About calcium channel blockers (CCBs)
First identified in the late 1960s and introduced into more widespread usage in the 1980s, calcium channel blockers (CCBs or calcium antagonists) are non-habit-forming medications that are used to lower blood pressure and reduce the workload on the heart. Calcium is considered an excitatory element, meaning that its entry into certain kinds of cells causes them to contract.
Calcium channel blockers fall into two categories. One kind of calcium channel blockers affects the contractile strength of the heart tissue and the electrical conduction system. The other kind is a more potent vasodilator that causes arteries to relax and widen. The choice of calcium channel blockers depends on the underlying condition being treated. For example, heart rhythm problems (arrhythmias) may be treated with a calcium channel blocker that regulates the heart's conduction system, while high blood pressure might be treated with a vasodilator.
Arterial smooth muscle cells and cardiac muscle cells are sensitive to calcium. During a normal heartbeat, voltage sensitive channels open in the heart, allowing calcium ions to flow into cells, which causes them to contract. By blocking this flow of calcium ions, it is possible to reduce the contractile force of the heart and arteries. This relaxes them, reducing blood pressure and increasing the supply of oxygen-rich blood to the heart. Thus, calcium channel blockers are considered a kind of vasodilator.
Calcium channel blockers are generally taken in tablet or capsule form. The medication typically begins to affect body systems within one to two hours after each dose.
Although they were prescribed more heavily in the past, the worldwide use of calcium channel blockers, especially fast-acting CCBs, has been declining in recent years as other medications have proven more effective with fewer side effects. However, there are still situations in which a calcium channel blockers, especially a long-acting CCB, may be prescribed.
Calcium channel blockers are organized into two categories, depending on their chemical properties. The groups are:
- Dihydropyridines (this group includes common CCBs such as nifedipine, amlodipine, nicardipine, nitrendipine, and others). These drugs are powerful vasodilators.
- Non-dihydropyridines (this group includes verapamil and dilitiazem). These drugs affect the electrical conduction system and the heart's contractile strength.
Each of these categories operates by similar but slightly different mechanisms. The dihydropyridines, for example, are the most potent vasodilators and therefore have the strongest side effects. This group is further divided into fast-acting, intermediate and long-acting.
Verapamil, by contrast, is not as strong a vasodilator but may worsen heart failure, especially among patients who are also being treated with a beta blocker. Diltiazem falls somewhere between these two and is often the best tolerated CCB. The decision to prescribe any particular CCB over another depends on the unique case and the presence of side effects or other cardiac conditions.
In addition to standard CCB medications, a number of combination therapies may be used. For instance, medications may combine a calcium channel blocker with a diuretic in one pill. Recent studies, however, have shown that patients who are on combination calcium channel blocker and diuretic therapy have a higher risk of developing heart disease than patients who are on diuretics alone or a combination of diuretics and beta blockers.
Besides diuretics, calcium channel blockers may also be combined with low doses of several antihypertensive medications (e.g., ACE inhibitors, A-II blockers, beta blockers).
Calcium channel blockers (CCBs) are prescribed for a variety of conditions, including:
- High blood pressure (hypertension). Higher than normal blood pressure (the force of blood against the artery walls). While CCBs lower blood pressure on their own, they are sometimes combined with other antihypertensive medications (most commonly diuretics). CCBs are not usually considered the first-line treatment of high blood pressure.
- Angina. A type of chest pain, pressure or discomfort that is associated with coronary artery disease. Generally, CCBs are used only in patients with stable angina who have not responded to other forms of medication, including beta blockers or nitrates. Stable angina occurs during or after a known trigger, such as exercise or smoking. They are not prescribed for unstable angina, where pain occurs unpredictably.
- Coronary artery disease (CAD). In addition to relieving symptoms associated with CAD (e.g., angina pain), other uses for CCBs are being explored. For instance, patients who have balloon angioplasty or stenting to open clogged arteries run the risk of those arteries re-closing at a later time (a condition called restenosis). Research has suggested that CCB use can help reduce the risk of restenosis. A few studies have also suggested that certain CCBs may slow the progression of atherosclerosis, a disease in which the coronary arteries are gradually clogged with hardened plaque deposits.
- Coronary spasm. An abnormal tightening of the muscle fibers of the coronary artery. Calcium channel blockers are usually the first medication used in treating chest pain caused by a coronary spasm.
- Arrhythmia. An abnormal heartbeat resulting from any change or malfunction in the heart’s electrical system. Certain types of calcium channel blockers (e.g., verapamil, diliatzem) may be used to treat a form of arrhythmia called supraventricular tachycardia – a fast heart beat originating in the upper chambers of the heart (atria) or A-V node. Also, CCBs are used to treat a type of arrhythmia called atrial fibrillation. These drugs are not generally used to treat arrhythmias that originate in the lower chambers of the heart (ventricles).
