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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 145 records · Page 8Linked to original sources
PubMed1989

Dilevalol compared with propranolol and placebo for systemic hypertension.

Dilevalol is a new antihypertensive agent that is both a vasodilator, through its beta 2-agonist action, and a nonselective beta antagonist. Two multicenter, double-blind studies were performed: study 1 compared dilevalol administered once-daily with either dilevalol or propranolol every 12 hours; study 2 compared dilevalol administered once daily with placebo. Both studies had a placebo run-in period to establish that the baseline supine diastolic blood pressures were consistent in the mild to moderate severity range (95 to 115 mm Hg) at 2 consecutive visits for study 1 and in the mild severity range (95 to 105 mm Hg) in study 2. Patients then were randomized to the double-blind titration phase, during which doses were titrated over a 9-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg and a decrease from baseline of greater than or equal to 10 mm Hg. Patients were then maintained on a fixed dose for 2 months (study 1) or for 1 month (study 2). Dilevalol given once daily was as effective in reducing supine diastolic blood pressure as dilevalol every 12 hours and propranolol every 12 hours (study 1) and was superior to placebo (p less than 0.001) (study 2). In both studies, dilevalol given once daily was effective and well tolerated. The side-effect profile of dilevalol was similar to that of placebo and different from that of propranolol. Treatment with dilevalol resulted in significantly less fatigue (p less than 0.05), bradycardia (less than 50 beats/minute) and mental depression than with propranolol, but significantly (p less than 0.05) more diarrhea/loose stools.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Effects of dilevalol, metoprolol and atenolol on left ventricular mass and function in nonelderly and elderly hypertensive patients.

Using serial M-mode echocardiographic determinations of left ventricular (LV) mass and function, the effects of dilevalol, a selective beta 2 agonist with nonselective beta-antagonist properties, were compared with those of metoprolol in 2 centers in double-blind, randomized clinical trials using similar protocols in nonelderly hypertensive patients (aged less than 65 years) (study 1). In a separate bicenter study with a similar design, dilevalol was compared with atenolol in elderly hypertensive patients (aged greater than or equal to 65 years) (study 2). Patients in both studies received placebo for 2 to 4 weeks, and were then randomized to receive increasing doses of dilevalol (200, 400, 800, 1,600 mg) or metoprolol (100, 200, 300, 400 mg) in study 1, and dilevalol (100, 200, 400, 800 mg) or atenolol (50, 100 mg) in study 2, to achieve a supine diastolic blood pressure (BP) of less than 90 mm Hg. In both studies, LV function and mass (Penn convention) were determined by echocardiographic examinations performed before randomization and at the end of the active treatment phase. Dilevalol, metoprolol and atenolol significantly reduced BP compared with placebo. In the nonelderly patients, a modest reduction in LV mass was observed with dilevalol (p less than 0.03) but not with metoprolol. Indexes of LV function--as assessed by end-diastolic and end-systolic dimensions, LV ejection time and ejection fraction--were better preserved by dilevalol than by metoprolol. In the elderly, neither dilevalol nor atenolol affected LV mass; however, indexes of LV function were better preserved with dilevalol than with atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Celiprolol in systemic hypertension.

The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.

Antihypertensive Agents↗
PubMed1989

Dilevalol: a selective beta-2 adrenergic agonist vasodilator with beta adrenergic blocking activity.

Dilevalol is the R-R' optical isomer of labetalol and differs pharmacologically from the racemic mixture in the following ways: it is seven-fold more potent as a selective beta-2 agonist; it is four times more potent as a nonselective beta antagonist; it has no clinically significant alpha antagonist property. Dilevalol is a vasodilator and reduces blood pressure by reducing systemic vascular resistance. It has a half-life of 15-18 hours, and is demonstrated to be effective as an antihypertensive agent for 24-30 hours. Hemodynamic studies in humans show that following administration of dilevalol either orally or intravenously, blood pressure falls as a consequence of a decrease in systemic vascular resistance. Cardiac index is unchanged and heart rate decreases slightly. Dilevalol is shown to cause regression of left ventricular hypertrophy in younger individuals, to improve left ventricular performance and to have no effect on parameters of renal function. Prospective double-blinded clinical trials in comparison with placebo, propranolol, metoprolol and atenolol were conducted and demonstrate dilevalol to be an effective antihypertensive agent with a favorable side effect profile with a particularly low incidence of central nervous system side effects.

