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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 163 records · Page 9Linked to original sources
PubMed1989

Profile of an ideal antianginal agent.

Many antianginal agents are available for the treatment of coronary artery disease. These agents act by influencing the determinants of myocardial oxygen supply and demand. The 3 main classes of agents are the nitrates, beta-adrenergic blocking agents and the calcium entry blockers. Agents from all 3 classes have shown efficacy in treating both symptomatic and asymptomatic myocardial ischaemia. However, some patients cannot be treated with these agents because of side effects or contraindications. An ideal antianginal drug should effectively treat both angina and silent ischaemia. Additionally, it should be free of side effects, allow for maintenance of physical performance and be metabolically neutral. New agents are being developed which strive for this goal.

Adrenergic beta-Antagonists↗
PubMed1989

Clinical performance and therapeutic potential of celiprolol in angina pectoris.

Celiprolol, a long-acting, beta 1-selective adrenergic blocking drug, with peripheral beta 2-stimulatory and peripheral alpha 2-inhibitory action, has a unique pharmacologic profile. Its antianginal properties have been evaluated in comparison with those of propranolol and atenolol. Efficacy was assessed by improvement in time to exercise-limiting angina and to onset of ST-segment depression, as well as by symptomatic improvement. Celiprolol has been demonstrated to have antianginal and anti-ischemic effects comparable with both propranolol and atenolol, with a decreased incidence of bradycardia noted in the celiprolol-treated cohorts. No significant adverse effects or laboratory abnormalities were noted in these cohorts. Current indications for beta-blocker therapy are numerous. Cardioprotective effects and reduction in ischemic potential have been identified in a variety of clinical settings. Decreased morbidity and mortality in the postinfarct period have been well documented. Effects on supraventricular and ventricular arrhythmias, in the presence or absence of ischemia, are well known. Favorable hemodynamic effects in the peri- and postoperative period of coronary artery bypass surgery are described. More recently, beta-blocker therapy that is effective against angina has also been demonstrated effective in the reduction of silent ischemia. The different hemodynamic properties of the newer beta-blockers may provide additional therapeutic effects in many clinical situations.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of calcium entry blockade on hypertension-induced left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is a structural adaptation of the heart and is a response to increased hemodynamic and metabolic demands, which are most commonly caused by systemic hypertension. LVH induced by hypertension is associated with reduced myocardial compliance, structural alterations, and changes in coronary perfusion. Calcium entry blockers have caused LVH regression both in experimental studies and in clinical trials. Although their efficacy as antihypertensive agents is primarily due to their vasodilating properties, the mechanisms by which calcium entry blockers accomplish LVH regression are complex and include various hemodynamic and neurohumoral factors. Calcium entry blockade has decreased LVH with no apparent deterioration of left ventricular function. Because LVH is a major risk factor for sudden cardiac death and other cardiac morbidities, it is possible that the regression of LVH can improve the prognosis in hypertensive patients.

Animals↗
PubMed1989

Calcium channel blockers in myocardial infarction.

Calcium channel blockers are currently approved for use in patients with arrhythmias, stable and unstable angina pectoris, and systemic hypertension. The hemodynamic and electrophysiologic properties of these agents suggest that their use would be appropriate in both the immediate and the long-term management of patients who suffered a myocardial infarction. Some experimental evidence accumulated from animal models supports the ability of these drugs to reduce both myocardial infarct size and the incidence of ventricular arrhythmias. The clinical trials with these drugs, however, have yielded disappointing results. Some data suggest a role of diltiazem therapy in reducing the incidence of transmural wall infarction and angina in those patients sustaining non-Q-wave myocardial infarctions. In the setting of Q-wave infarction, calcium channel blockers seem to be less effective than beta-blockade both for acute and long-term management. Finally, calcium channel blockers appear to be contraindicated in patients who have suffered a myocardial infarction and who have concomitant left ventricular dysfunction.

Calcium Channel Blockers↗
PubMed1988

Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol.

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.

Adrenergic beta-Antagonists↗
PubMed1988

Hemodynamic effects of flestolol, a titratable short-acting intravenous beta-adrenergic receptor blocker.

The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients.

Adrenergic beta-Antagonists↗
PubMed1988

Controlled beta-receptor blockade with esmolol and flestolol.

Beta-receptor-blocking agents are commonly used in the management of various cardiovascular diseases. Recently, esmolol, a pharmacokinetically novel cardioselective beta-receptor-blocking agent, has been introduced for use in the treatment of critically ill patients. It is devoid of intrinsic sympathomimetic activity and in doses used clinically, it has no direct depressant effect on the heart. Esmolol is an ester and is metabolized by choline-esterase to ASL 8123, an inactive molecule. Esmolol has an elimination half-life of nine minutes which accounts for its ultrashort duration of action. This unique pharmacokinetic property provides two advantages over other longer-acting beta-receptor-blocking agents. First, the magnitude of beta-receptor blockade can be titrated to a desired level. Second, if adverse effects are experienced, reducing the dosage or terminating the infusion results in rapid reversal of its pharmacological effects. Another ultrashort-acting, non-cardioselective beta-receptor blocking agent, flestolol is undergoing clinical evaluation. Esmolol has been approved for the management of supraventricular tachycardia. The clinical safety of these novel drugs will expand the use of beta-receptor-blocking agents in the management of cardiovascular diseases in critically ill patients.

Adrenergic beta-Antagonists↗
PubMed1988

Properties of labetalol, a combined alpha- and beta-blocking agent, relevant to the treatment of myocardial ischemia.

Labetalol, a combined alpha-beta-adrenergic antagonist, is one of the new group of beta-adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike alpha-adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to alpha- and beta-adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications.

