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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 91 records · Page 5Linked to original sources
PubMed1994

Calcium-channel entry blocker therapy for hypertensive patients with concomitant renal impairment: a focus on isradipine.

In the treatment of hypertension in renally impaired patients, normalization of blood pressure alone may not be sufficient to prevent significant morbidity to the kidneys. Treatment must reduce pressure in the renal vasculature, otherwise glomerular filtration rate and renal plasma flow will continue to deteriorate. Isradipine a dihydropyridine calcium-channel blocker, has been investigated as a suitable treatment in this setting. Isradipine maintains glomerular filtration rate, preserves or enhances renal plasma flow, decreases renal vascular resistance, maintains or reduces filtration fraction, and exerts a sustained natriuretic effect, all of which may enable isradipine to slow the rate of progression of renal deterioration. In addition, isradipine may decrease proteinuria and may decrease glomerular capillary pressure by dilating both the efferent and afferent arterioles. Unlike older calcium-channel blockers, isradipine exhibits minimal cardiodepressant activity and is not associated with any negative inotropic effects. It is metabolized in the liver and dosage adjustments may not be necessary when administered to patients with renal insufficiency. Isradipine has a favorable renal effect profile and also has several properties that meet the requirements of other patient populations where an extra measure of antihypertensive safety is required, such as diabetics, dialysis patients, and transplant recipients. Side effects with isradipine are usually mild and transient, occurring in a dose-dependent manner.

Calcium Channel Blockers↗
PubMed1994

Angiotensin II receptor antagonists: a new approach to blockade of the renin-angiotensin system.

A-II exerts its activity on various target tissues by binding to its receptors. The discovery of local RASs and A-II receptors within various tissues has generated interest in the clinical usefulness of RAS inhibition by directly blocking the action of A-II at the receptor level. Different A-II receptor subtypes have been identified and subsequently termed AT1 and AT2. AT1-receptor subtypes are the predominant receptor subtypes existing in most organs and, by coupling to a transmembrane G protein, seem to be the main subtypes participating in the vasoactive responses of A-II. Saralasin, a peptide with specific A-II receptor-antagonistic activity, had limited practical long-term usefulness as a result of its short half-life, significant agonistic properties, and lack of oral bioavailability. The discovery of simple benzyl-substituted imidazoles, which possess weak but highly selective A-II receptor antagonistic properties, led to the development of losartan (DuP 753). Losartan is a potent, orally active, specific, competitive nonpeptide A-II receptor antagonist that appears to be an effective antihypertensive agent both in animal studies and in preliminary clinical trials. The therapeutic usefulness of losartan, however, is not limited to its antihypertensive effects. The potential benefits of A-II receptor antagonists include roles in postmyocardial infarction therapy, slowing A-II-induced cardiac hypertrophy, 154, 155 slowing the progression of heart failure, preventing postangioplasty restenosis, and in slowing the progression of renal disease. Furthermore, losartan, a selective A-II type 1 (AT1) receptor antagonist, has also been a valuable pharmacologic probe for studying the mechanism of A-II stimulation of its receptors. A-II receptor antagonism appears to be as effective as ACE inhibition in the treatment of hypertension and other pathologic processes that involve the RAS and may offer an alternative to those patients who cannot tolerate ACE inhibitors because of their side effects.

Angiotensin Receptor Antagonists↗
PubMed1994

Intranasal delivery of cardiovascular agents: an innovative approach to cardiovascular pharmacotherapy.

The intranasal administration of drugs has long been used for the topical treatment of various nasal disorders. Many features of the intranasal mucosa also make it useful for delivery of systemically active agents. It has been shown that intranasal drug administration can provide plasma drug levels similar to those observed with comparable doses of parenteral drugs. The feasibility of intranasal administration of propranolol, nifedipine, and nitroglycerin has been investigated in several small clinical studies. Intranasal propranolol has been shown to improve exercise tolerance in patients with angina pectoris. Intranasal nifedipine has been used to treat patients with perioperative hypertension and hypertensive crisis. Intranasal administration of nitroglycerin was shown to blunt the hypertensive response to endotracheal intubation. These studies and others suggest that intranasal delivery of cardiovascular drug treatment could be used in those clinical situations where a rapid or intermittent drug effect is desired and can potentially serve as an alternative to parenteral drug administration.

