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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 127 records · Page 7Linked to original sources

Beta-adrenergic blockade in the prevention of myocardial infarction: a new theory.

Beta-adrenergic blockers have a protective effect in reducing mortality in survivors of myocardial infarction. It is proposed that, in addition to their effects in reducing heart rate, blood pressure, myocardial contractility and ventricular ectopy, beta-blockers may prevent or attenuate the fracture of vulnerable atherosclerotic plaques and thereby reduce coronary thrombosis, myocardial infarction and sudden cardiac death.

Adrenergic beta-Antagonists↗

Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents.

beta-Adrenergic blockade has provided one of the major pharmacotherapeutic advances of this century. The drugs in this class have the common property of blocking the binding of catecholamines to beta-adrenergic receptor sites; however, there are pharmacodynamic and pharmacokinetic differences between the individual agents which are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing beta-blockers are currently in use, and ultrashort-acting agents are also available. The pharmacokinetics of beta-blocking drugs can also be influenced by race, age, cigarette smoking and concomitant drug therapy. The wide interpatient variability in plasma drug concentration observed with beta-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among the beta-blockers, these drugs should always be titrated in the individual patient to achieve the desired clinical response.

Adrenergic beta-Antagonists↗

Medical therapy of the hypertensive patient with concomitant angina pectoris.

Systemic hypertension and symptomatic ischemic heart disease are two common disorders that coexist in the same patient. A medical approach to the patient with both systemic hypertension and angina pectoris is presented in this article, and different treatment modalities are considered.

Adrenergic beta-Antagonists↗

The interplay of ischemic and hypertensive pathophysiology on cardiac function.

Many patients with systemic hypertension also have concomitant angina pectoris. Hypertension is a risk factor for the development of coronary artery disease as well as an aggravating factor once symptomatic ischemic heart disease develops. It would be prudent to use one agent that reduced the elevated blood pressure and relieved anginal symptoms while providing no negative affects on hemodynamics or other cardiac risk factors. beta-Adrenergic blockers (traditional agents and newer compounds with ancillary properties) and calcium-entry blockers have been shown to be effective as monotherapies in patients with angina. They also have the ability to induce left ventricular hypertrophy regression. There is some evidence that some of these therapies may arrest the development of arteriosclerosis and may have an inhibitory effect on platelet aggregation. What remains controversial is the optimal amount of blood pressure reduction in patients with hypertension coexistent with angina, or whether one specific agent or drug class would have an overall advantage in reducing the risk of morbidity or mortality.

Adrenergic beta-Antagonists↗

Reduction of mortality, sudden death and non-fatal reinfarction with beta-adrenergic blockers in survivors of acute myocardial infarction: a new hypothesis regarding the cardioprotective action of beta-adrenergic blockade.

Beta-adrenergic blockers have been shown definitely to reduce the incidence of total mortality, cardiovascular mortality, sudden death and nonfatal reinfarction in survivors of an acute myocardial infarction. The mechanisms to explain this protective action of beta blockers have never been elucidated conclusively, and include the antiarrhythmic and myocardial oxygen demand-reducing effects of the drugs. An antithrombotic mechanism has also been suggested. However, beta blockers have relatively weak antiplatelet activity, suggesting that their antithrombotic effects may be related to prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than direct anticoagulant action. The therapeutic ability of beta blockers to attenuate the hemodynamic consequences of catecholamine surges, may protect a vulnerable atherosclerotic plaque from fracture, thereby reducing risk of coronary thrombosis, myocardial infarction and death.

Adrenergic beta-Antagonists↗

Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.

The prevalence, incidence and prognosis of recognized and unrecognized Q-wave myocardial infarction (MI) was assessed in an 8-year prospective study of 390 community-based subjects (age 75 to 85 years at entry, mean 79 years). Subjects were studied at baseline and with annual follow-up electrocardiographic (ECG) exams. At baseline, 7.9% had a history of MI without ECG evidence, 6.4% had ECG evidence of Q-wave MI without clinical history, 4.1% had both clinical history and ECG evidence and 81.5% had neither history nor ECG evidence (control subjects). After an average follow-up period of 76.2 months, the total mortality rate was 5.9/100 person-years for subjects with some evidence of MI at baseline versus 3.9 in the control group (p = 0.059). The incidence of cardiovascular disease in subjects with evidence of MI was 8.8/100 person-years versus 4.7 among control subjects (p = 0.002). During the follow-up period, 115 new Q-wave MIs occurred (50 unrecognized, rate 2.4/100; 65 recognized, rate 3.2/100). There was no difference in mortality and morbidity outcome between subjects with recognized and unrecognized MIs. Those with only a history of MI at baseline had a threefold greater risk of a new MI (recognized and unrecognized) than the control group (p = 0.003). Unrecognized Q-wave MI is a common occurrence in the "old old" with subsequent morbidity and mortality prognosis comparable to that of recognized MI. History of MI alone in this age group is also associated with an increased risk of MI, suggesting the need for better diagnostic markers of myocardial ischemia in the old.

