Calcium-Channel Blockers
Currently approved 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.
Therapeutic Use of
Hypertension
By causing vascular smooth muscle relaxation, CCBs decrease systemic vascular resistance, which lowers arterial blood pressure. These drugs primarily affect arterial resistance vessels, with only minimal effects on venous capacitance vessels.
Dihydropyridines include the following specific drugs:
Cardiac effects
- Decrease contractility
(negative inotropy) - Decrease heart rate
(negative chronotropy) - Decrease conduction velocity
(negative dromotropy)
Vascular effects
- Smooth muscle relaxation
(vasodilation)
Therapeutic Indications
CCBs are used to treat hypertension, angina and arrhythmias.Therapeutic Use of
Calcium-Channel Blockers
- Hypertension
(systemic & pulmonary) - Angina
- Arrhythmias
Angina
The anti-anginal effects of CCBs are derived from their vasodilator and cardiodepressant actions. Systemic vasodilation reduces arterial pressure, which reduces ventricular afterload (wall stress) thereby decreasing oxygen demand. The more cardioselective CCBs (verapamil and diltiazem) decrease heart rate and contractility, which leads to a reduction in myocardial oxygen demand, which makes them excellent antianginal drugs. CCBs can also dilate coronary arteries and prevent or reverse coronary vasospasm (as occurs in Printzmetal's variant angina), thereby increasing oxygen supply to the myocardium.Arrhythmias
The antiarrhythmic properties (Class IV antiarrhythmics) of CCBs are related to their ability to decrease the firing rate of aberrant pacemaker sites within the heart, but more importantly are related to their ability to decrease conduction velocity and prolong repolarization, especially at the atrioventricular node. This latter action at the atrioventricular node helps to block reentry mechanisms, which can cause supraventricular tachycardia.Different Classes of Calcium-Channel Blockers
There are three 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 primarily used to treat hypertension. They are not, however, generally used to treat angina because their powerful systemic vasodilator and pressure lowering effects can lead to reflex cardiac stimulation (tachycardia and increased inotropy), which can dramatically increase myocardial oxygen demand. Note that dihydropyridines are easy to recognize because the drug name ends in "pine." Dihydropyridines include the following specific drugs:
- amlodipine
- felodipine
- isradipine
- nicardipine
- nifedipine
- nimodipine
- nitrendipine
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