Adrenergic alpha-Antagonists↗
PubMed1988

Circulatory and metabolic aspects of beta-adrenoceptor blockade.

beta-Blocking therapy is used extensively is conditions as diverse as hypertension, angina pectoris, arrhythmias, thyrotoxicosis, hypertrophic cardiomyopathy, migraine, glaucoma, and myocardial infarction. Studies show they beneficially influence sinus node and atrioventricular conduction, but excessively high doses may cause sinus arrest or sinoatrial block. Nonselective beta-blockade in asthmatic patients may aggravate bronchoconstriction, whereas increased airways resistance is less likely with beta 1-selective, partial agonist, or alpha-beta-blocking drugs. Hypoglycemia can be prolonged; beta 1-selective or partial agonist drugs may cause less interference with glucose metabolism. beta-Blockade affects free fatty acids, lipids and lipoproteins, thyroid hormones, and parathormone. beta-Blockade may normalize abnormal platelet aggregation. Finally, the choice of the most effective drug depends on the clinician's knowledge of the various pharmacodynamic and pharmacokinetic drug profiles, allied with familiarity of the patient's medical condition.

Adrenergic beta-Antagonists↗
PubMed1988

Celiprolol in angina pectoris.

Celiprolol, a long-acting beta1-selective adrenergic-blocking drug with peripheral beta2-stimulatory and peripheral a2-inhibitory activities, has a unique vasodilator beta-blocker pharmacologic profile. The efficacy and safety of celiprolol in angina pectoris have been demonstrated in multiple studies that highlight its different hemodynamic properties compared with traditional beta-blockers. Celiprolol was found to be an effective antianginal agent compared with placebo. In addition, in angina and ischemia its efficacy was comparable to that of propranolol and atenolol.

Adrenergic beta-Antagonists↗
PubMed1988

Atrial infarction: diagnosis and management.

Atrial infarction has been a relatively understudied entity. Its incidence by autopsy study has been widely variable, from 0.7% to 42%, with the largest series of 182 patients demonstrating an incidence of 17%. The right atrium is involved five times as often as the left, with the auricle the predominant site in either atria. Clinical atrial infarction may present with supraventricular arrhythmias, atrial rupture, hemodynamic compromise from loss of atrial "kick," and thromboembolic phenomena. Diagnosis currently is made in an appropriate clinical setting with characteristic PR interval changes. Other noninvasive techniques have shown only limited diagnostic utility, but esophageal echocardiography may prove to be a useful technique in this setting.

Arrhythmias, Cardiac↗
PubMed1988

Hormonal and metabolic effects of calcium channel antagonists in man.

Calcium is a component of many metabolic reactions. By blocking calcium transport across cell membranes, calcium channel antagonists can therefore theoretically affect numerous metabolic and hormonal processes. In vitro studies have often documented just such an effect. Because of the expanding use and prevalence of calcium antagonists in clinical practice, a review of their in vivo effects on hormones and metabolism is warranted. The effect on glucoregulatory hormones, calcium regulatory hormones, anterior and posterior pituitary secretion, the renin-angiotensin axis, plasma catecholamines, and plasma lipids and lipoproteins is herein reviewed. The various calcium antagonists, by virtue of their distinct chemical structures, influence metabolism in their own unique manner. Despite the widespread involvement of calcium in hormone action, however, calcium channel antagonists have little dramatic impact on hormone regulation. This is, in part, due to the drug dosage used in clinical practice and to the inherent compensatory mechanisms built into normal endocrine function. The development of agents with greater and more potent metabolic specificity, however, coupled with the ability to target drug action, holds promise for expanded therapeutic application in the future.

Adrenal Cortex Hormones↗
PubMed1988

Ultra-short-acting beta-adrenergic blockers.

The ultra-short-acting beta-adrenergic blockers are parenteral agents that can be rapidly titrated in clinical situations where immediate beta-adrenergic blockade is warranted. The effects of those drugs rapidly dissipate after termination of treatment, providing an important safety feature. Esmolol, the prototype drug of this class, is approved for treatment of supraventricular tachyarrhythmias but also has potential use in treatment of patients with perioperative hypertension and acute myocardial ischemia.

Adrenergic beta-Antagonists↗
PubMed1988

Alpha-adrenergic blockers.

alpha-Adrenergic blockers are important drugs in the treatment of hypertension and other cardiovascular and noncardiovascular disorders. The ability to selectively block alpha-receptor subtypes provides a greater margin of safety and efficacy for these drugs.

Adrenergic alpha-Antagonists↗
PubMed1988

Terazosin: a new long-acting alpha 1-adrenergic antagonist for hypertension.

Terazosin is a new long-acting, selective alpha 1-adrenergic antagonist. Its pharmacokinetic and pharmacodynamic profiles are similar to those of prazosin, but terazosin has a half-life three to four times longer. This allows once daily dosing of terazosin and a potential advantage in ensuring patient compliance to treatment. Terazosin has been evaluated alone and in combination with other drugs for the treatment of mild to moderate hypertension. Terazosin has been shown to have favorable lipid and side effect profiles. Unlike prazosin, the drug is available (but not yet marketed) in parenteral form. Its gradual onset of action with intravenous use would limit its potential application in hypertensive emergencies. Other possible uses for terazosin might include treatment of congestive heart failure and Raynaud's phenomenon, but definitive studies are needed.

Adrenergic alpha-Antagonists↗
PubMed1988

Calcium channel blockers in systemic hypertension.

Alterations in transmembrane flux of calcium ions may be playing a role in the pathophysiology of systemic hypertension. Calcium channel blockers have been shown to be effective antihypertensive drugs with excellent safety profiles. They are efficacious in the long term treatment of systemic hypertension in all population subgroups, and have special applicability for treating patients with hypertensive urgencies and individuals with concomitant diseases such as angina pectoris and arrhythmias.

Animals↗