available in the U. S. are:

• amlodipine (Norvasc),
• diltiazem (Cardizem LA, Tiazac),
• felodipine (Plendil),
• isradipine (Dynacirc),
• nifedipine (Adalat, Procardia),
• nicardipine (Cardene),
• nimodipine (Nimotop),
• nisoldipine (Sular), and
• verapamil (Covera-HS, Verelan PM, Calan).

Verapamil, diltiazem and nicardipine (Cardene IV) also are available in intravenous formulations.