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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 109 records · Page 6Linked to original sources
PubMed1992

Comparative pharmacokinetic and clinical profiles of angiotensin-converting enzyme inhibitors and calcium antagonists in systemic hypertension.

Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists are important classes of antihypertensive agents. Within their respective classes, ACE inhibitors and calcium antagonists share common pharmacokinetic properties, but in contrast to ACE inhibitors, some calcium antagonists may cause a significant increase in plasma digoxin concentrations. Clinically, both classes of agents have been shown to be safe and effective in large-scale, long-term clinical trials. ACE inhibitors appear to be very well tolerated and may be associated with fewer adverse effects than some calcium antagonists. ACE inhibitors appear to blunt diuretic-induced hypokalemia, hypercholesterolemia, hyperuricemia, and hyperglycemia. Both classes of agents can be used safely in patients with renal disease, diabetes mellitus, peripheral vascular disease, and chronic obstructive pulmonary disease. They may also be used in the elderly. While ACE inhibitors are particularly useful in hypertension accompanied by congestive heart failure, calcium antagonists can be very useful when angina pectoris is present in the hypertensive patient.

Aging↗
PubMed1992

Antihypertensive and metabolic effects of concomitant administration of terazosin and methyclothiazide for the treatment of essential hypertension.

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

Adrenergic alpha-Antagonists↗
PubMed1992

Sustained-release verapamil formulations for treating hypertension.

Verapamil, the first calcium-channel blocker to be introduced for clinical use, is a major drug used for the treatment of systemic hypertension. During the past 10 years, the use of verapamil for hypertension has produced a considerable clinical database to support the efficacy and safety of the agent in many patients. Because of its short half-life, verapamil was originally administered 3 to 4 times daily. During the past decade, a sustained-release formulation of verapamil has been marketed in the US. This product allows for once-daily dosing up to 240 mg/d; however, when higher doses are needed, this sustained-release formulation should be administered twice daily. In addition, the medicine should be taken with food to avoid the high peak blood levels of verapamil, which appears to be related to the delivery system. A new pellet-filled capsule formulation of verapamil (Verelan, Lederle, Wayne, NJ and Wyeth-Ayerst, Philadelphia, PA) is available and provides controlled absorption, 24-hour blood pressure control, improved peak-to-trough plasma levels, and once-daily dosing regardless of dosage size. Prolonged-release verapamil can be taken without food.

Administration, Oral↗
PubMed1992

Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study.

This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.

Aged↗
PubMed1992

A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension.

The efficacy and safety of amlodipine (2.5 mg, 5 mg, or 10 mg) once daily was compared with atenolol (50 mg to 100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, double-blind, parallel, placebo-controlled study. One hundred and twenty-five patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks' double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The mean changes from baseline in blood pressure 24 h postdose for amlodipine (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine and -11.5/-9.8 mm Hg for standing blood pressure (P < .001). For atenolol (mean daily dose 83.7 mg) the changes were -11.3/-11.7 mm Hg for supine and -13.3/-12.3 mm Hg for standing blood pressure (P < .001). There were no statistically significant differences between treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1%, 64.9%, and 11.1%, respectively. Determinations taken over the 24-h period at the final visit revealed that amlodipine and atenolol maintained the group mean supine blood pressure at or below 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well-tolerated. Only one patient was withdrawn because of the development of peripheral edema, arthralgia, and fatigue after treatment with amlodipine. This study demonstrates that once-daily administration of amlodipine or atenolol to mild-to-moderate hypertensive patients was well-tolerated and provided adequate blood pressure control throughout the 24-h dosing interval.

Adolescent↗
PubMed1992

Hypertension: cardiovascular implications in a cohort of old old.

OBJECTIVE: To examine the prevalence and cardiovascular implications of hypertension in advanced age. DESIGN: Prospective non-interventional study of a fixed cohort of very elderly subjects. PARTICIPANTS AND SETTING: The subjects were 488 community-dwelling volunteers. Mean age at entry was 79 years (range 75-85). All subjects were ambulatory, non-demented, and free of terminal illness at baseline. Participants were evaluated at the gerontology department of an urban medical school. MAIN OUTCOME MEASURES: Cardiovascular morbid and mortal events that were followed included fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, and death. Prevalence of unrecognized myocardial infarction defined by electrocardiographic changes was also assessed. RESULTS: When hypertension was defined by history, current use of medications, or measured elevations in blood pressure, 78% of the subjects could be considered hypertensive. Univariate analysis showed an increased incidence of strokes in subjects with measured hypertension (P = 0.04). Subjects with elevated blood pressure (untreated) were more likely to develop clinically unrecognized myocardial infarction (P = 0.017). Multivariate survival analysis showed hypertension to be a modest predictor of overall cardiovascular disease (P = 0.067) but not of all-cause mortality. Left ventricular hypertrophy was a predictor of cardiovascular disease (P = 0.013) and all-cause mortality (P = 0.008). Age remained a significant risk factor for these endpoints, even in the very old. Isolated systolic hypertension was analyzed separately and in univariate analysis was a risk factor for stroke but not other cardiovascular morbidity. CONCLUSIONS: Hypertension at advanced age remains a modestly important risk factor in the development of cardiovascular disease.

