Search PubMed⌕ Search

Biomedical subjects

M A Klausner

Publications and source records attributed to M A Klausner.

9 recordsLinked to original sources
PubMed1988

Antihypertensive efficacy of cetamolol: a dose-titrated study.

This double-blind, placebo-controlled, randomized multicenter study evaluated the antihypertensive efficacy and safety of cetamolol hydrochloride in 108 patients diagnosed as having mild to moderate hypertension. After a placebo lead-in period, patients received either cetamolol 5-10-15 mg/d (low dose), cetamolol 15-25-50 mg/d (high dose), or placebo, once daily for four weeks. Patients began at the lowest dose and were titrated to higher doses based on the first two assessments of diastolic blood pressure and heart rate, which were conducted each week after double-blind treatment was dispensed. After four weeks of treatment 82.4%, 81.3%, and 93.3% of the low-dose group, high-dose group, and placebo group, respectively, were titrated to the maximum dose level. After four weeks of treatment and 24 hours since the patient's last dose, both cetamolol groups showed a significantly greater (P less than or equal to .05) reduction in supine systolic/diastolic blood pressure (-18.1 +/- 2.3/-9.2 +/- 1.5 mm Hg [low dose] and -17.3 +/- 2.3/-8.3 +/- 1.6 mm Hg [high dose]) than the placebo group (-9.9 +/- 2.5/-3.5 +/- 1.7 mm Hg). In general, the changes in standing (stabilized) systolic and diastolic blood pressure were similar to those seen in supine measurements. Significantly more patients receiving cetamolol than those receiving placebo showed a "good response" (a decrease in diastolic blood pressure of 10 mm Hg or more or measuring less than 90 mm Hg with a decrease of at least 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗
PubMed1988

Cardioselectivity of cetamolol compared with atenolol and nadolol.

The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

Acetamides↗
PubMed1988

Effect of cetamolol on epinephrine-induced hypokalemia.

The effect of cetamolol (an investigational cardioselective beta blocker with intrinsic sympathomimetic activity) on the hypokalemic response to epinephrine infusions in normal subjects was evaluated and compared with placebo and two other beta-adrenergic blocking drugs. After two daily doses of cetamolol 15 mg, atenolol (a cardioselective beta blocker) 50 mg; a long-acting propranolol preparation (a nonselective beta blocker) 80 mg; or placebo, 12 men (mean age, 26.7 years) were infused with epinephrine. The resulting average plasma epinephrine level was 1123 pg/mL, whereas average baseline serum potassium levels for the four treatment groups ranged from 3.94 to 4.07 mEq/L. Epinephrine-induced hypokalemia occurred in the placebo group (maximum potassium decrease of 1.00 mEq/L) and in the atenolol group (maximum potassium decrease of 0.59 mEq/L); potassium levels did not decrease but rose slightly in subjects receiving cetamolol or propranolol. Subjects treated with placebo or atenolol also demonstrated statistically significant prolongation of the QTc interval (0.039 seconds with placebo; 0.023 seconds with atenolol) and frequently developed T-wave flattening and U-wave appearance. After pretreatment with cetamolol or propranolol, however, the QTc interval was unaffected, T-wave abnormalities did not occur, and U waves appeared only rarely. The results of this study indicate that cetamolol blocks epinephrine-induced hypokalemia and associated electrocardiographic changes.

Acetamides↗
PubMed1988

Pharmacokinetics of cetamolol in hypertensive patients with normal and compromised renal function.

The efficacy, safety, and pharmacokinetic parameters of a 30-mg oral dose of cetamolol hydrochloride (Betacor), a new synthetic cardioselective beta-adrenoceptor antagonist, with intrinsic sympathomimetic activity, were evaluated by studying 32 hypertensive patients with normal renal function or different degrees of renal impairment. After administration of cetamolol, serial blood and urine sample collections, as well as vital sign determinations for the next 48 hours, were performed in all patients (with the exception of urine collection, which was not possible in hemodialysis patients). Results indicate that cetamolol's pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment. Specifically, as the severity of renal impairment increased, the maximum serum concentration (Cmax) and the area under the serum concentration-time curve (AUC) increased, whereas the renal clearance (CLR), urinary excretion, and total body clearance (CL) decreased. Additionally, significant direct or inverse correlations for AUC, CL, CLR, and urinary excretion with creatinine clearance (CLCR) were demonstrated. In the subjects with mild renal impairment, the trends toward changes in the cetamolol pharmacokinetic parameters were evident, though small and not statistically significant. Although anuric, patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about one-third of that found in normal subjects. Reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of renal impairment increased. There were no adverse drug or toxic effects noted in any of the study patients. Based on these findings, dosing recommendations are suggested for patients who have compromised renal function because of the effects of renal function on the pharmacokinetics of cetamolol.

Acetamides↗
PubMed1975

Contrasting splenic mechanisms in the blood clearance of red blood cells and colloidal particles.

We have studied the blood clearance and organ uptake of colloidal particles and of antibody-coated and chemically treated Na2 51Cr O4-labeled erythrocytes (RBC) in mice. Hepatic and splenic uptake of both colloidal particles and autologous RBC coated with rabbit antibody were reduced significantly following pretreatment of animals with cortisone acetate. Hepatic removal of RBC previously treated in vitro with N-ethyl-maleimide (NEM) or phenylhydrazine-HCl (PHZ) was similarly depressed by pretreatment with cortisone. In contrast, the splenic uptake of NEM- and PHZ-altered erythrocytes was unaffected by cortisone. Scanning and transmission electron microscopic examination of perfused spleens from PHZ-injected animals demonstrated extensive mechanical trapping of Heinz body-containing RBC in sinus wall apertures, whereas little erythrophagocytosis was observed. These studies suggested that, while clearance of inert particulate matter and of antibody-coated RBC from the blood occurred primarily by a cortisone-suppressible, presumably phagocytic process in the spleen, chemically altered RBC were removed primarily by a cortisone-insensitive filtration process in the splenic microvasculature.

Animals↗