Therapeutic Applications

THERAPEUTIC APPLICATIONS

The calcium channel–blocking drugs have been investi-gated for an unusually wide number of clinical applica-tions. Verapamil-induced improvement of diastolic func-tion has proved to be beneficial in the treatment of hypertrophic cardiomyopathy. Vasodilatory properties of these drugs are used in the treatment of peripheral vaso-constrictive disorders (Raynaud’s disease) and in reliev-ing vasospasm following subarachnoid hemorrhage. There is ongoing interest in investigating protective ef-fects on renal function and in the ability to reduce dele-terious vascular changes in diabetes mellitus. Similarly, the potential benefit afforded by their selective vasodila-tory action (especially the second-generation agents) in the management of heart failure is an area of interest. These drugs are of some benefit in a variety of noncar-diovascular conditions characterized by hyperactivity of smooth muscle (e.g., achalasia). However, their main ap-plications are as follows.

Hypertension

The calcium channel–blocking drugs are effective anti-hypertensive agents and enjoy widespread use as single medication or in combination. Their effectiveness is re-lated to a decrease in peripheral resistance accompanied by increases in cardiac index. The magnitude of their ef-fects is determined partly by pretreatment blood pres-sure levels; maximum blood pressure lowering gener-ally is seen 3 to 4 weeks after the start of treatment. These drugs possess some distinct advantages relative to other vasodilators, including the following:

·              Their relaxant effect on large arteries results in greater compliance, which is beneficial in older persons.

·              Tolerance associated with renal retention of fluid does not occur; an initial natriuretic effect is often observed, especially with the nifedipine group of blockers.

·              They do not have significant effects on the re-lease of renin or cause long-term changes in lipid or glucose metabolism.

·              Postural hypotension, first-dose effect, and re-bound phenomenon are not commonly seen.

Their antihypertensive efficacy is comparable to that of β-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors. The choice of a calcium chan-nel blocker, especially for combination therapy, is largely influenced by the effect of the drug on cardiac pacemakers and contractility and coexisting diseases, such as angina, asthma, and peripheral vascular disease.

Ischemic Heart Disease

The effectiveness and use of calcium channel blockers in the management of angina are well established ; their benefit in postinfarction stages is less certain. Efficacy in angina is largely derived from their hemodynamic effects, which influence the supply and demand components of the ischemic balance (1) by in-creasing blood flow directly or by increasing collateral blood flow and (2) by decreasing afterload and reducing oxygen demand. All three agents are useful in the man-agement of stable exertional angina, with their vasodila-tory and cardiac effects making beneficial contributions. Given the differences in their relative effects (Table 19.1), the response of the patient can vary with the agent used and the preexisting cardiac status.

All agents are also effective in the control of variant (Prinzmetal’s) angina, in which spasm of the coronary arteries is the main factor. Their usefulness in the more complex unstable (preinfarction) angina is less definite, depending on the hemodynamic status and the suscep-tibility of the patient to infarction.

Cardiac Arrhythmias

The prominent depressant action of verapamil and dil-tiazem at the SA and A-V nodes finds use in specific ar-rhythmias. They are of proven efficacy in acute control and long-term management of paroxysmal supraventric-ular tachycardia .Their ability to inhibit conduction at the A-V node is employed in protecting ventricles from atrial tachyarrhythmias, often in combi-nation with digitalis or propranolol.