Pharmacology of Calcium Channel Blockers

Calcium Channel Blockers
Calcium channel blockers are considered third-choice agents in the treatment of stable angina, certain dysrhythmias, and hypertension.

Mechanism of Action
Calcium channel blockers are a type of drug that block the entry of calcium into smooth muscle cells as well as myocytes. They produce arterial vasodilation and thereby reduce arterial blood pressure. They also reduce myocardial contractility, resulting in reduction of myocardial oxygen consumption.

Indications
Calcium channel blockers are used to treat exertional angina that is not controlled by nitrates, and in combination with beta-blockers. This combination provides the most effective therapy. They are considered the drug of choice in the treatment of angina at rest. Diltiazem and verapamil will reduce the heart rate. Nifedipine, amlodipine, and felodipine are among the most potent calcium-blocking agents. β-blockers are recommended as the first-line treatment of angina pectoris, but if they are not tolerated, calcium channel blockers can be administered. Diltiazem and verapamil can be used, but they have the disadvantage of depressing contractility more than dihydropyridines do. The therapeutic goal in medication use is to reduce the
frequency and intensity of anginal attacks without suppressing the cardiac action too much.

Adverse Effects
Common adverse effects related to the use of calcium channel blockers include: fl ushing, headaches, dizziness, hypotension, ankle edema, constipation, and palpitations. Combinations of nitrates, β-blockers, and calcium channel blockers are oft en preferred for treatment of angina pectoris, because these agents have fewer adverse eff ects.

Contraindications and Precautions
Calcium channel blockers are contraindicated in patients with a history of hypersensitivity to these drugs, hypotension, or cardiogenic shock. The major contraindications to combination therapy are associated with the use of β-blockers and calcium channel blockers, which may cause excessive
cardiac depression. Calcium channel blockers should be used with caution during pregnancy (category C) and lactation, and in patients with congestive heart failure, hepatic or renal dysfunction, and hypotension.

Drug Interactions
Calcium channel blockers increase risk of orthostatic hypotension with prazosin. Increased blood pressure may occur with aspirin, bismuth subsalicylate, or magnesium salicylate. Some calcium channel blockers increase serum levels and toxicity of cyclosporine.