Absorption↗
PubMed1994

Serum vitamin B12 levels and incidence of dementia in a healthy elderly population: a report from the Bronx Longitudinal Aging Study.

OBJECTIVE: To determine whether low serum B12 levels are associated with an increased incidence of dementing illness. DESIGN: Longitudinal cohort study, 5-year follow-up. PARTICIPANTS: Volunteer cohort of 410 nondemented ambulatory subjects aged 75 to 85 years. MEASUREMENTS: Annual serum B12 determinations and neuropsychological assessments including the Blessed Test of Information, Memory and Concentration (BIMC) and the Fuld Object Memory Evaluation (FOME). If subject met criteria for a major cognitive change (as defined by an increase of 4 or more points on the BIMC), a work-up that included CT, EEG, and neurologic assessment was performed. Clinical diagnoses were made according to established criteria. RESULTS: Mean serum B12 level of entire sample was 558 pg/mL. Twenty-two subjects had low B12 levels defined as values < 150 pg/mL. Three of these 22 subjects (13.6%) became demented, compared with 57 of 388 subjects (14.7%) with higher levels. The incidence of Alzheimer disease among the low B12 group was 4.5% compared with 7.5% in the higher B12 group. The mean B12 level at time of diagnosis in subjects who did develop Alzheimer disease was 551 pg/mL. There was no evidence of hematologic disorder among the 22 subjects with low B12. Of the 3 low B12 subjects who did become demented, none responded to monthly B12 injections. CONCLUSION: A low B12 level may not be a risk factor for dementia in general or Alzheimer disease in particular.

Aged↗
PubMed1993

Improvement in exercise tolerance and immediate beta-adrenergic blockade with intranasal propranolol in patients with angina pectoris.

A new intranasal spray formulation of propranolol was developed to provide beta-adrenergic blocking medication on an immediate basis to patients with angina pectoris. The effects of this spray or placebo were assessed in 16 patients with effort-induced angina in a blinded, randomized, cross-over design study that compared placebo with intranasal propranolol spray (5 mg/puff) 15 minutes before exercise on a treadmill (Bruce protocol). One week later, each patient, acting as his/her own control, received the alternative treatment and repeated exercise. Mean plasma propranolol level with active therapy was 20 ng/ml. Patients with active spray demonstrated a significant increase in total exercise time than patients taking placebo (530 +/- 197 vs 460 +/- 177 seconds, p = 0.05), an increase in the time to 1 mm ST-segment depression on the electrocardiogram (384 +/- 202 vs 327 +/- 144 seconds, p < 0.05), and an increase in time to onset of angina (452 +/- 149 vs 363 +/- 175 seconds, p = 0.0005). There was a blunting of maximal exercise heart rate with active therapy compared with placebo (120 +/- 13 vs 133 +/- 17 beats/min, p < 0.01), blunting of maximal exercise systolic blood pressure (185 +/- 22 vs 194 +/- 21 mm Hg, p < 0.05), and blunting of peak double product (p < 0.0005), with more modest effects on resting heart rate. Propranolol spray is an effective approach for providing immediate beta blockade and improving exercise tolerance in patients with angina pectoris.

Administration, Intranasal↗
PubMed1993

Angiotensin II receptor blockade: an innovative approach to cardiovascular pharmacotherapy.

