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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Comparison of amlodipine and benazepril monotherapy to amlodipine plus benazepril in patients with systemic hypertension: a randomized, double-blind, placebo-controlled, parallel-group study. The Benazepril/Amlodipine Study Group.

A single-blind, run-in, randomized, double-blind, parallel-group, placebo-controlled comparison trial was conducted to assess the safety and efficacy of low-dose amlodipine 2.5 mg daily, low-dose benazepril 10 mg daily, and the combination of the two drugs at the same doses used once daily in patients (n = 401) with mild to moderate (stages I and II) systemic hypertension. Both monotherapy regimens were shown to significantly reduce both systolic and diastolic blood pressure compared with baseline placebo values, and the combination regimen was shown to be superior in lowering systolic and diastolic blood pressure when compared with either of the monotherapy regimens. The combination therapy also resulted in a greater percentage of patients having successful clinical response in mean sitting diastolic blood pressure. The amlodipine and benazepril regimen was also shown to be associated with a similar incidence of adverse experiences as the active monotherapy or placebo regimens, although the group given combination therapy appeared to have a lower incidence of edema than the group given amlodipine alone. Low-dose amlodipine (2.5 mg) plus benazepril (10 mg) provides greater blood-pressure-lowering efficacy than either monotherapy, and has an excellent safety profile.

Adult↗
PubMed1995

First-line therapy option with low-dose bisoprolol fumarate and low-dose hydrochlorothiazide in patients with stage I and stage II systemic hypertension.

This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety advantage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12.6 mm Hg) than bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieved with the low-dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Antihypertensive effects were maintained during the 24-hour dosing interval. The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety advantages over H25, as shown by less hypokalemia (< 1% with B5/H6.25 versus 6.5% with H25).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Serotonin and serotonin antagonism in cardiovascular and non-cardiovascular disease.

Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S2-serotonergic antagonist with additional alpha-adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patients receiving potassium- and magnesium-losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and "shock lung." The drug is not yet approved for clinical use in the United States.

Animals↗
PubMed1995

Controlled-release drug delivery systems in cardiovascular medicine.

Controlled-release drug delivery technology has had a significant effect on the pharmacotherapy of cardiovascular diseases. Oral and transcutaneous controlled-release systems allow relatively short-acting drugs to be administered once or twice daily with comparable therapeutic efficacy and fewer adverse reactions compared with standard formulations. They can provide decreased fluctuations in drug concentrations in plasma while possibly reducing the total amount of drug necessary for a clinical response. Techniques include the diffusion, bioerosion or degradation, and generation of osmotic pressure in orally active and transcutaneous drug delivery systems. Calcium-channel blocking agents, nitrates, beta-blocking agents, antiarrhythmic agents, clonidine, and nicotinic acid can be administered by these techniques, which have greatly influenced the application of these drugs in clinical practice.

Administration, Cutaneous↗
PubMed1995

Novel antiplatelet therapies for treatment of patients with ischemic heart disease: inhibitors of the platelet glycoprotein IIb/IIIa integrin receptor.

Blood platelets play essential roles in normal coagulation and in coronary atherosclerotic disease and its complications. Various antiplatelet therapies, including aspirin, ticlopidine, and dipyridamole, have been developed for use in patients with known coronary artery artery disease to prevent ischemic complications. More recently a more complete anti-aggregation effect has been accomplished by the use of monoclonal antibodies and specific peptide and nonpeptide compounds that bind to the platelet GP IIb/IIIa surface receptor. This receptor becomes activated by platelet stimulation and binds fibrinogen molecules between platelets in the aggregation process. These new antiplatelet drugs are now being evaluated in clinical trials in patients undergoing balloon coronary angioplasty, in whom fewer ischemic events occur when the receptor blocker is used intravenously than with standard therapy, and in patients with stable and unstable angina. Excessive bleeding is an important problem with these agents, and efforts must be made to eliminate this side effect.

Abciximab↗
PubMed1995

Nitric oxide donors in the treatment of cardiovascular and pulmonary diseases.

NO has been shown to be a biologic substance important to normal physiologic functioning. It appears to be an endogenous vasodilator and is involved in hemostasis and inflammation. Endothelial cell dysfunction often leads to diminished NO production; this reduction in NO concentrations may be an etiologic factor in systemic hypertension, myocardial and splanchnic ischemia, atherosclerosis, CHF, and pulmonary vascular disease. A new class of drugs, NO donors, have potential utility in the treatment of coronary and pulmonary arterial diseases. Their major advantage over nitrates and nitroprusside is a lack of pharmacologic tolerance. Clinical trials with drugs of this class are now in progress.

Cardiovascular Diseases↗
PubMed1995

Endothelin and endothelin antagonism: roles in cardiovascular health and disease.

