Calcium channel antagonists are currently given to treat hypertension after having first been used as antianginal and antiarrhythmic agents. An increase in intracellular calcium in vascular cells plays a major role in the pathogenesis of high blood pressure. By preventing the influx of calcium into cells, calcium channel blockers induce vasodilatation of arterioles and increase the diameter of large vessels, thereby reducing blood pressure and reversing left ventricular hypertrophy. In addition, calcium entry blockers preserve regional blood flow (in coronary, cerebral and renal beds), have a natriuretic effect and do not induce water and sodium retention. Effects on heart rate and myocardial contractility vary across molecules. When used as single drug therapy, calcium channel blockers lower blood pressure as effectively as the other major antihypertensive agents (at least 50 % of cases of mild to moderate hypertension are controlled), but this activity concerns a broader spectrum of patients since it is not influenced by age, race or renin status. Long-term studies are still needed to determine whether reversal of left ventricular hypertrophy will reduce morbidity (coronary and cerebrovascular risk) and mortality in hypertensive patients. Calcium channel antagonists can be given concomitantly with diuretics but synergy is observed mainly with beta-blocking agents and conversion enzyme inhibitors. In some forms of high blood pressure, including exacerbations of hypertension and preparation to surgery for pheochromocytoma, calcium channel blockers have proved especially useful and effective. No severe side effects have been reported. Calcium channel antagonists are not responsible for metabolic disorders (lipids, serum glucose) or arrhythmogenic electrolyte disorders that may offset the beneficial effect of lower blood pressure. However, mild but troublesome side effects (headache, dizziness, flushing, nausea, constipation, edema of the lower limbs) are common (20 to 30 % of patients), although they require discontinuation of the treatment in only 4 to 13 % of cases. These adverse effects are marked at the beginning of treatment and may abate subsequently; they are less common with sustained-release once-daily forms. Calcium channel blockers are well tolerated even in high risk hypertensive patients with comorbid conditions such as coronary heart disease, arterial occlusive disease, asthma, or renal failure. The quality of life of the treated hypertensive patient can thus be preserved. In sum, calcium channel antagonists nearly fit the definition of the ideal antihypertensive agent and deserve to be considered as step 2 in the stepped-care approach, along with the other major antihypertensive agents and second only to lifestyle changes.
