Calcium channel blockers comprise three chemical groups, all of them bind the L-type Ca++ channel, but

each class binds to different binding sites of the same channel:

Phenilalkylamines: verapamil is the only drug in this group, it binds to the V binding site. Benzothiazepines: diltiazem binds to the D binding site in the L-type Ca++ channel. It shows cardiovascular effects similar to those of verapamil. Dihydropyridines: the prototype agent in this group is nifedipine, a first generation dihydropyridine that binds to the N binding site. Second generation agents include isradipine, nicardipine, and felodipine. Amlodipine is considered a third generation dihydropyridine.

Calcium channel antagonists block the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature. CCBs dilate coronary arteries and peripheral arterioles, but not veins. They also decrease cardiac contractility (negative inotropic effect) ,automaticity at the SA node and conduction at the AV node. Dilation of the coronary arteries increases myocardial oxygen supply.

Dihydropiridines have minimal effect on cardiac conduction or heart rate, while they have potent actions as arteriolar vasodilators. This class of drugs can cause reflex tachycardia when peripheral vasodilation is marked. On the other hand, verapamil and diltiazem slow AV conduction and decrease SA node automaticity, they also decrease heart rate. Diltiazem is used in the

treatment of variant angina because of its coronary antispasmodic properties. Indications

Dihydropiridines indications Hypertension CCBs effectiveness in the treatment of hypertension is related to a decrease in peripheral resistance accompanied by increases in cardiac index. CCB are also useful in the treatment of hypertensive patients with comorbidities such as: asthma, diabetes, angina, ond or peripheral vascular disease. Angina pectoris Calcium channel blockers act as coronary vasodilators, producing variable and dosedependent reductions in myocardial oxygen demand, contractility, and arterial pressure. These combined pharmacologic effects are advantageous and make these agents as effective as beta blockers in the treatment of angina pectoris. They are indicated when beta blockers are contraindicated, poorly tolerated, or ineffective. In the presence of heart failure, the use of calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Supraventricular tachyarrhythmias

Verapamil and diltiazem are class IV antiarrhythmics, according to Vaughan and Williams classification of antiarrhythmic drugs. This is based on their depressant action at the SA and AV nodes. Their ability to inhibit the AV node is employed in the management of supraventricular tachyarrhythmias, such as: atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia.