Antihypertensive Agents In Patients Research Articles

Systemic and renal effects of a new angiotensin converting enzyme inhibitor, benazepril, in essential hypertension

Seventeen essential hypertensive patients with normal renal function were treated with a new non-sulphydryl orally active angiotensin converting enzyme (ACE) inhibitor, benazepril, 10 mg given once or twice daily, according to diastolic blood pressure levels, for 6 weeks. In all patients, changes in blood pressure, systemic and renal hemodynamics, plasma renin activity and urinary aldosterone and albumin excretions were assessed at the end of a 2-week placebo run-in period and at the end of the study. Benazepril monotherapy controlled blood pressure well. No changes in cardiac output, heart rate or stroke volume were observed, while peripheral vascular resistance was significantly decreased (-11%, P less than 0.05). Plasma volume was unaltered. The glomerular filtration rate was stable, but effective renal plasma flow was increased because of the marked reduction in renal vascular resistance (-35%) and, therefore, the filtration fraction was decreased. Urinary albumin excretion remained unchanged. A significant increase in plasma renin activity (P less than 0.001) and a decrease in urinary aldosterone excretion were seen. No side effects were observed during the treatment period. In conclusion, our results suggest that benazepril alone is an effective antihypertensive agent in patients with essential hypertension. The blood pressure lowering effect is due mainly to systemic vasodilation and is observed up to 24 h after administration of the drug. The vasodilation appears to be more consistent in the renal than in the systemic circulation.

General considerations in selecting antihypertensive agents in patients with type II diabetes mellitus and hypertension

The Working Group on Hypertension in Diabetes recommends starting pharmacologic treatment of hypertension with a small dose of a thiazide, beta-blocker, prazosin hydrochloride, angiotensin-converting enzyme inhibitor, or calcium channel blocker. Thus, these alternatives are regarded as first-line treatment in hypertensive patients with diabetes mellitus. Both thiazides and beta-blockers can cause deterioration in glycemic control and have an unfavorable influence on the lipoprotein profile. These metabolic side effects may partly counteract beneficial effects. Non-selective beta-blockers should probably be avoided in diabetic patients, since blockade of the beta-2 receptor may be associated with a compromise in peripheral blood flow and with problems associated with hypoglycemia. Cardioselective beta-blockers, which may have primary preventive effects on coronary disease, are beneficial in this patient group. In patients with non-insulin-dependent diabetes mellitus without nephropathy or overt fluid retention, diuretic therapy could be replaced by sodium restriction and/or calcium channel blocker therapy, since these agents also have a mild diuretic effect. Calcium channel blockers, angiotensin-converting enzyme inhibitors, and prazosin hydrochloride have minimal metabolic side effects, making them suitable for treatment of hypertension in this patient group.

Calcium metabolism, calcium-channel blocking agents, and hypertension management.

Increasing evidence has suggested that a disturbance of cellular calcium metabolism may have a role in initiating and maintaining elevated systemic vascular resistance in essential hypertension. Controversy exists over whether calcium can alleviate or exacerbate the hypertensive process, and diversity of calcium metabolism in hypertensive patients has been proposed. Calcium-channel blocking agents are potent vasodilators capable of correcting the elevated systemic vascular resistance. Clinical studies have shown that these drugs have antihypertensive efficacy comparable to established agents. The elderly, blacks, and patients with low renin activity respond well to calcium-channel blockers. These drugs may also offer potential advantages over established antihypertensive agents in patients with other coexisting diseases. Sustained release formulations have been developed, and initial experience with long-term efficacy and tolerability is encouraging. The calcium-channel blockers may become first-line therapy for treatment of hypertension in selected patients.

Captopril in patients with type II diabetes and renal insufficiency: Systemic and renal hemodynamic alterations

Purpose: To our knowledge, clinical studies on the long-term use of angiotensin converting enzyme inhibitors in patients with type II diabetes mellitus and nephropathy with incipient renal failure are nonexistent. We therefore assessed the effects of long-term treatment with captopril on systemic and renal hemodynamics and urinary protein excretion in patients with type II diabetes mellitus and the clinical syndrome of diabetic nephropathy. Patients and methods: Twelve patients, 10 men and two women, with an average age of 52 years (range, 40 to 66), participated in the study. After the basal hemodynamic evaluation, the patients received captopril in two daily doses. The dosage was adjusted at weekly intervals in order to obtain normalization of blood pressure without exceeding the maximum allowable dosage. Four patients also received furosemide (20 to 40 mg/day). Results: After six months of treatment, the intra-arterial blood pressure fell (from 162 ± 17 103 ± 5 to 139 ± 26 89 ± 10 mm Hg) due to the reduction in total peripheral vascular resistance index (from 3,720 ± 658 to 3,190 ± 762 dynes/second/cm −5/m 2), with no change in cardiac index (2.78 ± 0.36 to 2.79 ± 0.47 liters/minute/m 2). No significant change was seen in renal vascular resistance (from 30,175 ± 5,371 to 30,173 ± 5,372 dynes/second/cm −5/1.73 m 2) and in filtration fraction (from 26 ± 8 to 27 ± 10 percent). A slight, not significant, decrease in renal plasma flow (from 243 ± 97 to 217 ± 108 ml/minute/1.73 m 2), in glomerular filtration rate (from 57 ± 17 to 51 ± 19 ml/minute/1.73 m 2), and in proteinuria (from 4.50 ± 3.10 to 3.40 ± 2.31 g/day) was also observed. Conclusion: Our findings suggest that captopril is an effective antihypertensive agent in patients with diabetic nephropathy, but the renal beneficial effects seem to be limited when this syndrome is complicated by renal insufficiency.

Prolonged Calcium Channel Blocker Therapy of Hypertension

The dihydropyridine calcium channel blocker nitrendipine was studied in 329 hypertensive patients at 12 separate centers for periods of 1 year or more. Patients with untreated supine diastolic blood pressures greater than 90 mm Hg were given nitrendipine 5 mg twice daily for 1 week; if the goal blood pressure was not achieved (supine diastolic blood pressure less than 90 mm Hg with a fall of at least 10 mm Hg), the dose was doubled, and if necessary it was doubled again after an additional week. By the end of titration, the goal blood pressure had been achieved in 138 patients (44%). During the subsequent 11 months of study, 155 patients continued to take nitrendipine alone; their posttitration supine diastolic blood pressure was 85 +/- 7 mm Hg, and at the end of the 1 year study it was 84 +/- 6 mm Hg. There were no significant changes in body weight or in heart rate. At their discretion, investigators could add other antihypertensive agents in patients not responding adequately to nitrendipine alone. In 41 patients with a supine diastolic blood pressure of 95 +/- 9 mm Hg after initial titration, propranolol was added to the nitrendipine and decreased the supine diastolic blood pressure to 88 +/- 8 mm Hg by the end of the study; and in another 76 patients with a posttitration supine diastolic blood pressure of 92 +/- 7 mm Hg, the addition of hydrochlorothiazide decreased the supine diastolic blood pressure to 86 +/- 7 mm Hg by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous Oxide for Blood Pressure Control after Coronary Artery Surgery: A Dose-Response Hemodynamic Study in Postoperative Patients

The inhaled anesthetic nitrous oxide is used for sedation in the coronary care unit and has been advocated as an antihypertensive agent in patients after a cardiac operation. To delineate the hemodynamic effects of nitrous oxide after cardiac surgery, we studied 11 patients with a mean age of 63 years who had undergone isolated coronary artery bypass grafting. All patients had major coronary artery disease and normal preoperative hemodynamic function. When patients were in stable condition in the intensive care unit, hemodynamic measurements were made at an inspired oxygen concentration of 40% with progressive doses of nitrous oxide (0, 10, 20, 40, and 60%). Measured and calculated hemodynamic data were compared using analysis of variance. Nitrous oxide caused significant decreases in mean arterial pressure in a dose-related fashion; pressure fell 6 mm Hg at 10% nitrous oxide and 11 mm Hg at 60% nitrous oxide (6 and 13% decreases). These changes were not associated with significant alteration in pulmonary artery pressure or cardiac index. Left ventricular stroke work index decreased significantly with the administration of nitrous oxide. We conclude that, in patients with normal hemodynamic and ventricular function, the administration of nitrous oxide for its sedative and antihypertensive effects is safe in the postoperative period and may be useful, especially in patients who are candidates for early extubation.

Antihypertensive Effects and Pharmacokinetics of Single and Consecutive Administration of Doxazosin in Patients with Mild to Moderate Essential Hypertension

A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once daily (o.d.) for evaluation of its consecutive dosing effect. The antihypertensive effect, pharmacokinetics, and effects on the plasma renin activity (PRA) of doxazosin were investigated. Following a 2-mg single dose of doxazosin, the systolic blood pressure (SBP) decreased significantly up to 12 h, whereas consecutive dosing produced a significant decrease in the SBP up to 24 h and a significant decrease in the mean blood pressure up to 24 h as compared with placebo. The pharmacokinetic parameters of doxazosin in both single- and consecutive-dose study were 18.9 and 25.8 ng/ml in Cmax, 11.1 and 12.9 h in half life (t1/2), and 182.0 and 273.0 ng h/ml in area under the curve (AUC)24(0), respectively. No significant changes were observed in PRA and plasma concentration of catecholamines. Neither were there any observable changes in endogenous creatinine clearance and in the urinary excretion rates of Na, K, and Cl. Doxazosin was well tolerated by all patients, and no untoward effects were observed. Doxazosin effectively reduces blood pressure and, because of its long t1/2 and minimal effects on PRA catecholamines, and electrolytes, seems to be a useful antihypertensive agent in patients with essential hypertension.

Alacepril: is a potent antihypertensive agent in patients with slightly elevated BP

Alacepril: is a potent antihypertensive agent in patients with slightly elevated BP

I. Implications of recent clinical trials in systemic hypertension II. Results of a multicenter trial of nitrendipine, for mild to moderately severe systemic hypertension

Results of the European Working Party group study and the Medical Research Council clinical trial in mild hypertension have important implications for the practicing physician. They appear to confirm 2 previous impressions. The first is that therapy for elderly patients with both systolic and diastolic hypertension is beneficial; cardiovascular mortality can be reduced by lowering blood pressure. These data are consistent with the findings in the 60- to 69-year-old cohort in the Hypertension Detection and Follow-up Program study in the US. The second is that specific treatment with antihypertensive agents in patients with mild hypertension will decrease overall cardiovascular mortality compared with placebo treatment. The approach to treatment in both of these studies was relatively simple, using a diuretic as step 1 therapy in the European study, and either a diuretic or a β-adrenergic inhibiting agent in the Medical Research Council study. These data provide further evidence for the benefits of treatment of hypertension.

Fetal distress after hydralazine therapy for severe pregnancy-induced hypertension.

Hydralazine is the most commonly used antihypertensive agent for patients with severe toxemic states. Its use, however, can produce hypotension and acute uteroplacental insufficiency, resulting in fetal distress. Our review of hospital charts of severely preeclamptic or eclamptic patients observed during a two-year period showed that 24 of 77 patients were treated with hydralazine; the remainder were not. Of those receiving hydralazine, 38% (9/24) were delivered by cesarean section because of fetal distress, as compared to 9% (5/53) of those not receiving hydralazine (P less than .01). Of patients whose hydralazine therapy was inappropriate, 82% (9/11) incurred fetal distress versus 38% (5/13) when hydralazine was appropriately administered (P less than .05). In patients receiving hydralazine, fetal distress is in part the consequence of the severity of the disease, but excess use of antihypertensive agents appears to increase this risk.

Use of antihypertensive agents in patients with glucose intolerance

The selection, use, and potential adverse effects of antihypertensive agents in patients with glucose intolerance are reviewed. Thiazide diuretics frequently impair glucose tolerance, but this deterioration is usually modest and should not preclude use of these agents in most patients with glucose intolerance. The loop diuretics furosemide and ethacrynic acid have also been associated with decreased glucose tolerance. The beta-adrenergic blocking agents may inhibit insulin secretion, but few patients will experience clinically important elevations in blood glucose. Rather than producing glucose intolerance, these agents may delay recovery from hypoglycemic episodes and may mask catecholamine-induced symptoms of hypoglycemia. In certain cases, use of cardioselective beta blockers or avoidance of beta-blocker therapy may be indicated, especially in insulin-dependent diabetics. The calcium-channel blocking agents nifedipine and verapamil have been reported to produce diabetogenic effects in a few studies, but further investigations are needed to define the extent of these effects. Available evidence indicates that sympatholytic agents such as guanethidine and reserpine, alpha 2-adrenergic agonists such as methyldopa and clonidine, the alpha 1-blocking agent prazosin, and the vasodilators captopril and hydralazine produce few, if any, clinically important changes in glucose tolerance. While no antihypertensive agents are absolutely contraindicated in patients with glucose intolerance, patients with glucose intolerance who are receiving thiazide diuretics, beta blockers, and calcium-channel blocking agents should be monitored with extra care for hyperglycemia or deterioration in glucose tolerance.

Labetalol infusion for the treatment of hypertension in acute myocardial infarction.

The haemodynamic effects of labetalol infusion (mean dose 1 mg/min) were measured in seven patients with sustained hypertension complicating acute myocardial infarction. Four of the patients had severe left ventricular failure. A fall in both systolic (mean 185 to 126 mm Hg) and diastolic (mean 87 to 68 mm Hg) blood pressure occurred in all patients. Cardiac index fell from 2.5 to 2.0 l/min/m2; systemic vascular resistance was not affected. Heart rate slowed from 83 to 70 beats/ min. Labetalol lowered pulmonary artery pressure in the patients with left ventricular failure. Labetalol is an effective antihypertensive agent in patients with acute myocardial infarction and our results suggest it is safe provided cardiac output is within or near the normal range. It seems not to be contraindicated in the presence of pulmonary oedema. The effects imply that myocardial oxygen requirements will be reduced. The implications for limitation of infarct size in patients presenting early after acute infarction should be determined.

Superactive inhibitors of angiotensin converting enzyme: Analogs of BPP 9a containing dehydroproline

FEBS LettersVolume 107, Issue 2 p. 273-276 Full-length articleFree Access Superactive inhibitors of angiotensin converting enzyme Analogs of BPP9a containing dehydroproline George H. Fisher, George H. Fisher Department of Medicine (D58), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USASearch for more papers by this authorJames W. Ryan, James W. Ryan Department of Medicine (D58), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USASearch for more papers by this author George H. Fisher, George H. Fisher Department of Medicine (D58), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USASearch for more papers by this authorJames W. Ryan, James W. Ryan Department of Medicine (D58), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USASearch for more papers by this author First published: November 15, 1979 https://doi.org/10.1016/0014-5793(79)80388-9Citations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 A.V. Robertson, B. Witkop, J. Am. Chem. Soc., 84, (1962), 1697– 1701. 2 S.H. Ferreira, D.C. Bartelt, L.J. Greene, Biochemistry, 9, (1970), 2583– 2593. 3 M.A. Ondetti, N.J. Williams, E.F. Sabo, J. Pluscec, E.R. Weaver, O. Kocy, Biochemistry, 10, (1971), 4033– 4039. 4 Y.S. Bakhle, I.H. Page F.M. Bumpus Handbook of Experimental Pharmacology (1974), Springer-Verlag Berlin 41– 80. 5 F.E. Dorer, J.R. Kahn, K.E. Lentz, M. Levine, L.T. Skeggs, Circ. Res., 34, (1974), 824– 827. 6 H. Gavras, H.R. Brunner, J.H. Laragh, J.E. Sealey, I. Gavras, R.A. Vukovich, New Engl. J. Med., 291, (1974), 817– 821. 7 H. Gavras, H.R. Brunner, J.H. Laragh, I. Gavras, R.A. Vukovich, Clin. Sci. Mol. Med., 48, (1975), 57S– 60S. 8 D.B. Case, J.M. Wallace, H.J. Keim, M.A. Weber, J.I. Drayer, R.P. White, J.E. Sealey, J.H. Laragh, Am. J. Med., 61, (1976), 790– 796. 9 D.B. Case, J.M. Wallace, H.J. Keim, M.A. Weber, J.E. Sealey, J.H. Laragh, New Engl. J. Med., 296, (1977), 641– 646. 10 L.T. Skeggs, J.R. Kahn, N.P. Shumway, J. Exp. Med., 103, (1956), 295– 299. 11 K.K.F. Ng, J.R. Vane, Nature, 216, (1967), 762– 766. K.K.F. Ng, J.R. Vane, Nature, 218, (1968), 144– 150. 12 A.M. Felix, C.-T. Wang, A.A. Leibman, C.M. Delaney, T. Mowles, B.A. Burghardt, A.M. Charnecki, J. Meienhofer, Int. J. Pept. Prot. Res., 10, (1977), 299– 310. 13 G.H. Fisher, D.I. Marlborough, J.W. Ryan, A.M. Felix, Arch. Biochem. Biophys., 189, (1978), 81– 85. 14 G.R. Marshall, N. Back L. Martini R. Paolett Pharmacology of Hormonal Polypeptides and Proteins (1968), Plenum New York 48– 52. 15 B.F. Gisin, R.B. Merrifield, J. Am. Chem. Soc., 94, (1972), 3102– 3106. 16 J.W. Ryan, A. Chung, L.C. Martin, U.S. Ryan, Tissue Cell, 10, (1978), 555– 563. 17 M.A. Ondetti, B. Rubin, D.W. Cushman, Science, 196, (1977), 441– 444. 18 D.W. Cushman, H.S. Cheung, E.F. Sabo, M.A. Ondetti, Biochemistry, 16, (1977), 5484– 5491. 19 G.H. Fisher, J.W. Ryan, L.C. Martin, G. Pena, Adv. Exp. Med. Biol., (1979), in press 20 D.W. Cushman, J. Plusece, N.J. Williams, E.R. Weaver, E.F. Sabo, O. Kocy, H.S. Cheung, M.A. Ondetti, Experientia, 29, (1973), 1032– 1034. 21 S. Moore, A.M. Felix, J. Meienhofer, C.W. Smith, R. Walter, J. Med. Chem., 20, (1977), 495– 500. 22 D.I. Marlborough, J.W. Ryan, A.M. Felix, Arch. Biochem. Biophys., 176, (1976), 582– 590. Citing Literature Volume107, Issue2November 15, 1979Pages 273-276 ReferencesRelatedInformation