Through the multiple actions of angiotensin II (AII), the renin-angiotensin system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by binding to specific membrane-bound receptors, which are coupled to one of several signal transduction pathways. These AII receptors exhibit heterogeneity, represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major cardiovascular action of the RAS. This receptor has been cloned from multiple species, disclosing features consistent with a transmembrane, G-protein-linked receptor. Further AII receptor heterogeneity is evident by the cloning of isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor is the most direct site to inhibit the actions of the RAS. Many AII receptor antagonists, including peptide analogs of AII and antibodies directed against AII, possess unfavorable properties that have limited their clinical utility. The discovery and further development of imidazole compounds with AII antagonist properties and favorable characteristics, however, has promise for clinical utility. The leader in this field is a selective AT1 receptor antagonist losartan (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an effective antagonist of many AII-induced actions and an effective antihypertensive agent in many animal models of hypertension (HTN). Losartan also demonstrated secondary benefits in preventing stroke, treating congestive heart failure (CHF), and delaying the progression of renal disease in animal models. Clinical studies confirm the AII antagonist action of losartan and suggest that losartan will be effective in the treatment of essential HTN. AII antagonism is likely to provide useful treatment in essential HTN and CHF, conditions in which the RAS is known to play a major role. The utility of AII antagonism may extend beyond that of HTN and CHF, as suggested by the potential usefulness of angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of many other diseases. The key advantage AII antagonists provide over ACE inhibitors is that they may avoid unwanted side effects, related to bradykinin potentiation with the latter drugs. The AII antagonists will help determine the role of the RAS in physiologic regulation and in the pathophysiology of various disease states.

Angiotensin II↗
PubMed1993

A new extended-release formulation of diltiazem HCl for the treatment of mild-to-moderate hypertension.

Calcium-channel blockers are a safe and effective treatment modality and have been used extensively in the treatment of angina and hypertension. Dilacor XR capsules, a new extended-release formulation of diltiazem, has been developed for the treatment of hypertension. Dilacor XR (Rhône-Poulenc Rorer Pharmaceuticals Inc., Collegeville, PA) uses a novel drug delivery system, the Geomatrix (JAGO Research AG, Zollikon, Switzerland) controlled-release system, to deliver diltiazem at a constant rate for 24 hours. The rate of absorption is also slower. As doses of Dilacor XR were increased from 120 mg to 540 mg/day, there were disproportionate increases observed in area under the curve, maximum peak plasma concentration, minimum peak plasma concentration, and average peak plasma concentration. The efficacy data from two clinical trials have confirmed the established efficacy of diltiazem and the 24-hour efficacy of Dilacor XR in the control of mild-to-moderate hypertension. The incidence of adverse effects with Dilacor XR in doses as high as 540 mg/day was generally comparable to that of placebo. This new extended-release formulation of diltiazem should significantly facilitate blood pressure control because of better patient compliance with a once daily regimen.

Blood Pressure↗
PubMed1993

Combination drug therapy with calcium-channel blockers in the treatment of systemic hypertension.

Calcium-channel blockers have been shown to be both safe and effective for treatment of patients with systemic hypertension. These drugs reduce peripheral vascular resistance predominantly by the inhibition of transmembrane calcium ion fluxes in vascular smooth muscle, and by this mechanism can reduce elevated blood pressure. To maximize blood pressure lowering efficacy in patients, calcium-channel blockers have also been used in combination with other antihypertensive treatments that have included diuretics, beta-adrenergic blockers, and angiotensin-converting enzyme inhibitors.

Adrenergic beta-Antagonists↗
PubMed1993

Internal medicine housestaff and attending physician perceptions of the impact of the New York State Section 405 regulations on working conditions and supervision of residents in two training programs.