Age Factors↗
PubMed1992

Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. The Bronx Aging Study.

The Bronx Aging Study is a 10-year prospective investigation of very elderly volunteers (mean age at study entry, 79 years; range, 75-85 years) designed to assess risk factors for dementia and coronary and cerebrovascular (stroke) diseases. Entry criteria included the absence of terminal illness and dementia. All subjects (n = 350) included in this report had at least two lipid and lipoprotein determinations. Overall, more than one third of subjects showed at least a 10% change in lipid and lipoprotein levels between the initial and final measurements. Moreover, mean levels for women were consistently different than those for men, and because of this finding subjects were classified into potential-risk categories based on the changes observed by using their sex-specific lipid and lipoprotein distributions. The incidences of cardiovascular disease, dementia, and death were compared between risk groups. Proportional-hazards analysis showed that in men a consistently low high density lipoprotein cholesterol level (less than or equal to 30 mg/dl) was independently associated with the development of myocardial infarction (p = 0.006), cardiovascular disease (p = 0.002), or death (p = 0.002). For women, however, a consistently elevated low density lipoprotein cholesterol level (greater than or equal to 171 mg/dl) was associated with myocardial infarction (p = 0.032). Thus, low high density lipoprotein cholesterol remains a powerful predictor of coronary heart disease risk for men even into old age, while elevated low density lipoprotein cholesterol continues to play a role in the development of myocardial infarction in women. The findings suggest that an unfavorable lipoprotein profile increases the risk of cardiovascular morbidity and mortality even at advanced ages for both men and women.

Aged↗
PubMed1991

Comparative cost-effectiveness analysis of quinidine, procainamide and mexiletine.

Quinidine and procainamide have the potential for major organ toxicity, whereas mexiletine has been reported to have little risk of organ toxicity, serious proarrhythmia or congestive heart failure, but a relatively high incidence of nuisance side effects. In light of the potential adverse effects of all antiarrhythmic agents as highlighted by the Cardiac Arrhythmia Suppression Trial, the relative cost-effectiveness of these 3 agents was assessed. Based on a review of greater than 1,000 published reports, studies included in the analysis examined greater than or equal to 1 of these agents in adults, with adequate efficacy or safety data, or both. The majority of studies assessed patients with symptomatic or malignant arrhythmias, or both. Data were analyzed using a decision analysis/cost-effectiveness model. Probabilities were averaged using techniques of meta-analysis. Costs were obtained from a university medical center cost-accounting system and from expected follow-up visits to university clinics. Thirty-seven separate side effects were included in the analysis. In terms of overall cost, 12 months of mexiletine would engender $875, quinidine $1,239 and procainamide $1,911 of expenses. Mexiletine dominates the older agents in terms of cost per successful drug response, a result that holds over a wide range of efficacy and safety data. Analyses demonstrated no increase in all-cause mortality for quinidine and mexiletine over placebo, but a trend toward higher mortality with procainamide. The results suggest that mexiletine is a cost-saving alternative therapy for ventricular arrhythmias when adverse reactions are considered in addition to pharmaceutical costs and treatment efficacy.

Ambulatory Care↗
PubMed1991

Usefulness of oral nisoldipine for stable angina pectoris. The Nisoldipine Multicenter Angina Study Group.

The duration and extent of antianginal effects of nisoldipine, a dihydropyridine calcium antagonist, were assessed in 178 patients with chronic stable angina pectoris. Using a placebo run-in, placebo-controlled, randomized, parallel study design, patients received placebo twice daily for 2 to 3 weeks and were then randomized to receive either placebo (n = 42), nisoldipine 10 mg once daily (n = 44), nisoldipine 10 mg twice daily (n = 47) or nisoldipine 20 mg once daily (n = 45) for 5 weeks. Frequency of angina and nitroglycerin consumption were assessed by weekly patient diaries. Exercise tolerance time was assessed at baseline and at weeks 1, 3 and 5 in the double-blind phase. Peak effects after 5 weeks of double-blind medication showed significant or nearly significant improvements with nisoldipine over placebo in time-to-termination of exercise, time to onset of angina, and time to onset of 1 mm ST-segment depression. There were no significant improvements in trough effects with nisoldipine. Also, placebo was not significantly different from nisoldipine in either the number of anginal attacks or nitroglycerin consumed. Although significantly more drug-related, adverse effects were observed with the nisoldipine regimen, 20 mg once daily, compared with placebo, nisoldipine appears to be an effective and well-tolerated antianginal drug. However, its duration of antianginal action, as measured by exercise stress testing, is relatively short. The drug needs to be examined using shorter dosing intervals and higher daily doses, or in a longer-acting sustained-release formulation.

