المؤلفون: Kevin D. Ballard, Sarat Sunthornyothin, James L. Pool, Roberto Mangoo-Karim, Robert R. Luther, Addison A. Taylor, William Polvino, Alexander M. M. Shepherd

المصدر: American Journal of Hypertension. 12:906-914

مصطلحات موضوعية: Adult, Male, Time Factors, Adolescent, Fenoldopam, Diastole, Blood Pressure, Essential hypertension, Double-Blind Method, Pharmacokinetics, Heart Rate, Infusion Procedure, Heart rate, Internal Medicine, medicine, Humans, Infusions, Intravenous, Aged, business.industry, Benzazepines, Blood Pressure Monitoring, Ambulatory, Middle Aged, medicine.disease, Treatment Outcome, Blood pressure, Anesthesia, Pharmacodynamics, Dopamine Agonists, Hypertension, Female, business, Half-Life, medicine.drug

الوصف: Thirty-three patients with mild-to-moderate essential hypertension received either placebo or fenoldopam, a selective dopamine-1 agonist, by intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 μg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h drug infusion. Plasma concentrations of racemic fenoldopam were measured at frequent intervals during and for 24 h after fenoldopam infusion. In the 26 patients who received fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied ( − 9 and − 9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 μg/kg/min, P .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving fenoldopam at 0.8 μg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the drug developed slowly during the 48 h of drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate hypertension at doses as low as 0.04 μg/kg/min, is well tolerated at doses up to 0.8 μg/kg/min, maintains most of its antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound hypertension when discontinued. The pharmacodynamic effects of the drug are best predicted by pharmacokinetics of racemic and R-fenoldopam.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::450aa5d4f3ccfdcaa1e4d714729bda57Test
https://doi.org/10.1016/s0895-7061Test(99)00068-0

المؤلفون: Deanna G. Cheung, Michael A. Weber, Robert R. Luther, Atul Laddu

المصدر: American Heart Journal. 122:905-910

مصطلحات موضوعية: Male, Supine position, Ambulatory blood pressure, Blood Pressure, Essential hypertension, Placebo, Drug Administration Schedule, law.invention, Terazosin, Randomized controlled trial, law, medicine, Humans, Dosing, Adrenergic alpha-Antagonists, Antihypertensive Agents, Dose-Response Relationship, Drug, business.industry, Prazosin, Middle Aged, medicine.disease, Blood Pressure Monitors, Blood pressure, Anesthesia, Hypertension, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug

الوصف: Terazosin is a selective alpha 1-adrenergic-blocking agent indicated for the treatment of hypertension. The aim of this multicenter study, performed in 256 patients with mild to moderate essential hypertension, was to define the dosing characteristics of terazosin (in the range of 1 to 80 mg) administered once daily. Patients were randomly assigned to placebo or active treatment groups; each group received 3 months of treatment, which comprised three ascending doses of terazosin, each administered for a 1-month period. As determined by conventional office measurements of supine diastolic blood pressure and by automated ambulatory blood pressure monitoring, there was a clear antihypertensive dose-response relationship for terazosin in the range of 1 to 5 mg daily. Except for the 80 mg dose, none of the doses above 5 mg (10 to 40 mg) appeared to provide additional efficacy. Both the office measurements and the monitoring data indicated that the ratio of trough (effect at the end of the dosing interval) to peak (maximum effect during the dosing interval) was at least 50% or greater during treatment with the 5 mg dose. Thus the 5 mg dose appeared to provide meaningful clinical antihypertensive efficacy and to sustain its effects throughout the full 24-hour period.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02974bac44648732ba14a717f4bebdc6Test
https://doi.org/10.1016/0002-8703Test(91)90810-5

المؤلفون: Pamela W. Anderson, Willa A. Hsueh, Morris Schambelan, Yung S. Do, Robert S. Boger, Richard Horton, Robert R. Luther

