EFFICACY AND SAFETY OF FELODIPINE, A NEW DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKER, IN ELDERLY HYPERTENSIVE PATIENTS

Felodipine is a new dihydropyridine calcium channel blocker with a number of properties that enhance its suitability as a first-line antihypertensive drug for the elderly. Felodipine has a 100-fold selectivity for inhibiting the contribution of vascular smooth muscle compared with cardiac muscle. Negative inotropic action appears minimal while selectivity appears to increase with age. Felodipine has a minimal effect on smooth muscle of venous capacitance vessels, thereby greatly reducing the likelihood of orthostatic hypotension. Renal effects are favorable; the glomerular filtration rate is increased in some patients. The extended-release formulation of felodipine produces a smooth 24-hour plasma concentration curve and is effective when prescribed once daily. Felodipine appears to lower blood pressure effectively in the elderly patient with few, generally mild, adverse effects. Persisting misconceptions about the pathophysiology of hypertension and the possibility of exposing elderly patients to potentially serious side effects associated with diuretics and beta blockers have contributed to the reluctance of many clinicians to treat elderly patients with hypertension. In the National Health and Nutrition Examination Survey of 1985, it was estimated that fewer than 15% of elderly hypertensive patients were receiving adequate treatment (1). Diuretics and beta blockers have been among the more widely used antihypertensive drugs in both young and elderly patients. Although these agents are generally effective in lowering blood pressure, either as monotherapy or concomitantly with other drugs, adverse reactions tend to exert a negative impact on quality of life, particularly in the elderly. Side effects can be worrisome in elderly patients; for example, diuretic-induced hypokalemia can predispose the patient to potentially fatal arrhythmias during long-term use. Diuretics often interact unfavorably with many of the drugs elderly patients are likely to be taking (2). Elderly patients receiving digitalis and a diuretic are at increased risk for ventricular arrhythmias and sudden death (2). Since intravascular volume tends to be contracted in the elderly, diuretics also may produce dehydration and, consequently, orthostatic hypotension (3). Beta blockers are effective in elderly patients perhaps related to the reduced beta receptor sensitivity and renin activity of aging (2). Beta blockers may also reduce high-density lipoprotein (HDL) levels (4) and increase insulin resistance (2,5) during long-term use. Beta blockers may cause lethargy, depression, sexual dysfunction, and cold extremities (2). Sympatholytic agents, such as methyldopa and donidine, are often less well tolerated by older patients. CNS and hemodynamic side effects of depression, orthostatic hypotension, and sexual dysfunction may occur more often in elderly hypertensive patients (2). Newer classes of antihypertensive drugs, notably calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEIs), are often recommended for initial therapy in elderly hypertensives (6). These agents offer hemodynamic advantages for elderly patients as well as fewer metabolic or CNS side effects. The new second generation of CCBs, primarily dihydropyridines, appears to offer additional advantages for use in elderly patients. In this paper the pharmacokinetics, clinical efficacy, and tolerability of felodipine, a vasculoselective CCB, are reviewed, with special focus on its use in the elderly.