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  • Articles  (65)
  • propranolol  (61)
  • Chemical Engineering
  • Electronic structure and strongly correlated systems
  • Saccharomyces cerevisiae
  • Springer  (65)
  • 1980-1984  (65)
  • Medicine  (63)
  • Physics  (2)
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  • Articles  (65)
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  • 1
    Electronic Resource
    Electronic Resource
    Inhibition ofSaccharomyces cerevisiae division by 5-trifluoro-methyl-6-azauracil (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1159-1161 
    Details
    ISSN: 1420-9071
    Keywords: Saccharomyces cerevisiae ; 5-trifluoromethyl-6-àzauracil ; yeast cell cultures ; cell division ; inhibition of
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Cell division, as studied in asynchronous cultures of yeast cells, is sensitive to 5-trifluoromethyl-6-azauracil (F3CAzU). Under defined conditions (10 mmoles l−1 F3CAzU) this compound blocks immediately and completely the process of cell division. Using synchronized cells, the time-point at which division process of yeast cell can be inhibited by F3CAzU has been determined. The inhibitor effect of this compound is completely reversed by thymine, thymidine and uracil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01971472
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  • 2
    Electronic Resource
    Electronic Resource
    Influence of intravenous β-adrenergic blockade with or without partial agonist activity upon plasma cyclic AMP and catecholamines in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 695-698 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; oxprenolol ; partial agonist activity ; cyclic AMP ; plasma catecholamines ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomised within-subject double-blind study, 7 healthy male volunteers, aged 32 to 40 years, received at rest intravenous infusions of 2 mg propranolol (devoid of partial agonist activity), 2 mg oxprenolol (with partial agonist activity) and placebo. Cuff blood pressure did not vary after any of the 3 treatments. The heart rate did not change after placebo, but fell in the first 5 min both after propranolol and oxprenolol (p〈0.01); the rate was slightly lower after propranolol than oxprenolol (p〈0.05). The heart rate remained lower after both β-blockers than placebo from 5 to 60 min after the infusion (both p〈0.01), but the difference between the two β-blockers was no longer significant. Plasma cyclic AMP showed a peak rise at 2 and 3 min after oxprenolol, and remained unchanged at those times after propranolol and placebo. From the 5th to the 60th min after infusion, the cyclic AMP concentration was lower after both β-blockers than placebo, and with a slightly but not significantly higher level on oxprenolol than propranolol. Plasma noradrenaline and adrenaline were higher after the β-blockers compared to placebo. Oxprenolol evoked a smaller and non-significant rise in both catecholamines. That oxprenolol, unlike propranolol, causes a sudden rise in plasma cyclic AMP soon after an i.v. infusion may be due to its partial agonist activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541927
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  • 3
    Electronic Resource
    Electronic Resource
    Is the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds relevant in acute myocardial infarction? (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 509-515 
    Details
    ISSN: 1432-1041
    Keywords: beta-receptor blocking drugs ; myocardial infarction ; haemodynamic effects ; propranolol ; pindolol ; intrinsic sympathomimetic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relevance of the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds to the clinical therapeutics of acute myocardial infarction was evaluated in 20 patients with an uncomplicated acute myocardial infarction by comparing the haemodynamic effects of equivalent beta-blocking doses of propranolol (non-cardioselective; no ISA) and pindolol (non-cardioselective; 50% ISA). Consecutive eligible male patients admitted to a Coronary Care Unit were randomised following a 1 h control period to two separate studies. In Study 1 the short-term dose-response effects of propranolol (1–8 mg) or pindolol (0.1–0.8 mg) were assessed. In Study 2 comparison of the effects of single i.v. propranolol (8 mg) and pindolol (0.8 mg) doses was undertaken over 6 h. Haemodynamic variables and thermodilution cardiac output were subsequently recorded to compare the effects of each drug on the circulation. The plasma concentrations of propranolol and pindolol were in the recognised therapeutic range. Both drugs were clinically well-tolerated, the changes induced in haemodynamic variables following each drug demonstrated effective beta-blockade. Within the limits of the experimental protocol, these data did not suggest definite haemodynamic advantage for ISA of pindolol in acute myocardial infarction. These findings are perhaps due to sympathetic activation in acute myocardial infarction attenuating the haemodynamic impact of ISA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556884
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 517-523 
    Details
    ISSN: 1432-1041