المصدر: The American Journal of Cardiology. 66:1342-1347

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Prostacyclin, Essential hypertension, Plasma renin activity, Excretion, chemistry.chemical_compound, Internal medicine, Renin, Renin–angiotensin system, medicine, Humans, Aldosterone, business.industry, Dipeptides, Middle Aged, medicine.disease, Epoprostenol, Endocrinology, Blood pressure, chemistry, Hypertension, Female, Diuretic, Cardiology and Cardiovascular Medicine, business, medicine.drug

الوصف: The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ba02b991293f929937b4dbf9e204adaeTest
https://doi.org/10.1016/0002-9149Test(90)91165-3

المؤلفون: Irene Gavras, Michael Bursztyn, Charles P. Tifft, Robert R. Luther, Haralambos Gavras, Robert S. Boger

المصدر: Journal of cardiovascular pharmacology. 15(3)

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Captopril, medicine.drug_class, Hemodynamics, Blood Pressure, Essential hypertension, Plasma renin activity, Renin inhibitor, Internal medicine, Renin–angiotensin system, Renin, Medicine, Humans, Pulse, Pharmacology, biology, business.industry, Dipeptides, Middle Aged, medicine.disease, Endocrinology, Blood pressure, Enzyme inhibitor, Pathophysiology of hypertension, Creatinine, Hypertension, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, Blood Chemical Analysis

الوصف: The effects of A-64662, a new specific renin inhibitor, on plasma renin activity (PRA) and blood pressure (BP) were studied for the first time in patients with essential hypertension. A single intravenous bolus of vehicle, 0.001, 0.003, 0.01, 0.03, and 0.1 mg/kg was given to the first four patients, maintained on a constant 100 mEq Na diet. PRA was promptly reduced from 3.4 +/- 2.9 (mean +/- SEM) to 0.2 +/- 0.06 ng/ml/h, a 94% inhibition with the smallest dose, and to undetectable levels (less than 0.1 ng/ml/h) with the larger ones. However, BP did not change within this dose range. The subsequent seven patients received larger doses ranging from 0.2 to 1.0 mg/kg. In three cases, there was reduction in BP on the second dosing day, at doses of 0.4, 0.7, and 1 mg/kg. All responses were late (at 110 min after the injection), transient, and unrelated to baseline PRA. These results strongly suggest that there is a dissociation between the effectiveness of A-64662 in inhibiting PRA and its blood pressure lowering effect in hypertensive patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f9d0259529a15a4defbba3c0659798d2Test
https://pubmed.ncbi.nlm.nih.gov/1691375Test

المؤلفون: Peter J. Schmitz, Harriet N. Glassman, Jennifer K. Horton, Robert R. Luther, Charles B. Estep, David G. Jordan

المصدر: American Journal of Hypertension. 1:237S-240S

مصطلحات موضوعية: Adult, Male, Time Factors, Supine position, medicine.drug_class, Blood Pressure, Nasal congestion, Essential hypertension, Terazosin, Internal Medicine, medicine, Humans, Pulse, Adverse effect, Beta blocker, Adrenergic alpha-Antagonists, Aged, business.industry, Body Weight, Prazosin, Middle Aged, medicine.disease, Hypokalemia, Blood pressure, Anesthesia, Hypertension, Female, medicine.symptom, business, medicine.drug

الوصف: The long-term treatment of essential hypertension with terazosin, a new once-a-day alpha 1-adrenergic blocking agent, was evaluated in 364 hypertensive patients who received total daily doses of 1 to 40 mg for 3 weeks to 56 months. Consistent mean decreases in supine and standing systolic and diastolic blood pressures were observed throughout the study for patients treated with terazosin as monotherapy (supine, 9 to 12/10 to 13 mm Hg; and standing, 12 to 18/11 to 14 mm Hg) or in combination with other antihypertensive agents (supine, 12 to 16/12 to 15 mm Hg; and standing, 16 to 22/13 to 19 mm Hg). The most commonly reported adverse experiences were dizziness, headache, asthenia, cold symptoms, and nasal congestion. Adverse effects and metabolic disorders often associated with diuretics and beta blockers such as sexual dysfunction, hyperglycemia, hyperuricemia, hypokalemia, or adverse lipid effects were seen infrequently during long-term treatment with terazosin as monotherapy. Overall, terazosin was shown to be effective, safe, and well tolerated by most patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ccf11fe7f56a2e12676df13eb7e636b6Test
https://doi.org/10.1093/ajh/1.3.237sTest