Administration, Oral↗
PubMed1991

Epidemiology, pathophysiology, and management of isolated systolic hypertension in the elderly.

Isolated systolic hypertension (ISH) is a common disorder in the elderly, carrying with it a high risk of cardiovascular morbidity and mortality. Environmental and age-related factors believed to contribute to ISH include obesity, declining physical activity, stress, and such dietary changes as increased salt intake and decreased intake of calcium and potassium. Increased rigidity of the aorta resulting in reduced compliance is an important hemodynamic feature, but factors that increase peripheral resistance also appear to play a role. Antihypertensive drugs have been shown to effectively and safely lower the systolic blood pressure elevations characteristic of ISH. To date, use of low drug doses and careful titration of dosage have avoided significant orthostatic hypotension and undue lowering of the diastolic pressure. Studies of relatively small groups of patients suggest that antihypertensive drugs can lower the risk of cardiovascular morbidity/mortality associated with ISH but the definitive answer awaits results of the ongoing large-scale Systolic Hypertension in the Elderly Program trial. In the interim, management should begin with conservative measures such as weight loss, salt restriction and, possibly, calcium supplementation. If this fails, drug therapy should be considered in patients with systolic blood pressures above 180 mm Hg and in those with systolic readings between 160 and 180 mm Hg who have concomitant cardiovascular risk factors. To date, no controlled trials of sufficient size have demonstrated that one drug class is more effective than another in treating ISH. Drug therapy should be tailored to the individual patient, starting with a low dose of a single drug and, if necessary, slowly increasing dosage until a systolic blood pressure under 160 mm Hg is attained.

Adult↗
PubMed1991

Comparison of celiprolol and propranolol in stable angina pectoris. Celiprolol International Angina Study Group.

The comparative antianginal effects and safety of propranolol and celiprolol, a highly beta 1-selective adrenoceptor blocker with selective partial beta 2-adrenoceptor agonist activity, were assessed in an international multicenter, placebo run-in, active control, double-blind, randomized, titration-to-effect study of 140 patients with stable, exercise-induced angina pectoris. At baseline, all patients received placebo for 2 weeks, then titrated doses of once-daily celiprolol (200, 400, 600 mg) or twice-daily propranolol (total daily dose 80, 160, 320 mg) over 4 weeks, followed by a 2-week maintenance period. Heart rate and blood pressure, at rest and with exercise, weekly anginal attack frequency, nitroglycerin consumption and symptom-limited treadmill exercise times (modified Bruce protocol) were assessed. Compared with their respective baselines, both celiprolol and propranolol reduced anginal attack and nitroglycerin consumption rates to a comparable degree, while improving exercise tolerance (p less than 0.05). Treatment with propranolol compared with celiprolol, however, was associated with a significantly lower heart rate at rest (p less than 0.01). The double-product at the conclusion of exercise testing was significantly reduced by both drugs. Celiprolol and propranolol had similar effects on blood pressure, and were well tolerated. More symptomatic bradycardia occurred with propranolol. Despite the differences in their hemodynamic actions, once-daily celiprolol is as effective as twice-daily propranolol in the treatment of patients with stable angina pectoris.

Adrenergic beta-Antagonists↗
PubMed1991

Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins.

Fibric acid derivatives (FADs) are a class of drugs that have been shown to reduce the production of very low-density lipoprotein (VLDL) while enhancing VLDL clearance due to the stimulation of lipoprotein lipase activity. The drugs can reduce plasma triglyceride levels while raising high-density lipoprotein (HDL) cholesterol levels. Their effects on low-density lipoprotein (LDL) cholesterol levels are less marked and more variable. There is evidence that oral gemfibrozil (Lopid, Parke-Davis, Morris Plains, NJ) can reduce the risk of serious coronary events, specifically in those patients who had elevations of both LDL cholesterol levels and total plasma triglyceride levels with lower HDL cholesterol levels. Newer FADs (bezafibrate, ciprofibrate, fenofibrate) have been shown to have greater efficacy in reducing LDL cholesterol than gemfibrozil but, in general, these drugs are not as effective as the other primary drugs used to lower LDL levels. The FADs are also used to treat adult patients with very high levels of triglycerides who have pancreatitis and whose disease cannot be managed with dietary therapy. The FADs are well tolerated, with dyspepsia and abdominal pain the most common adverse effects. A small risk of cholelithiasis exists with these drugs, and caution should be used when combining these drugs with HMG-CoA reductase inhibitors because the combination increases the incidence of hyperlipidemic myositis and rhabdomyolysis.