Endothelin is the most potent mammalian vasoconstrictor yet discovered. Its three isoforms play leading roles in regulating vascular tone and causing mitogenesis. The isoforms bind to two major receptor subtypes (ETA and ETB), which mediate a wide variety of physiologic actions in several organ systems. Endothelin may also be a disease marker or an etiologic factor in ischemic heart disease, atherosclerosis, congestive heart failure, renal failure, myocardial and vascular wall hypertrophy, systemic hypertension, pulmonary hypertension, and subarachnoid hemorrhage. Specific and nonspecific receptor antagonists and ECE inhibitors that have been developed interfere with endothelin's function. Many available cardiovascular therapeutic agents, such as angiotensin-converting-enzyme inhibitors, calcium-entry blocking drugs, and nitroglycerin, also may interfere with endothelin release or may modify its activity. The endothelin antagonists have great potential as agents for use in the treatment of a wide spectrum of disease entities and as biologic probes for understanding the actions of endothelin in human beings.

Amino Acid Sequence↗
PubMed1995

Addition of zatebradine, a direct sinus node inhibitor, provides no greater exercise tolerance benefit in patients with angina taking extended-release nifedipine: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The Zatebradine Study Group.

OBJECTIVES: We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine. BACKGROUND: Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs. METHODS: In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks. RESULTS: Zatebradine reduced rest heart rate both at 4 weeks ([mean +/- SEM] 12.9 +/- 1.23 vs. 2.3 +/- 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 +/- 1.2 vs. 3.4 +/- 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions. CONCLUSIONS: Zatebradine seems to provide no additional antianginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.

Adult↗
PubMed1995

Vesnarinone: a new inotropic agent for treating congestive heart failure.

Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. There is increased mortality with vesnarinone at the 120 mg daily dose, however, suggesting a narrow therapeutic window for the drug. Its predominant toxic side effect is a 2% incidence of reversible neutropenia.

Cardiotonic Agents↗
PubMed1995

Drug utilization in the old old and how it relates to self-perceived health and all-cause mortality: results from the Bronx Aging Study.

OBJECTIVE: To characterize medication use in a "well" very old population and relate the quantity and type of medication use to 10-year mortality. DESIGN AND SUBJECTS: A longitudinal, 10-year, follow-up study involving 488 healthy, community-dwelling volunteers aged 75 to 85 years. The subjects underwent a detailed baseline evaluation and annual assessments that included comprehensive physical exams, laboratory and diagnostic tests, and related interviews. Prescription and nonprescription drug use was determined by self report, confirmation through hospital records, and reports by subjects and significant others. RESULTS: At study baseline, the mean number of prescription and nonprescription medications used was 2.3 and 1.5, respectively. Female subjects (n = 315), those older than 80 years, or those who reported themselves to be in fair or poor health on initial health self-report were found to show significantly increased use of prescription medications. The most commonly used classes of medications were cardiovascular drugs and analgesics. Subjects who were consuming a greater number of prescription and nonprescription medications did not have higher mortality rates. After correcting for differences in cardiovascular health status between users and nonusers, only digoxin approached significance as an independent predictor of death (P < .08). CONCLUSION: This study confirmed that medication use in an ambulatory, old old population is not excessive. The oldest subjects in the cohort consumed more medications than did the younger subjects. Women used more prescription drugs than men. Increased medication use was associated with worse ratings on health self report. Medication use alone, however, was not a predictor of 10-year mortality in this population. Questions are raised about the inappropriate prescription of digoxin in older subjects.

Aged↗
PubMed1995

beta-blockers. Drug interactions of clinical significance.

The clinician prescribing beta-blockers for his or her patients is faced with an often difficult situation. There are many beta-blockers, each with its own pharmacological profile. Patients are often taking multiple medications, thus increasing the risk of both anticipated and unexpected drug interactions. Reports of drug interactions are frequently anecdotal. The prescriber may not be aware of the patient's other medications or lifestyle habits. Pharmacokinetic and pharmacodynamic drug interactions involving beta-blockers are documented in the literature, but these studies often examine small numbers of patients. For these reasons, it is difficult for the practitioner to distill guidelines for the administration of beta-blockers in conjunction with other medication. In general, beta-blockers are well tolerated, and symptomatic drug interactions are relatively infrequent. It is incumbent upon the clinical practitioner to have knowledge of his or her patient's drug profile and to be aware of the various drug interactions as well as each patient's unique pathophysiological profile when prescribing any medication, including beta-blockers. beta-Blockers may interact with a large number of commonly prescribed drugs, including antihypertensive and antianginal drugs, inotropic agents, anti-arrhythmics, NSAIDs, psychotropic drugs, anti-ulcer medications, anaesthetics, HMG-CoA reductase inhibitors, warfarin, oral hypoglycaemics and rifampicin (rifampin).