Animals↗
PubMed1989

Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time.

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1989

New therapeutic modalities in hypertension: focus on a new calcium antagonist-nicardipine.

A new generation of dihydropyridine calcium antagonists which are related structurally to nifedipine is undergoing clinical investigation. Among these newer agents. nicardipine and nimodipine have become available for clinical use. In controlled trials, nicardipine is superior to placebo and equal to other antihypertensive agents for the treatment of systemic hypertension. Nicardipine is associated with a low incidence of adverse effects that are related primarily to its peripheral vasodilatory actions. In addition, nicardipine appears to have little if any negative effects on myocardial contractility or conduction.

Humans↗
PubMed1989

Labetalol compared with propranolol in patients with both angina pectoris and systemic hypertension: a double-blind study.

Labetalol is a non-selective beta-adrenoceptor antagonist agent with added alpha 1-adrenergic blocking properties, beta 2-stimulating action, and direct vasodilatory activity. A multi-center, double-blind, parallel group study compared the safety and efficacy of labetalol to propranolol in the treatment of patients with both exertional angina and mild to moderate systemic hypertension. An initial 4 to 5 week placebo washout phase was followed by a five week titration phase and a four month maintenance phase. Labetalol and propranolol had similar effects in reducing supine and standing blood pressures, except for a greater reduction in standing systolic blood pressure seen in the labetalol group. There were comparable effects by both treatments on angina attacks, nitroglycerin use, and exercise tolerance. Adverse effects were frequent with both drugs, but were generally minor. Thus, labetalol appears to be an effective alternative to propranolol in the treatment of patients with coexisting angina pectoris and hypertension, with the choice of agent dependent on the clinical situation.

Adult↗
PubMed1989

Clinical utility of nifedipine and diltiazem plasma levels in patients with angina pectoris receiving monotherapy and combination treatment.

The clinical utility of nifedipine and diltiazem blood levels in patients with angina pectoris receiving monotherapy (N = 14) and combination treatment (N = 9) were assessed in a placebo run-in, double blind, randomized, crossover study. Compared to placebo, diltiazem (mean daily dose 360 mg), nifedipine (mean daily dose 90 mg) and combination diltiazem-nifedipine therapy (mean daily dose 55 mg of nifedipine, 360 mg of diltiazem) were associated with reductions in weekly angina attacks and nitroglycerin consumption. Although both drugs used as monotherapy and in combination were also associated with significant increments in exercise tolerance and other improved angina parameters, these changes were not related to the plasma levels of either drug. Nifedipine plasma levels were measured by gas chromatography and diltiazem plasma levels measured by reverse high-pressure liquid chromatography from specimens obtained 2-5 hours after the last previous dose, after 1, 2 and 3 weeks of treatment, and during baseline placebo and placebo washout periods. With combination therapy, there was no effect on the diltiazem plasma level compared to monotherapy. The significant decrease in the nifedipine dose in patients on combination therapy did not significantly change nifedipine plasma levels. Determinations of plasma levels of diltiazem and nifedipine in the management of patients is of no value in the management of patients with angina pectoris except for monitoring treatment compliance and overdosage.

Aged↗
PubMed1989

The use of inotropic agents in acute and chronic congestive heart failure.

This article reviews our current understanding of the physiology of myocardial contraction; recent research into its mechanical, macromolecular, and biochemical foundations; and its role in the clinical syndromes of congestive heart failure. This review serves as a background for discussing the mechanism of action and pharmacology of currently available and experimental inotropic agents. The clinical applications of these drugs are discussed and the successes and failures of the pharmacologic approach to patients with congestive heart failure analyzed.

Acute Disease↗
PubMed1989

Angiotensin-converting enzyme inhibitors in heart failure.

Recognition of the importance of the renin-angiotension-aldosterone system in heart failure, along with an appreciation of the hemodynamic benefits of vasodilator therapy has led to the widespread use of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure. The ACE inhibitors are the only class of vasodilator agents shown to have a significant protective effect against mortality in patients with heart failure.