Bezafibrate↗
PubMed1991

Nicotinic acid for the treatment of hyperlipoproteinemia.

Nicotinic acid is a water-soluble B-complex vitamin that has been shown, in high doses, to lower total plasma cholesterol (C), LDL-C, and VLDL-triglycerides (Tg), while raising HDL-C in patients with type II, III, IV, and V hyperlipoproteinemia. Its exact mechanism of action is not known, but it appears to lower the production of VLDL in the liver while activating lipoprotein lipase. The drug may also influence the metabolism of HDL-C. The drug is a second or third choice for isolated hypercholesterolemia because of a high incidence of side effects. However, it has a therapeutic advantage as a monotherapy when reduction of both LDL-C and triglycerides are needed in patients with severe combined hyperlipidemia. The drug can be used in combination with other cholesterol-lowering agents to maximize lipid-lowering activity. Nicotinic acid has been associated with a reduced risk of cardiovascular morbidity in clinical trials.

Anticholesteremic Agents↗
PubMed1991

Neutral endopeptidase inhibitors and atrial natriuretic peptide.

A limited number of ectoenzymes appear to be involved in the inactivation of circulating-regulatory peptides. Neutral endopeptidase 24.11, a metallopeptidase, is known to inactivate atrial natriuretic peptide (ANP), a substance with diuretic, natriuretic, and vasodilatory effects. Synthetic inhibitors of endopeptidase 24.11, which can prolong the activity of ANP, are currently available. These agents are being evaluated as possible innovative therapies for patients with hypertension and congestive heart failure.

Animals↗
PubMed1991

Clinical perspective on celiprolol: cardioprotective potential.

beta-Adrenergic blockers have had widespread use in the treatment of cardiovascular disease. Some agents of this class have been shown to reduce the incidence of total mortality, cardiovascular mortality, sudden death, and nonfatal reinfarction in survivors of acute myocardial infarction. The mechanism for this cardioprotective action is not known. Antiarrhythmic action and hemodynamic alterations have been suggested as possible mechanisms. An anticoagulant mechanism is another possibility, although the antiplatelet effects of beta-blockers are weak. It is now believed that antithrombotic effects may be related to the prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than a direct anticoagulant action. The therapeutic ability beta-blockers to attenuate the hemodynamic consequences of catecholamine surgers, as they do in aortic dissection, may protect a vulnerable plaque from fracture, reducing the risk of coronary thrombosis, myocardial infarction, and death. Celiprolol, a third-generation beta 1-selective adrenergic blocker with partial beta 2-agonist activity, is comparable to other beta-blockers in antihypertensive and antianginal activity. It has additional actions that may be beneficial to patients: (1) it does not adversely affect lipids and lipoproteins; (2) it does not appear to depress the myocardium in patients with left ventricular dysfunction; (3) it can lower serum fibrinogen levels; and (4) it can cause regression of myocardial mass in patients with left ventricular hypertrophy.

Adrenergic beta-Antagonists↗
PubMed1991

Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril.

This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double-blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ.

Administration, Oral↗
PubMed1991

Effects of labetalol on perioperative stress markers and isoflurane requirements.

We have studied the effect of labetalol on anaesthetic requirements, cardiac and humoral responses in 16 healthy women during elective abdominal surgery. The experimental group (n = 8) received increments of i.v. labetalol 0.15-0.3 mg kg-1 to reduce mean arterial pressure (MAP) by 15% from values obtained before anaesthesia. All patients received thiopentone 6 mg kg-1 and anaesthesia was maintained with isoflurane and nitrous oxide. In the placebo group, tracheal intubation provoked a 33% increase in heart rate (HR) and a 52% increase in MAP (P less than 0.001 vs baseline for both). In contrast, pretreatment with labetalol resulted in a 7.3% increase in HR and a 21.3% increase in MAP (P less than 0.05 vs baseline for MAP). Two patients treated with labetalol had a reduction in MAP to 50-60 mm Hg during surgery. After tracheal extubation, the labetalol group had a significantly slower HR than the placebo group (P less than 0.05). The cardiovascular response to tracheal intubation was associated with an increase in plasma noradrenaline concentration in both groups. Labetalol did not affect isoflurane requirements, plasma concentrations of adrenaline, cortisol and aldosterone or arterial PO2, but prevented the decrease in plasma concentration of potassium which occurred in placebo treated patients (P less than 0.05) in early recovery. We conclude that preanaesthetic administration of labetalol attenuated the perioperative hypertensive and tachycardic responses, but was accompanied by intraoperative hypotension when given in doses greater than 0.5 mg kg-1, despite an increase in plasma noradrenaline concentrations.

Abdomen↗