enalapril and Hypotension--Orthostatic

To compare the effect of enalapril with long-acting nifedipine on orthostatic hypotension in older patients.. A prospective, double blinded, cross-over study.. The outpatient clinic of a university hospital.. Thirty-nine patients aged 65 years or older with systolic blood pressure (SBP) of 140-190 mm Hg and diastolic blood pressure (DBP) of 90-110 mm Hg.. Enalapril 5-20 mg od or nifedipine 30-90 mg od for 8 weeks, followed by 4 weeks washout and cross-over for a second 8-week period.. Supine and standing 0-, 1-, and 5-minutes blood pressure was recorded before and at the end of each treatment period.. At baseline, SBP was 158.8 +/- 8.7 mm Hg, and DBP was 97.1 +/- 5.9 mm Hg. There was a decline in SBP of 6.1 +/- 2.7 mm Hg and 8.4 +/- 4.1 mm Hg after 1 and 5 minutes of standing, respectively. Both agents caused a significant decline in supine blood pressure. Enalapril: supine SBP 158.8 +/- 8.7 to 143 +/- 7.3 mm Hg; supine DBP 97.1 +/- 5.9 to 85.1 +/- 5.1 mm Hg (P = .0001). The drop in SBP after standing for 5 minutes was only 2.4 +/- 1.6 mm Hg with no change in diastolic values. A > or = 10 mm Hg drop in SBP was observed in only three patients, and no patient experienced a decline of 20 mm Hg or more. Nifedipine: supine SBP: 160.3 +/- 9 to 145.3 +/- 8.1 mm Hg; supine DBP: 96.3 +/- 5.7 to 86.3 +/- 5.8 (P = .0001). Nifedipine induced an orthostatic decline in SBP values; there was an 8.7 +/- 4.8 mm Hg difference between supine and 5 minutes standing values (P = .0005) without change in diastolic values. An orthostatic decline in SBP of > or = 10 mm Hg occurred in 13 patients, and there was a drop of > or = 20 mm Hg in six patients. The cross-over of enalapril and nifedipine reproduced the hypotensive effect and reversed the postural effect. (P = .0002 nifedipine vs enalapril). Enalapril and nifedipine were equipotent in reducing supine blood pressure levels. Enalapril also reduced the number of orthostatic episodes significantly, whereas nifedipine aggravated this phenomenon.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Enalapril; Humans; Hypertension; Hypotension, Orthostatic; Nifedipine; Prospective Studies

An examination of the literature provides the basis for a definition of first dose iatrogenic hypotension or "first dose syndrome", its nature, degree and frequency. The drugs that often cause this phenomenon are listed with details of the mechanisms involved as are the physiological, pathological and iatrogenic conditions that may trigger and/or exacerbate the gravity and duration of the syndrome. In a series of patients with essential arterial hypertension treated with ACE inhibitors, 6 developed first dose syndrome, two of them after captopril and 4 after enalapril maleate, two of whom were also receiving theophylline and nitro derivates. Though wide personal experience suggests that first dose syndrome caused by ACE inhibitors is a rare event and those drugs are undeniably effective and well tolerated, treatment should always start with minimum doses administered before bed time especially in patients receiving other medication and/or presenting the physiological or pathological conditions in which first dose syndrome has already been observed and described.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Syndrome; Theophylline

Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.

Topics: Administration, Oral; Aged; Chronic Disease; Dipeptides; Enalapril; Female; Heart Failure; Hemodynamics; Humans; Hypotension, Orthostatic; Long-Term Care; Male; Middle Aged; Oligopeptides; Saralasin; Teprotide; Time Factors