OBJECTIVES: To assess the attitudes of internal medicine housestaff and their attending physicians regarding the impact of the reduction in on-call working hours and increased supervision mandated in New York by a revision of the State Health Code (Section 405). DESIGN: Survey of senior medical housestaff and attendings two years after the adoption of the mandated changes. SETTING: Two independent medicine housestaff training programs of the Albert Einstein College of Medicine in the Bronx, New York. PARTICIPANTS: Fifty-three percent of third- and fourth-year residents (n = 79) and 60% of voluntary and full-time attendings (n = 266) responded. MEASUREMENTS: A factor analysis of 13 variables that appeared on both versions of the survey identified two interpretable factors. A multivariate analysis of variance compared responses to each factor by group and by campus, and Bonferroni post-hoc comparisons analyzed the items within factors. Chi-square analyses compared responses of residents and attendings to the open-ended questions. RESULTS: Significant differences between the housestaff and attendings groups were found for all fixed-response items (minimum p < 0.05 for all analyses), but both groups agreed that the regulations had a positive impact on resident attitudes regarding the demands on their time. Both groups were also uncertain whether the new regulations had a beneficial effect on the choice of internal medicine as a career, the quality of resident supervision, and residents' intellectual interest in challenging medical problems. Whereas residents agreed that the regulations diminished their fatigue, had no impact on their ability to observe the full impact of interventions on patients, and resulted in better patient care, attendings were uncertain or disagreed. While attendings agreed that the regulations had caused a shift-work mentality among residents, housestaff were uncertain. CONCLUSIONS: Housestaff had more positive attitudes about the impact of the mandated changes in working conditions for residents than did attending physicians in the same institutions. The major benefits seen by residents were less fatigue and more spare time. There was no consensus about whether these changes had a positive impact on internal medicine practice and clinical supervision. There was some concern that a shift-work mentality is developing among residents and that continuity of patient care has suffered. Thus, despite some substantial benefits, Section 405 may not be achieving its goals of improving resident supervision and the quality of patient care by houseofficers.

Attitude of Health Personnel↗
PubMed1993

Treatment of myocardial ischemia and myocardial infarction in the elderly.

The diagnosis of coronary artery disease in the elderly is problematic because older patients often present atypical symptoms or are asymptomatic. Once coronary disease is diagnosed, the proper course of treatment is not always clear, since few studies have focused on patients older than 65 years. Moreover, older patients often have medical conditions that may aggravate coexisting cardiovascular problems or interfere with conventional pharmacotherapy. For these reasons many physicians who treat cardiovascular problems aggressively in younger patients are reluctant to do so in older individuals. There is considerable evidence, however, that older patients could benefit as much or more from aggressive therapy because of their greater risk of mortality from myocardial ischemia and infarction.

Age Factors↗
PubMed1993

Acute hyperglycaemic effect of anaesthetic induction with thiopentone.

The acute effects of thiopentone on plasma glucose concentration and regulation in humans have not been well described. We therefore examined the effect of a single dose (6 mg/kg) of thiopentone on plasma glucose, insulin, glucagon, adrenaline and noradrenaline in 16 healthy women undergoing elective abdominal surgery. To assess involvement of the neuroendocrine system in the response to thiopentone, half of the patients received labetalol prior to induction of anaesthesia. Thiopentone injection resulted in a 50% increase in plasma glucose levels (P < 0.001) in both labetalol-treated and non-treated patients 90 s following its administration. This was associated neither with significant increases in plasma glucagon, adrenaline and noradrenaline nor with a decline in plasma insulin. We conclude that acute hyperglycaemia following thiopentone is most likely the consequence of a non-adrenergically-mediated increase in hepatic glucose release.

Acute Disease↗
PubMed1992

Beta-adrenergic blockers as cardioprotective agents.

The evidence supporting and describing cardioprotective effects of beta-adrenergic blocker treatment is surveyed. Details of the many studies that individually and collectively document the ability of long-term and acute beta-blocker therapy to reduce overall mortality, sudden cardiovascular death, and nonfatal reinfarction in patients surviving or experiencing a myocardial infarction are described. A discussion of the mechanisms by which beta blockers probably and theoretically achieve these benefits includes the suggestion that they may reduce plaque rupture, thus indirectly inhibiting thrombosis. It is also suggested that, in the future, further cardioprotective benefits may accrue to the use of beta blockers in conjunction with thrombolysis and of beta blockers with a duration of action sustained throughout a full 24 hours.

Adrenergic beta-Antagonists↗
PubMed1992

Comparison of sustained-release formulations of nicardipine and verapamil for mild to moderate systemic hypertension.