    Keywords: asthma ; beta-receptor blocking drugs ; cardioselectivity ; metoprolol ; propranolol ; cumulative dosing ; fixed airflow obstruction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on ventilation of the non-selective beta-blocker propranolol, and the relatively cardioselective beta-blocker, metoprolol, were compared in a randomized single-blind crossover study in 16 patients with asthma, bronchitis and emphysema (American Thoracic Society critieria). Group I had “fixed” airways disease with 〈20% improvement in FEV1 following inhaled salbutamol 5 mg by nebuliser. Group II had “reversible” obstruction, 〉20% improvement. Bronchodilator therapy was withheld for 24h with the exception of aerosols which were permitted until 12h before study. After control observations on each of 2 study days, each patient received cumulative dosese of propranolol (maximum 170 mg) and metoprolol (maximum 187.5 mg). Ventilatory function (FEV1, FVC, FEV1%) was assessed at 0, 2, 4, 6 and 8h. In Group I, 2 patients were unable to complete the study. One patient became dizzy with propranolol 70 mg but tolerated metoprolol 187.5 mg. One patient developed wheeze with propranolol 15 mg but tolerated metoprolol 187.5 mg. Metoprolol was tolerated in all 8 patients with “fixed” disease, although FEV1 was reduced by more than 30% in 1 patient. Three patients in Group II did not complete the study because of wheezing following propranolol 10 mg, metoprolol 37.5 mg; propranolol 17.5 mg, metoprolol 37.5 mg; propranolol 45 mg, tolerated metoprolol 187.5 mg respectively. Wheezing responded in all cases to inhaled isoprenaline. The response to either propranolol or metoprolol was unpredictable in patients with “reversible” disease. When wheezing occurred in this group, it developed following small, potentially subtherapeutic doses of each drug. Although metoprolol was better tolerated, the practical benefit of cardioselectivity in those patients with reversible airways disease was negligible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556885
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of propranolol during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556896
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  • 6
    Electronic Resource
    Electronic Resource
    Lack of influence of beta adrenergic blockade on serum potassium during an infusion of potassium (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 425-427 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; potassium infusion ; propranolol ; metoprolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The extent to which the serum potassium rose in a group of six healthy volunteers during an intra-venous infusion of potassium was identical following pretreatment with placebo, low or high dose propranolol and low or high dose metoprolol. Thus in this acute study, we were unable to demonstrate any influence of either selective or non-selective beta adrenergic blockade upon potassium uptake mechanisms. This is in contrast to the effects of beta blockers on potassium reuptake rates noted after exercise and during cardiac surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542135
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  • 7
    Electronic Resource
    Electronic Resource
    The phenomenon of β-adrenergic hypersensitivity following propranolol withdrawal studied in normal subjects (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 423-428 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; beta-adrenoceptor blockade ; withdrawal hypersensitivity ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study was carried out to determine whether beta-adrenergic hypersensitivity occurs in normal subjects following the abrupt withdrawal of the beta-adrenoceptor antagonist propranolol. Sixteen normal subjects took propranolol, orally, 120 mg twice daily for one week. Heart rate and blood pressure were measured supine and standing as well as during exercise. Heart rate was measured during and following the Valsalva manoeuvre. Measurements were made on the last day of the treatment period and on two occasions during the six days following withdrawal. Three subjects were removed from the analysis because of failure to take medication and one more was excluded because of protocol variation. In the remaining twelve, propranolol treatment reduced all parameters measured. Following abrupt withdrawal of the drug, there was no measurable increase in any of the parameters above baseline or placebo values within six days of the withdrawal. These findings, from normal subjects, do not support the phenomenon of beta-adrenergic hypersensitivity following propranolol withdrawal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549589
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of beta-blocking drugs on beta-cell function and insulin sensitivity in hypertensive non-diabetic patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 13-17 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocking drugs ; insulin sensitivity ; pancreatic beta-cell function ; hypertension ; propranolol ; atenolol ; insulin secretion ; plasma GIP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p=0.037 and p=0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p=0.0036 and p=0.0003, respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546701
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  • 9
    Electronic Resource
    Electronic Resource