Chronic Hemodynamic Effects of Propranolol Treatment in Dialysis-Refractory Hypertension

The hemodynamic mechanism of the hypotensive effect of propranolol was studied by quantitative radiocardiography in 8 patients with dialysis-resistant hypertension. Propranolol treatment brought about a decrease in mean arterial pressure and peripheral vascular resistances. The cardiac index was slightly reduced only in the early stage of the treatment. No significant difference was found between patients on treatments lasting longer than 3 months and patients with dialysis-controlled hypertension. The results show that propranolol can be used safely as the sole antihypertensive agent in patients with dialysis-resistant hypertension.

Rapid GLC determination of fusaric acid in biological fluids.

A simple, sensitive GLC assay was developed for fusaric acid, the active metabolite of bupicomide, to follow the disposition of this investigational antihypertensive agent in patients undergoing therapy. Fusaric acid is efficiently extracted from biological samples, derivatized by on-column methylation, and chromatographed using flame-ionization detection. An internal standard is utilized to quantitate results. The procedure is rapid and specific for fusaric acid, and has a lower limit of sensitivity of 0.1 mug/ml. The method is suitable for supporting pharmacokinetic studies of bupicomide following therapeutic doses in animals and humans.

Pharmacologic Management of Renovascular Hypertension

To determine the response that might be expected when renovascular hypertension is managed pharmacologically, the records of 24 patients, whose conditions were subsequently cured or improved by surgery, were examined. Mean diastolic pressure fell from 128 to 106 mm Hg, with an average of two antihypertensive agents in patients with fibromuscular hyperplasia, while an average of three agents was required to lower mean diastolic pressure, from 127 to 107 mm Hg, in patients with atherosclerotic lesions. Blood pressure elevation in fibromuscular hyperplasia is more responsive to antihypertensive agents than it is in patients with atherosclerotic lesions causing hypertension of equal severity.

Future trends in antihypertensive therapy.

SummaryAn attempt was made to replace the more conventional approach to antihypertensive therapy (cuff approach) by antihypertensive therapy based on physiopathological findings (physiopathological approach). The use of beta adrenergic blocking agents in hypertensive patients with high cardiac output and of peripheral vasodilating antihypertensive agents in patients with increased total peripheral resistance was discussed. Sodium depletion by diuretics and low sodium diet was advised in high plasma volume types of hypertension, but also in other hypertensive patients. The possibilities of a more specific antihypertensive therapy in patients with low and high plasma renin levels was assessed. The importance of a prognostic approach in the treatment of hypertensive patients was stressed.