In this double-blind, parallel, multicenter study, sustained-release (SR) preparations of 2 calcium antagonists, nicardipine and verapamil, were compared for the treatment of mild to moderate systemic hypertension. Two hundred eighteen patients with supine diastolic blood pressures (BP) 95 to 114 mm Hg were randomly assigned to receive nicardipine-SR 45 mg twice daily (n = 73), nicardipine-SR 60 mg twice daily (n = 73) or verapamil-SR 240 mg once daily in the morning (n = 72). All 3 regimens significantly reduced supine and sitting systolic and diastolic BPs compared with baseline values (p < 0.005). The efficacy of drugs became apparent after 2 weeks of therapy, and was sustained throughout the 12-week study. Reductions in sitting diastolic BP and supine and sitting systolic BPs were statistically greater with nicardipine-SR 60 mg twice daily compared with verapamil, and nicardipine-SR 45 mg twice daily was equivalent to verapamil. Asthenia and constipation occurred more frequently in patients treated with verapamil (9.7 and 11.1%, respectively, compared with 6.8 and 4.1% in either nicardipine group). Adverse events reported more frequently with nicardipine were headache (17.8% with nicardipine-SR 60 mg and 15.1% with nicardipine-SR 45 mg vs 13.9% with verapamil) and edema (15.1% in the nicardipine-SR 60 mg group, 8.2% with nicardipine-SR 45 mg vs 4.2% with verapamil). Verapamil, but not nicardipine, produced significant reductions in heart rate. SR preparations of calcium antagonists offer options for effective monotherapy of systemic hypertension. Side-effect profiles differ and may affect choice of therapy.

Delayed-Action Preparations↗
PubMed1992

Tolerance, rebound, and time-zero effect of nitrate therapy.

Both nitroglycerin and long-acting nitrates have proved effective in treating acute anginal pain. In recent years, however, development of tolerance with the continuous use of these agents has been documented. A pilot study demonstrated attenuation of the therapeutic effect of high-dose, continuous transdermal nitroglycerin therapy, despite adequate plasma nitroglycerin levels. In a subsequent, larger Transdermal Nitroglycerin Cooperative Study, evidence of tolerance was detected within 24 hours of initiation of continuous nitroglycerin patch therapy at several different dose levels. Sustained pharmacologic activity has been achieved with the intermittent use of transdermal nitroglycerin, usually for 12 hours followed by a 12-hour drug-free period. When the patch is discontinued, however, some patients experience exacerbation, or rebound, of anginal symptoms and a worsening of exercise tolerance at the end of the drug-free period. Additional clinical research is therefore needed to determine the optimal intermittent dosing strategy.

Administration, Cutaneous↗
PubMed1992

Comparative efficacy and concomitant use of bepridil and beta blockers in the management of angina pectoris.

The efficacy and safety of bepridil hydrochloride (HCl) and propranolol HCl monotherapy were investigated in a double-blind, parallel-group crossover study in 75 patients with chronic stable angina pectoris. For the first double-blind segment, both drugs reduced the frequency of weekly anginal attacks and nitroglycerin consumption. On exercise testing, bepridil was significantly more effective in terms of increasing time to angina and total work. Heart rate and ST-segment depression decreased to a greater degree with propranolol than bepridil. Bepridil produced a greater increase in QT interval than propranolol; corrected QT (QTc) interval was increased by bepridil and slightly decreased by propranolol. The incidence of adverse effects was roughly comparable for the two active drugs and higher than that for placebo during washout periods. It was concluded that bepridil, at a mean maintenance dosage of 324 mg/day, was at least as effective as propranolol in improving exercise tolerance--specifically time to angina and total work--and that tolerability of the 2 drugs was comparable. In another study, the efficacy and safety of bepridil combined with propranolol were compared with that of placebo plus propranolol in 56 patients who had not been well controlled on propranolol alone. The addition of bepridil significantly reduced the frequency of anginal attacks and weekly nitroglycerin consumption compared with baseline. The combination of propranolol and bepridil also produced significant improvements in total exercise time, time to angina, and total work compared with baseline. The QTc interval increased significantly from baseline in the bepridil combination group and decreased significantly in the propranolol plus placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