المؤلفون: Robert R. Luther

المصدر: American Journal of Hypertension. 2:729-735

مصطلحات موضوعية: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Alpha (ethology), Left ventricular hypertrophy, medicine.disease, Essential hypertension, Terazosin, medicine.anatomical_structure, Blood pressure, Internal medicine, Internal Medicine, medicine, Prazosin, Cardiology, Vascular resistance, Lipid profile, business, medicine.drug

الوصف: Selective alpha 1 adrenergic receptor blocking agents lower blood pressure by reducing the increased peripheral vascular resistance that characterizes essential hypertension. Prazosin and terazosin have been shown to be well tolerated in clinical practice and seldom cause impotence or metabolic abnormalities. The most common adverse effects--dizziness, headache, and asthenia--are generally well tolerated and infrequently lead to discontinuation of therapy. First-dose syncope can usually be avoided by initiating therapy with low doses administered at bedtime. Finally, the alpha 1 receptor antagonists do not adversely affect such cardiovascular risk factors as hypokalemia, serum lipid profile, and left ventricular hypertrophy. In fact, alpha 1 antagonists reduce total cholesterol and low-density-lipoprotein plus very-low-density-lipoprotein cholesterol and thus may contribute to the overall management of cardiovascular risk by blood pressure reduction and improvement of the serum lipid profile. Since the goal of treating chronic essential hypertension is to improve morbidity and mortality, the choice of therapy should be influenced by the agent's ability to modify as many risk factors as possible. Alpha 1 adrenoreceptor antagonists beneficially impact several cardiovascular risk factors and thus merit consideration as first-line antihypertensive therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6554f528e1c62b5de20cd7a248d052f4Test
https://doi.org/10.1093/ajh/2.9.729Test

المؤلفون: Harriet N. Glassman, W.David Sperzel, David C. Jordan, Robert R. Luther

المصدر: The American journal of medicine. 80(5B)

مصطلحات موضوعية: Adult, Male, Supine position, Adolescent, Hematocrit, Placebo, Essential hypertension, Dizziness, Piperazines, Syncope, Terazosin, White blood cell, medicine, Prazosin, Humans, Pulse, Adrenergic alpha-Antagonists, Aged, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Body Weight, Headache, General Medicine, Middle Aged, medicine.disease, medicine.anatomical_structure, Anesthesia, Asthenia, Hypertension, Female, business, medicine.drug

الوصف: The safety of terazosin, an effective agent for the treatment of hypertension, was assessed by analyzing data from 1,006 hypertensive patients who were enrolled in short-term and/or long-term studies. The total experience with terazosin in this article represents 422.5 patient-years. Changes in pulse rate measurements from pretreatment to posttreatment were not significantly different between the terazosin- and placebo-treated patients (-1.0 beat per minute for the terazosin group and -1.0 beat per minute for the placebo group, in the supine position). Dizziness, headache, and asthenia were the most commonly reported adverse experiences among all terazosin-treated patients, although the incidence of headache in placebo-controlled trials was not significantly different between the terazosin and placebo groups. As a whole, patients receiving terazosin had a tendency to gain small amounts of weight (2 pounds). In addition, there was a trend for slight decreases in hemoglobin, hematocrit, white blood cell count, total protein, and albumin levels in those patients who received terazosin, suggesting hemodilution. Overall, terazosin was shown to be safe in patients with mild to moderate essential hypertension.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52eca28f54fae1bdfe405e8cd42e8a6bTest
https://pubmed.ncbi.nlm.nih.gov/2872812Test