    Ethanol-induced inhibition of hepatic uptake of propranolol in perfused rat liver and in man (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 209-215 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hepatic drug disposition ; rat liver perfusion ; pharmacokinetics in man ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Studies were conducted to determine the mechanism whereby ethanol alters the hepatic disposition of propranolol. In eight isolated perfused rat livers, ethanol ( $$\bar x$$ =40.1 mmol/l diminished the clearance of dl-propranolol (1.93±0.43 to 1.24±0.22 ml/min/g liver, p〈0.05); increased its t1/2 (12.8±1.5 to 20.7±3.25 min, p〈0.01); and decreased the proportion metabolized (68.7±4.7% to 34.3±10.3%, p〈0.01). These results suggest that ethanol could substantially increase the oral bioavailability of propranolol in humans. However, in normal human volunteers administered 80 mg of propranolol orally, alone, or preceded and followed by ethanol to maintain breath ethanol concentrations of 800–1000 mg/l, increases in propranolol AUC were smaller than anticipated. Seven subjects had increases in free propranolol AUC0–8h (32%, range: 12–61%) (p〈0.05), while total propranolol AUC0–8h increased by a mean 22% (range: −4–+49%). Propranolol free fraction varied with time and was higher after ethanol ( $$\bar x$$ =0.090 vs 0.084) (p〈0.077). The extent of the propranolol-induced slowing of heart rate was not influenced by ethanol (mean decrease from baseline of 13 bpm at peak propranolol effect vs 9 bpm without ethanol); mean heart rates following propranolol with ethanol were higher at all times (mean of 7.5 bpm) (p〈0.001) than after propranolol alone. Ethanol inhibits the hepatic oxidative metabolism of propranolol in vitro; however, any effect on heart rate of higher concentrations of propranolol induced by ethanol in humans is off-set by the cardio-acceleratory effect of ethanol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544047
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  • 10
    Electronic Resource
    Electronic Resource
    Propranolol vs metoprolol vs labetalol: A comparative study in essential hypertension (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 1-6 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blockers ; propranolol ; metoprolol ; labetalol ; exercise ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double blind, within patient investigation of twenty-four patients (nineteen males and five females) with a mean age of 46.3 years (SD 10.9 years) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol, metoprolol and labetalol was carried out. Blood pressure and pulse rate were measured in lying, sitting and standing positions and before, during and after isometric and dynamic exercise. Peak expiratory flow was recorded before and during dynamic exercise. All the active treatments were better than placebo in reducing blood pressure and heart rate. Comparing the effects of treatment, labetalol lowered sitting diastolic pressure significantly more than propranolol and standing diastolic pressure than both propranolol and metoprolol. Metoprolol and propranolol were more effective in reducing heart rate. Propranolol significantly reduced peak flow rate compared to labetalol. During the exercise, both isometric and dynamic, the heart rate and the blood pressure, both systolic and diastolic, of the treated patients were lower than those on placebo. There was little difference between the drugs in the influence on blood pressure, but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546699
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  • 11
    Electronic Resource
    Electronic Resource
    Reduced peripheral vascular symptoms in elderly patients treated with α-methyldopa — A comparison with propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 325-329 
    Details
    ISSN: 1432-1041
    Keywords: alpha-methyldopa ; propranolol ; hypertension ; side effects ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A multicentre study of 6–10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00548762
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  • 12
    Electronic Resource
    Electronic Resource
    Simple and reliable radioreceptor assay for beta-adrenoceptor antagonists and active metabolites in native human plasma (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 545-553 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; radioreceptor assay ; propranolol ; carteolol ; active metabolites ; rat reticulocyte membranes ; CGP 12177
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A radioreceptor assay (RRA) for the assay of beta-adrenoceptor antagonists in native human plasma is described. The hydrophilic antagonist3H-CGP 12177 was used as the radioligand. In contrast to the hydrophobic radioligand3H-dihydroalprenolol, which was investigated in parallel, the beta-adrenoceptor binding of3H-CGP 12177 by rat reticulocyte membranes was found not to be affected by inclusion of increasing proportions (0–66% of incubation volume) of human plasma in the assay. Thus, solvent extraction of drug and/or active metabolites was not necessary to avoid binding of the radioligand tracer to plasma added in the RRA. The assay of unprocessed samples was possible. Drug concentrations in plasma after oral administration of propranolol (240 mg) or carteolol (30 mg) to 6 healthy volunteers were measured by the RRA and in parallel by a chemical method. The results from both methods agreed when the plasma concentration kinetics of propranolol were investigated (elimination half-life: 3.9 h). In contrast, plasma concentrations of carteolol were consistently higher according to the RRA after oral administration of the drug. Identical concentrations, however, were found by the RRA and chemical method using plasma samples spiked with carteolol. Plasma concentrations of carteolol