**5. Cardiovascular effects of different Ca2+ channel blockers**

The hemodynamic profiles of the Ca2+ channel blockers approved for clinical use differ and depend mainly on the ratio of vasodilating and negative inotropic and chronotropic effects on the heart (**Table 1**, **Figures 4** and **5**). Although all calcium channel blockers are vasodilators, dihydropyridine derivatives such as nifedipine and amlodipine are the most potent and have the most significant vascular selectivity. Arterial dilation reduces peripheral resistance and lowers blood pressure, which reduces the work of the left ventricle and therefore reduces myocardial oxygen demand. Most dihydropyridines have a rapid onset of action. A rapid reduction in blood pressure can lead to reflex sympathetic nervous system activation and tachycardia. Amlodipine or modified-release formulations of short-acting dihydropyridines are more slowly absorbed and gradually reduce blood pressure with little reflex tachycardia. But generally, the differences between the relatively vaso-selective dihydropyridines and the much less-selective diltiazem and verapamil have essential consequences because the decrease in arterial blood pressure elicits reflex sympathetic activation, resulting in the stimulation of heart rate, AV conduction velocity, and myocardial force, just the opposite of the direct effect of Ca2+ channel blockers. While direct and indirect impacts usually balance each other in the case of verapamil and diltiazem, sympathetic stimulation often prevails in dihydropyridines, causing an increase in heart rate and contractility. Cardiac depressant effects


#### **Table 1.**

*Comparative cardiovascular effects of calcium channel blockers graded from 0 (no effect) to 5 (prominent effect).*

#### **Figure 4.**

*Effects of calcium channel blocker agents.*

#### **Figure 5.**

*Calcium channel blocker sites of action.*

of dihydropyridines may be unmasked, though, in the presence of β blockers and patients with heart failure.

Also, they can have a significant impact on coronary artery dilation; for this reason, CCB can prevent or relieve coronary vasospasm and improve myocardial blood flow. On the other hand, CCBs have negative chronotropic effect. Verapamil and diltiazem (but not the dihydropyridines) slow the rate of firing of the sinoatrial node and slow the conduction of the electrical impulse through the atrioventricular node. Reflex tachycardia does not occur with these drugs, and they also slow the rate of rising in heart rate during exercise. CCBs play an essential role in reducing cardiac contractility as most calcium channel blockers (particularly verapamil) have some negative inotropic effects. Amlodipine does not impair myocardial contractility.

**223**

*Calcium Channel Blockers*

**Figure 4**).

**6.1 Nifedipine**

**6.2 Amlodipine**

*DOI: http://dx.doi.org/10.5772/intechopen.90778*

**6. Calcium channel blocker agents**

**A.** Dihydropyridines: amlodipine, clevidipine, felodipine, isradipine, lercanidi-

Dihydropyridines exhibit much higher arterial vasodilation than nondihydropyridines while having relatively little impact on cardiac tissue (i.e., there is less depression on myocardial contractility, less impairment on SA node automaticity, and less slowing on AV node conduction velocity) (**Table 1**,

Non-dihydropyridines are more effective in tissue with frequent channel openings (i.e., SA node, AV node, and cardiac myocytes), and channel inhibition increases in proportion to heart rate. The negative chronotropic and inotropic effects on non-dihydropyridine agents appear greater for verapamil than diltiazem. The phenylalkylamine verapamil and the benzothiazepine diltiazem have both cardiac and vascular actions (**Table 1**, **Figure 4**). These drugs have antiarrhythmic,

It is a dihydropyridine that does not resemble the other calcium antagonists in chemical structure. Although it is not a nitrate, its nitro group is essential for its antianginal effect. Also, it has peripheral vasodilatory effects. It works by inhibiting the voltage-dependent calcium channel in the vascular smooth muscles and has little or no direct suppressant effect on the SA or AV nodes. Nifedipine is thought to be more effective in patients with coronary vasospasm, and it is usually used for

Additionally, it is used in selected patients to treat hypertension because of its vasodilatory properties. Nifedipine has efficient absorption with buccal or oral administration. Around 90% of nifedipine is protein-bound. The bioavailability of an oral dose reaches 65%. Nifedipine gets metabolized into two inactive metabolites which are found in equilibrium with each other. Only a limited amount of

Similar to second-generation dihydropyridines, it has a higher selectivity for the vascular smooth muscles than the myocardial tissue. It has a longer half-life (34 hours) but less negative inotropic effect than nifedipine. It is used in the treatment of chronic stable angina and essential hypertension [7]. Amlodipine increases exercise duration, decreases anginal attacks, and reduces the consumption of **nitroglycerin.** It is given once daily (at a dose of 5 or 10 mg). Common side effects

pine, nicardipine, nifedipine, nimodipine, and nisoldipine

There are two types of CCBs:

**B.** Non-dihydropyridines:

• Benzothiazepines (diltiazem)

• Phenylalkylamines (verapamil)

antianginal, and antihypertensive activity.

vasospastic angina along with angina pectoris.

unchanged nifedipine is found in the urine [7].

of the dihydropyridines are less likely with amlodipine**.**
