**6.3 Nicardipine**

It is a short-acting dihydropyridine with a side effect profile similar to nifedipine; it has also been shown to be useful in angina. It is remarkably effective in vasospastic angina.

#### **6.4 Felodipine**

It is a second-generation dihydropyridine channel blocker of the nifedipine type. It is more selective for vascular smooth muscles than myocardial tissue. And it serves as an effective vasodilator. It is usually used in the treatment of angina and essential hypertension. Additionally, it exhibits a high degree of protein binding and has a half-life ranging from 10 to 18 hours.

#### **6.5 Nimodipine**

It is a dihydropyridine calcium channel blocker that differs from other dihydropyridines as it dilates the cerebral blood vessels more than other dihydropyridines do. It is indicated in the treatment of subarachnoid hemorrhage-associated neurological deficits.

#### **6.6 Verapamil**

It is a phenylalkylamine. It was introduced in 1962 as a coronary vasodilator. It is used for the treatment of angina pectoris, arrhythmias due to ischemic cardiac syndromes, and supraventricular arrhythmias as well. Verapamil's primary effect is on the slow Ca2+ channel, which results in a slowing of AV conduction and the sinus rate. It has a rapid absorption following oral administration. However, it is metabolized quickly and, therefore, has low bioavailability. Its main site of firstpass metabolism is the liver, forming several products. Yet, its metabolites have no significant biological effects. Verapamil has an elimination half-life of around 5 hours. Verapamil, like the dihydropyridines, causes little impact on venous return and preload but has more direct negative inotropic and chronotropic effects than the dihydropyridines at doses that produce arteriolar dilation and afterload reduction (**Figure 4**). Thus, the consequences of a reflex increase in adrenergic tone are generally offset by the direct cardio depressant effects of the drug. In patients without heart failure, oral administration of verapamil reduces peripheral vascular resistance and blood pressure with minimal changes in heart rate. Ventricular performance is not impaired and may improve, especially if ischemia limits performance. In contrast, in patients with heart failure, intravenous verapamil can cause a marked decrease in contractility and left ventricular function. The antianginal effect of verapamil, like that of all Ca2+ channel blockers, is due primarily to a reduction in myocardial O2 demand [7].

#### **6.7 Diltiazem**

It was introduced in Japan as a cardiovascular agent for the treatment of angina pectoris. It was detected to dilate peripheral arteries and arterioles. By relieving coronary artery spasm, diltiazem increases myocardial oxygen supply, and by decreasing heart rate, it reduces myocardial oxygen demand. It is used in patients with variant angina as well. Additionally, it has electrophysiological properties similar to those of verapamil and, therefore, is used as an antiarrhythmic agent, but it is less potent than verapamil. It has a rapid oral absorption through the digestive tract, and it reaches peak plasma

**225**

*Calcium Channel Blockers*

potency of the parent drug [7].

often occurs with continued use.

rapid-release formulations.

• Gum hyperplasia.

to lower esophageal sphincter relaxation.

**7. Calcium channel blocker indications**

**7.1 Calcium channel blockers for hypertension**

tion against stroke than other antihypertensive agents do.

**7.2 Calcium channel blockers for coronary vasospasm**

**6.8 Side effects**

diuretics.

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

levels within 1 hour of administration. Nevertheless, the sustained-release prepara-

Diltiazem is metabolized extensively by the first-pass metabolism after oral administration. Hence, its bioavailability is about 40%. It undergoes several biotransformations, including deacetylation, oxidative O- and N-demethylations, and conjugation of the phenolic metabolites. Although it has various metabolites, only deacetyldiltiazem is pharmacologically active, which has about 40–50% of the

• Headache, flushing, and dizziness due to arterial dilation, although tolerance

• Ankle edema probably arises from increased transcapillary hydrostatic pressure. It happens mostly with dihydropyridines, and it is frequently resistant to

• Decompensated heart failure is due to reduced cardiac contractility, especially in patients with preexisting poor left ventricular function, particularly with

• Tachycardia and palpitations can arise with dihydropyridines, especially with

• Heartburn associated with Amlodipine and other dihydropyridines use is due

CCBs are prevalent antihypertensive drugs. CCBs lower BP by causing peripheral arterial dilation, with the rank order of potency being dihydropyridines > diltiazem > verapamil. They are generally well-tolerated, do not require monitoring with blood tests, and have proven safe and effective in many large RCTs. CCBs also have antianginal and some antiarrhythmic effects and seem to provide more protec-

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and subsequent RCTs showed that CCBs (represented by amlodip-

Coronary spasm results in transient functional occlusion of a coronary artery that is reversible with nitrate vasodilation. It occurs in the setting of coronary

ine) prevent coronary events as effectively as diuretics and RAS blockers do.

verapamil, but amlodipine does not depress cardiac contractility.

• Bradycardia and heart block can occur with verapamil and diltiazem.

• Constipation is most common with verapamil and less with diltiazem.

tions provide peak plasma levels within 3–4 hours of oral administration.