- Past subendocardial infarction. A type of heart attack. CCBs may be prescribed to help reduce a person’s risk of having another subendocardial infarction. However, these drugs are not indicated after most types of heart attacks.
- Subarachnoid hemorrhage. A kind of ischemic stroke characterized by bleeding between the brain and the skull that is usually caused by a ruptured aneurysm. Calcium channel blockers may be used in both the prevention and treatment of this life-threatening condition.
- Hypertrophic cardiomyopathy. A disease in which the heart muscle is significantly thickened, characterized by abnormally strong contractions and impaired relaxation. CCBs can help people with this disease by reducing the heart’s workload. CCBs may also reduce the severity of obstructions to the left ventricular outflow tract, which is frequently observed in these patients.
- Raynaud syndrome. A disease that affects the small arteries in the extremities. People with Raynaud's suffer from episodes of ischemia (lack of blood flow) that causes the affected areas to turn blue and white. These episodes may be triggered by exposure to cold.
- Migraine or cluster headaches.
- Esophageal spasm.
- Preterm (premature) labor.
Conditions of concern
Patients should not take calcium channel blockers if they have been diagnosed with low blood pressure (hypotension). Calcium channel blockers may lower blood pressure to dangerous levels. In addition, patients should discuss with their physician the benefits and risks of taking calcium blockers if they have been diagnosed with any of the following conditions:
- Heart failure. The use of verapamil and diltiazem may slow cardiac conduction and reduce the contractile strength of the heart, potentially worsening heart failure. These drugs are generally contraindicated for patients with heart failure. This is not true for the long-acting dihydropyridines, which may be prescribed for patients with angina or high blood pressure in addition to heart failure.
- Heart attack (acute myocardial infarction). Large doses of fast-acting CCBs are linked to increased mortality and should therefore be avoided. However, certain calcium channel blockers may benefit some heart attack patients.
- Kidney or liver disease. These conditions may cause calcium channel blockers to be removed from the body at a slower rate, increasing the risk of overdose and/or side effects
- Abnormal heart rhythms (arrhythmias). Some types of calcium channel blockers may cause serious heart rhythm problems in patients with a history of arrhythmias (e.g., bradycardia, heart block).
- Clinical depression (or history of depression). Certain CCB (e.g., flunarizine) may cause depression in some patients.
- Parkinson’s disease (or similar disorders). A chronic progressive central nervous system disorder marked by tremors, a shuffling walk and weakness of resting muscles. Use of certain CCBs (e.g., flunarizine) may cause Parkinson-like symptoms in some patients.
- Other heart conditions. CCB use may worsen some other heart-related conditions.
Furthermore, preliminary studies suggested a link between calcium channel blocker use and an increased risk of breast cancer, particularly in postmenopausal women. Subsequent investigations found no substantial association between calcium channel blockers and breast cancer. Patients should discuss all the risks and benefits of this medication with their physicians.
- Side effects
Potential side effects of calcium channel blockers
Side effects will vary greatly depending on the type and dosage of calcium channel blocker (CCB) prescribed. The dihydropyridines, because of their potent vasodilator effect, are more likely to result in side effects such as:
- Dizziness or lightheadedness
- Swelling (edema)
The major side effect to verapamil, by contrast, is constipation, which occurs in more than 25 percent of patients.
Other conditions that should be immediately reported to a physician include:
- Allergic reaction. Symptoms may include shortness of breath, coughing, wheezing sneezing, respiratory congestion, itchiness and/or skin rash.
- Bradycardia. An abnormally slow heart rate that may cause fainting (syncope).
- Low blood pressure (hypotension). Abnormally low blood pressure, which may cause severe dizziness or lightheadedness.
- Heart block. Delayed or complete lack of communication between the upper and lower chambers of the heart.
- Tachycardia. An abnormally fast heart rate that may cause a pounding heartbeat (palpitations).
- Central nervous system imbalance (rare). This can manifest as loss of balance control, tremors, a shuffling walk, difficulty speaking or swallowing, a mask-like face, insomnia, nightmares, vivid dreams, depression or psychosis.
One of the more common side effects of calcium channel blockers is a brief headache that occurs shortly after taking the medication. This generally improves over time as the patient adjusts to the medication. Other potential side effects of calcium channel blockers include:
- Muscle, back or joint pain (rare, but more common in older patients)
- Abdominal cramps or upset stomach (nausea)
- Dry mouth
- Numbness or tingling of hands and feet
- Chest pain (rare)
- Tenderness, swelling or bleeding of the gums (rare)
Drug or other interactions
Patients should consult their physicians before taking any other medication (either prescription or over-the-counter) or nutritional supplements. Of particular note to individuals taking calcium channel blockers are:
- Other antihypertensives. These include diuretics, beta blockers and ACE inhibitors. In combination with calcium channel blockers, there is a small chance that these medications could produce a severe drop in blood pressure. Still, calcium channel blockers are commonly and routinely prescribed with other antihypertensives. Patients should discuss the risks and benefits of combination therapies with their physicians.