Adrenergic beta-Antagonists↗
PubMed1994

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.

BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.

Bisoprolol↗
PubMed1994

Amlodipine versus atenolol in essential hypertension.

The efficacy and safety of amlodipine (2.5-10 mg) once daily was compared with atenolol (50-100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, double-blind, parallel, placebo-controlled study. A total of 125 patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks of double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The placebo group had small mean changes in supine and standing blood pressure compared with baseline. The mean blood pressure changes from baseline 24 hours postdose in the amlodipine group (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine blood pressure and -11.5/-9.8 mm Hg for standing blood pressure (p < 0.001 compared with placebo), and for the atenolol group (mean daily dose 83.7 mg) the changes were -11.3/-11.7 mm Hg for supine blood pressure and -13.3/-12.3 mm Hg for standing blood pressure (p < 0.001 compared with placebo). There were no statistically significant blood pressure differences between active treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1, 64.9, and 11.1%, respectively. The blood pressure values taken over the 24-hour period at final visit revealed that amlodipine and atenolol maintained the supine blood pressure < or = 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Both amlodipine and atenolol were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Topical ophthalmic beta-adrenergic blockade for the treatment of glaucoma and ocular hypertension.

Since the late 1970s, topical beta-adrenergic blockers have been the drugs of choice in treating ocular hypertension and associated glaucoma. The currently available drugs are timolol, betaxolol, levobunolol, metipranolol, and carteolol. All reduce intraocular pressure by decreasing the production of aqueous humor. Although these drugs are applied locally in the eye, they may enter the general circulation and reach concentrations high enough to cause systemic effects, including alterations in heart rate and rhythm, bronchoconstriction, dyslipidemia, and central nervous system abnormalities. Interactions with other drugs may also occur. Ocular beta- blockers differ in beta 1-selectivity (betaxolol is beta 1-selective, whereas the other drugs are nonselective) and in intrinsic sympathomimetic activity (ISA) or partial agonist properties (only carteolol possesses ISA). These differences give betaxolol and carteolol potential advantages in minimizing certain side effects. The advantage of betaxolol vis-à-vis systemic side effects is more clearly established than that of carteolol. Further systematic study is needed to determine what advantages, if any, are conferred by the presence of ISA.

Administration, Topical↗
PubMed1994

Ischemic hepatitis in a patient with congestive cardiomyopathy: an innovative approach to therapy using intravenous dobutamine.

Patients who sustain a transient period of hypotension or low cardiac output can develop massive elevations of the serum transaminases without serum markers of acute hepatitis, a recent myocardial infarction or exposure to toxins and chemicals. This condition is often termed "ischemic hepatitis" (IH), with its pathological correlate being centrilobular necrosis. Recognition of IH can help in the appropriate management of these patients, and avoid unnecessary diagnostic testing. The authors describe a patient with congestive cardiomyopathy in whom IH developed as part of a complicated hospital course. The condition appeared to reverse with the administration of dobutamine, suggesting inotropic therapy as an appropriate treatment modality.

Adult↗
PubMed1994

Renin inhibition: a new approach to cardiovascular therapy.

The renin-angiotensin system (RAS) functions as a primary regulator in the short-term and long-term control of blood pressure. Pharmacologic inhibition of the RAS with angiotensin-converting enzyme (ACE) inhibition is effective for treating systemic hypertension and congestive heart failure. As a more specific therapy, the development of renin inhibitors has evolved through various approaches: specific renin antibodies, peptides developed from prosegments of renin precursor, oligopeptides related to pepstatin a universal inhibitor of aspartyl proteinase enzyme, and analogs of angiotensinogen (the renin substrate). Angiotensinogen analogs are promising as therapeutic agents because of high potency, metabolic stability, and good oral bioavailability. Ongoing research is directed towards the application of renin inhibition, the treatment of various cardiovascular disorders, and as a biological probe for understanding the role of the RAS in control of blood pressure and blood volume.

Amides↗
PubMed1994

Atrial natriuretic peptide and its potential role in pharmacotherapy.

Atrial natriuretic peptide (ANP) is a 28 amino-acid polypeptide secreted into the blood by atrial myocytes after atrial pressure and distension. Although its role in humans is not clear, it can produce a variety of physiologic effects including vasodilatation, natriuresis, and suppression of the renin-angiotensin-aldosterone axis. These actions are potentially useful in a variety of pathologic states such as hypertension and congestive heart failure, and diverse methods to augment the effects of ANP in these states have been devised. The results are exciting and, despite some problems, may lead to the pharmacologic use of enhancement of ANP actions in several clinical disorders.

Atrial Natriuretic Factor↗