Aged↗

The safety and efficacy of quinapril in the treatment of mild to moderate essential hypertension.

Major clinical trials are reviewed comparing the efficacy and safety of quinapril hydrochloride, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, with that of placebo, captopril, and enalapril in the treatment of mild to moderate essential hypertension. A randomized, double-blind 12-week study of 270 patients compared the efficacy of placebo with once or twice daily doses of quinapril (20, 40, 80 mg/day, with forced titration). Quinapril effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure. Mean reductions in DBP of up to 13 mmHg from baseline were obtained. At full dosage, more than 65% of patients achieved a clinically significant reduction in DBP. Quinapril was similarly effective whether the total daily dose was given once or twice daily. In a multicenter, double-blind study involving more than 400 patients, the efficacy of quinapril (10-40 mg/day, given once or twice daily) was found to be similar to captopril (25 mg bid to 50 mg tid). Hydrochlorothiazide (HCTZ) safely provided additive effects when given to nonresponders in both treatment groups. In a 28-week double-blind study of 258 patients comparing the efficacy of quinapril or enalapril at doses of 10, 20, and 40 mg/day (with optional titration), quinapril was found to be of similar efficacy as enalapril. The large majority of patients on either regimen were controlled with monotherapy. HCTZ again safely provided additive effects. Quinapril was well tolerated in all trials, with the incidence of adverse events and withdrawals tending to be lower with quinapril than with enalapril or captopril.

Angiotensin-Converting Enzyme Inhibitors↗

The efficacy and safety of quinapril in the treatment of moderate to severe and severe hypertension: comparison to captopril.

Major studies comparing the efficacy and safety of quinapril and captopril in the treatment of moderate to severe or severe hypertension are reviewed. Given concurrently with hydrochlorothiazide 25 mg/day to patients with moderate to severe hypertension, quinapril 20-80 mg/day twice daily was found to be more effective than captopril 50-200 mg/day twice daily, and quinapril 10-40 mg/day once daily was found to be as effective as captopril 25-100 mg/day twice daily. Given as initial monotherapy to patients with severe hypertension, quinapril 10-40 mg/day twice daily was found to be as effective as captopril 50-200 mg/day twice daily. Quinapril was found to be well tolerated, both when administered against a diuretic background and when diuretic was added to a quinapril regimen.

Angiotensin-Converting Enzyme Inhibitors↗

Co-enzyme Q10: a new drug for cardiovascular disease.

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide.

Administration, Oral↗

Bile acid sequestrants.

The bile acid sequestrants, cholestyramine and colestipol, are the drugs of choice for the treatment of patients with hypercholesterolemia caused by increases in LDL-cholesterol levels without concurrent hypertriglyceridemia (type IIA and type IIB hyperlipoproteinemia). Longitudinal clinical studies with these drugs have shown their ability to slow the progression of atherosclerosis and to limit the consequences of the disease. Bile acid sequestrants can be used with other lipid-lowering drugs such as nicotinic acid or HMG CoA reductase inhibitors, to maximize the cholesterol-lowering effects. The side effect profile of the bile acid sequestrants is tolerable, with most complaints related to effects on the gastrointestinal tract and the bulkiness of the resins.

Chemical Phenomena↗

Rapid-acting parenteral antihypertensive agents.

Parenteral antihypertensive agents are useful in those clinical situations where rapid reduction of blood pressure is necessary or where treatment with oral antihypertensive medications is not feasible. Given the diverse selection of parenteral antihypertensive drugs now available, therapy can be individualized. The presence of concurrent diseases will often influence the decision-making process regarding choice of an agent. Complications of parenteral antihypertensive therapy can arise from the intrinsic properties of the various drugs or the development of severe hypotension. Gradual lowering of blood pressure, in conjunction with careful clinical evaluation, will minimize the risks of acute parenteral antihypertensive therapy. Given that parenteral antihypertensive therapy often needs to be replaced by oral therapy, those drugs that can be used both parenterally and orally may have an advantage.

Antihypertensive Agents↗

Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism.

Penbutolol and carteolol are two new long acting, nonselective beta-adrenergic blockers which have been approved for the treatment of systemic hypertension. Both drugs have intrinsic sympathomimetic activity (partial agonist activity), however, less than that seen with pindolol. They appear to cause less resting bradycardia than propranolol, have no effect on lipids and lipoproteins, and have favorable side effect profiles.