Aldosterone↗
PubMed1989

Calcium antagonists and heart failure.

The systemic vasodilatory actions of the calcium antagonists make them potentially attractive for use as afterload reducing agents in patients with left ventricular failure. However, unlike other vasodilator drugs, these drugs also exert a direct negative inotropic effect on the myocardium. Clinical data suggest a limited role for the calcium antagonists as vasodilator therapy in patients with heart failure.

Calcium Channel Blockers↗
PubMed1989

Nitrates in congestive heart failure.

An important role for nitrates in the treatment of patients with congestive heart failure has been demonstrated. By dilating the venous and arterial vasculature, they improve hemodynamics as well as exercise tolerance. Attenuation of nitrate action that occurs with chronic therapy can be minimized by following certain treatment strategies.

Heart Failure↗
PubMed1989

Beta-adrenergic blocking drugs in the treatment of congestive heart failure.

Experimental and clinical data suggests that increased serum catecholamines may have predominantly detrimental effects in patients with congestive heart failure. Some investigators have proposed use of beta-blockers in heart failure as a means of ameliorating the harmful effects of the excess catecholamines. The clinical experience to date with use of these agents as therapy in congestive heart failure is limited but does suggest a future role for beta-blockers as adjunct therapy in a select population of patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed1989

Beta-adrenergic blockade and calcium channel blockade in myocardial infarction.

Because of their hemodynamic and antiarrhythmic actions, beta-adrenergic blockers and calcium-entry blockers have been suggested for use in patients with myocardial infarction (MI) for reducing infarct size, preventing ventricular ectopy, and for prolonging life in survivors of acute MI. Experimental studies have suggested their usefulness in these areas. Clinical studies have demonstrated a role for beta-blockers in the hyperacute phase of MI, and in longterm treatment of infarct survivors. Calcium channel blockers appear to have somewhat less utility in patients with Q wave MIs, but may have an important role in therapy of the non-Q wave infarct.

Adrenergic beta-Antagonists↗
PubMed1989

Lovastatin: an HMG-CoA reductase inhibitor for lowering cholesterol.

Increased levels of cholesterol, LDL-cholesterol, and VLDL-cholesterol are known risk factors for the development of coronary artery disease. There are multiple drugs that can be used for lowering cholesterol, including lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme step in cholesterol synthesis in the body. The pharmacology of this novel agent is discussed in this article.

Cholesterol↗
PubMed1989

Cocaine-induced coronary artery disease: recognition and treatment.

Recreational use of cocaine has reached epidemic proportions. Recent reports have linked cocaine use to various acute and chronic cardiovascular disorders. The pharmacology of cocaine is discussed in this article, and the experiences with cocaine-induced coronary artery disease reviewed.

Cardiovascular System↗
PubMed1989

A multicenter double-blind study of the efficacy and safety of once and twice daily dilevalol compared to propranolol.

Dilevalol, the R,R isomer of labetalol, is a non-selective beta-adrenergic blocking drug with vasodilator properties which differ from those of labetalol in that they are attributable to beta-2 agonism rather than alpha-1 blockade. This multicenter, double-blind, randomized study compares the antihypertensive efficacy and safety of dilevalol with propranolol and, in addition, compares the efficacy of dilevalol when given once daily with twice daily. Caucasian patients with mild and moderate essential uncomplicated hypertension were divided into three treatment groups and received either propranolol twice daily (N = 59), dilevalol twice daily (N = 60), or dilevalol once daily (N = 53). Patients were given increasing doses of these medications over a 2 to 10 week period to achieve a supine diastolic blood pressure (SuDBP) of less than 90 mm Hg. The three regimens were equally effective in lowering supine blood pressure (dilevalol daily and twice daily reduced SuDBP by 14 Hg and propranolol by 13 mm Hg). Patients with at least a 5 mm Hg reduction in SuDBP then entered a two month maintenance phase. Dilevalol, whether given once (N = 40) or twice daily (N = 55) maintained the supine systolic blood pressure more effectively (dilevalol daily--15 mm Hg, twice daily--13 mm Hg, P less than .05) than propranolol (N = 53, 11 mm Hg) and dilevalol given once daily maintained diastolic blood pressure more effectively than propranolol (17 mm Hg v 14 mm Hg, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