- Some antiarrhythmics. Medications used to treat abnormal heart rhythms (arrhythmias). Use of CCBs may intensify the effects of these medications.
- Inotropes. Medications that strengthen the heart’s contractions and are used in the treatment of heart conditions (e.g., tachycardia, heart failure).
- Corticosteroids. Cortisone-like anti-inflammatory medications used in the treatment of a number of conditions including asthma, skin irritation, nasal congestion and more.
- Some other medications including those used in the treatment of glaucoma, epilepsy or fungal infections.
- Over-the-counter (OTC) medications.
- Grapefruit juice.
- Recreational drugs, such as heroin, LSD and marijuana. Hypotension may occur with drugs used for erectile dysfunction, since these drugs are also vasodilators.
Calcium channel blockers are often prescribed in combination with nitrates when used to treat angina (a type of chest pain, pressure or discomfort).
When first taking calcium channel blockers (CCBs), patients should avoid operating heavy machinery (e.g., driving) until they know how the medication will affect them. Most patients on calcium channel blockers to treat high blood pressure (hypertension) will be taking the medication for the rest of their lives, provided no serious side effects occur. Patients should remember that calcium channel blockers control high blood pressure, but do not cure it. Even if all their symptoms are relieved, patients should continue to take their medication exactly as directed and to keep all scheduled follow-up appointments with their physicians.
Patients taking CCBs may be directed by their physicians to regularly monitor their heart rates. A heart rate lower than normal or below 50 beats per minute should be reported to a physician. Patients being treated for heart failure may need to weigh themselves frequently and report a loss or gain of more than five pounds in a week to their physician.
All patients are advised to carefully follow their physician’s instructions regarding exercise, activity level and diet. This is particularly important for patients taking this medication for the treatment of stable angina. When the frequency and intensity of chest pain caused by exercising is reduced due to the CCBs, patients may be tempted to overdo.
Patients should never stop taking this medication abruptly as it can cause serious side effects. This is especially true for patients with coronary artery disease because abrupt discontinuation may cause angina or heart attack. Since many people with CAD are not aware they have this condition, it is important that all patients who need to stop taking calcium channel blockers do so gradually and under the direction of a physician.
- How to use
Pregnancy use issues
Use during pregnancy must be evaluated on a case-by-case basis. These drugs will be prescribed if the physician decides that the benefits outweigh the risks. Although the effects of calcium channel blockers during pregnancy have not been studied in humans, animal studies have shown that large doses of certain calcium channel blockers can produce prolonged pregnancy, birth defects, poor bone development in the newborn and stillbirth. Other calcium channel blockers have shown no harm in animal studies.
When breast feeding, some calcium channel blockers will pass into breast milk, but this has not been found to cause problems in nursing infants.
Child use issues
There is no indication that the risk of side effects from calcium channel blockers is different in children than in adults. However, the safety of calcium channel blocker use in children has not been scientifically established. Parents are encouraged to discuss the potential risks and benefits with a pediatric cardiologist, before their children begin calcium channel blocker treatments.
Elderly use issues
Older adults report a higher frequency and intensity of side effects. Generally, older patients require lower doses of calcium channel blockers and are commonly prescribed these medications.
Symptoms of medication overdose
Overdose or accidental poisoning with calcium channel blockers (CCBs) is among the most lethal overdoses for prescription drugs. Because some of these medications are extended-release (or time-release) pills, symptoms of overdose can be delayed.
Patients exhibiting any of these signs or symptoms should contact their physician immediately:
- Severe bradycardia (low heart rate)
- Loss of consciousness or fainting (syncope)
- Swelling (edema)
- Weakness and easy fatigue
- Heart failure (in which the heart cannot pump enough blood to meet the body’s demand)
Questions for your doctorPatients may wish to ask their doctor the following questions related to calcium channel blockers:
- Which calcium channel blocker am I taking, and what is the dosage?
- What are the side effects of this medication?
- How long will it take after I take the drug before I would notice side effects?
- Which are "normal" side effects and which should cause concern?
- Is there any other medication I can take instead with fewer side effects?
- Are there any dietary supplements or nutrients that might affect this drug's function?
- How long will I be taking calcium channel blockers?
- Will this affect any of the other prescription medications I'm taking?
- Will this affect any OTC medications?
- Can I start, or continue, my exercise program?