Arrhythmias, Cardiac↗

Betaxolol: a new long-acting beta 1-selective adrenergic blocker.

Betaxolol (Searle, Skokie, Illinois) is a new beta 1-selective adrenergic blocker with no partial agonist action and minimal membrane stabilizing activity. Its pharmacokinetic profile is characterized by a long serum half-life and excellent oral bioavailability, with little first-pass metabolism. The mean 16-hour half-life of betaxolol has been shown to provide full 24-hour control of blood pressure and heart rate. Betaxolol has been proven to be a safe and effective antihypertensive agent, and was recently approved for clinical use in the United States for this indication.

Adult↗

Dietary fiber for reducing blood cholesterol.

Soluble dietary fiber, including psyllium, has been shown to have mild to modest cholesterol lowering properties. Psyllium hydrophilic mucilloid (Metamucil, Procter and Gamble, Cincinnati, OH), a bulk laxative, when used as a dietary supplement in combination with a low fat diet, can lower total serum cholesterol and low-density lipoprotein (LDL) cholesterol, and raise high-density lipoprotein (HDL) cholesterol in hypercholesterolemic patients. The cholesterol lowering effects of psyllium are much less evident than those observed with cholestyramine and the HMG-CoA reductase inhibitors. The mechanism for the cholesterol lowering effect of psyllium is not known. The substance is well tolerated with long-term use.

Cholesterol↗

Women, myocardial infarction, and dementia in the very old.

Dementia is a major public health problem among the very old. Available information on incidence and prevalence is sparse and variable; however, there appears to be a higher prevalence among very old women. We present data from a prospective study of initially nondemented community-residing elderly. There were 75 incident dementia cases (up to 7 years of follow-up) of which at least 47% were probable Alzheimer's disease. Based on a proportional hazards analysis, women were over 3 times more likely to develop dementia than men despite controlling for baseline demographic, psychosocial, and medical history variables. Poor word fluency and a high normal Blessed test score at baseline were also strong predictors of dementia. We did not find age, head trauma, thyroid disease, or family history of dementia to be risk factors. A new finding is that history of myocardial infarction (MI) is associated with dementia, such that women with a history of MI were 5 times more prone to dementia than those without a history. This observation was not true for men.

Aged↗

Clinical use of beta-adrenoceptor blockade in systemic hypertension.

beta-Blockers are effective in reducing the blood pressure of many patients with systemic hypertension. They differ in terms of the presence or absence of intrinsic sympathomimetic activity, membrane-stabilising activity, beta 1-selectivity, alpha-blocking properties, and relative potency and duration of action. All beta-blockers appear to have blood pressure lowering effects. The choice of which beta-blocker to use in an individual patient is determined by the pharmacodynamic and pharmacokinetic differences between the drugs in conjunction with the patient's other medical condition(s). This review discusses the practical use of beta-blockers and provides rational suggestions for which drug(s) to use in selected patient groups (Black, elderly, postinfarction, diabetes, renal disease, obstructive lung disease, elevated lipid levels, coexisting angina, and left ventricular hypertrophy).

Adrenergic beta-Antagonists↗

The nifedipine gastrointestinal therapeutic system in the treatment of hypertension.

As the number of antihypertensive agents increases, the choice of optimal therapy becomes more difficult. Certainly, hemodynamic derangements caused by the disease state as well as therapy must be considered. Patient convenience and quality of life are also issues that must be addressed. Preliminary experience suggests that the gastrointestinal therapeutic system (GITS) push-pull osmotic pump formulation of nifedipine is safe and efficacious in the treatment of hypertension. In 1 study, nifedipine GITS was compared with sustained-release propranolol in patients with mild to moderate hypertension already receiving diuretics. Using a 2-week placebo run-in, double-blind study design, patients were randomly assigned to receive nifedipine GITS (n = 31) in doses of 30, 60 or 90 mg once daily, or sustained-release propranolol (n = 32) in doses of 80, 160 or 240 mg once daily. Previous diuretic therapy was continued. Sitting and 5-minute standing blood pressure and heart rate measurements were obtained 24 hours after dosing. At the end point of treatment, both nifedipine GITS and sustained-release propranolol reduced blood pressure compared with placebo (p less than 0.001) in the sitting and standing positions. Nifedipine GITS was more effective than sustained-release propranolol in reducing standing (p less than 0.005) and sitting (p less than 0.001) systolic blood pressure and sitting diastolic blood pressure (p less than 0.02). Sustained-release propranolol caused a greater reduction in standing (p less than 0.001) and sitting (p less than 0.0006) resting heart rate than nifedipine GITS. Both drugs were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Pharmaceutical↗