detected by the chemical method decline monoexponentially (elimination half-life: 5.4 h). A similar half-life of elimination for parent drug was found by the RRA (5.9 h), but an additional term describing the appearance of an active metabolite was necessary to account for the biphasic drug elimination (elimination half-life of metabolite: 17.3 h). The latter result is in agreement with the appearance of 8-hydroxy-carteolol as an active metabolite, which shows similar affinity for beta-adrenoceptors as the parent drug. The active metabolite, with a 3-fold longer elimination half-life than the parent drug, will prolong the duration of the clinical effects of orally administered carteolol. In conclusion, the RRA permits the determination of beta-adrenoceptor antagonistic activity in native human plasma at concentrations as low as 0.1-fold the IC50-value of the drug or an active metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556890
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  • 13
    Electronic Resource
    Electronic Resource
    Influence of age on serum protein binding of propranolol (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 251-254 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; plasma protein binding ; age effects ; α1-acid glycoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The extent of propranolol protein binding was determined in three different age groups of healthy drug-free caucasian males. Volunteers selected for study were 6–15 years old, 25–36 years old and 68–76 years old. Ten milliliters of blood were obtained via venipuncture and collected in glass tubes from the subjects after an overnight fast. Binding determinations were performed by equilibrium dialysis using radiolabelled propranolol. Serum albumin and α1-acid glycoprotein concentrations were determined in all subjects by radial immunodiffusion. The results obtained showed wide intersubject variability in the binding ratio of propranolol and serum concentrations of α1-acid glycoprotein. Mean albumin serum concentration was found to be significantly lower in the elderly group as compared to the adult and pediatric groups (p〈0.02). A positive correlation was found between the binding ratio of propranolol and the serum concentration of α1-acid glycoprotein in all the subjects (r=+0.66,p〈0.005). No significant correlation was found between the binding ratio of propranolol and the serum concentration of albumin (r=−0.03,p〈0.88). These data suggest that the extent of propranolol binding is influenced primarily by serum concentrations of α1-acid glycoprotein and not by differences in age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00630294
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  • 14
    Electronic Resource
    Electronic Resource
    Effect of experimental traumatic shock of varied severity and of propranolol on metabolic reaction of leukocytes (1984)
    Springer
    Bulletin of experimental biology and medicine 97 (1984), S. 261-264 
    Details
    ISSN: 1573-8221
    Keywords: stress-resistance ; leukocytes ; traumatic shock ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00800822
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  • 15
    Electronic Resource
    Electronic Resource
    Biogenesis of mitochondria: Defective yeast H+-ATPase assembled in the absence of mitochondrial protein synthesis is membrane associated (1984)
    Springer
    Journal of bioenergetics and biomembranes 16 (1984), S. 561-581 
    Details
    ISSN: 1573-6881
    Keywords: H+-ATPase complex ; assembly defect ; Saccharomyces cerevisiae ; mitochondrial biogenesis ; membrane association
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract We have investigated the extent to which the assembly of the cytoplasmically synthesized subunits of the H+-ATPase can proceed in a mtDNA-less (rho°) strain of yeast, which is not capable of mitochondrial protein synthesis. Three of the membrane sector proteins of the yeast H+-ATPase are synthesized in the mitochondria, and it is important to determine whether the presence of these subunits is essential for the assembly of the imported subunits to the inner mitochondrial membrane. A monoclonal antibody against the cytoplasmically synthesized β-subunit of the H+-ATPase was used to immunoprecipitate the assembled subunits of the enzyme complex. Our results indicate that the imported subunits of the H+-ATPase can be assembled in this mutant, into a defective complex which could be shown to be associated with the mitochondrial membrane by the analysis of the Arrhenius kinetics of the mutant mitochondrial ATPase activity.
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    URL: http://dx.doi.org/10.1007/BF00743246
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  • 16
    Electronic Resource
    Electronic Resource
    Long-term efficacy of propranolol in experimental myocardial infarction (1984)
    Springer
    Bulletin of experimental biology and medicine 98 (1984), S. 915-918 
    Details
    ISSN: 1573-8221
    Keywords: myocardial infarction ; repair processes ; propranolol ; intracellular regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00806307
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  • 17
    Electronic Resource
    Electronic Resource
    Der Einfluß von Cadmium, Zink, Blei und Quecksilber auf die Enzymaktivität beiSaccharomyces cerevisiae in vitro (1983)
    Springer
    European journal of nutrition 22 (1983), S. 205-212 
    Details
    ISSN: 1436-6215
    Keywords: Schwermetallwirkung ; Malatdehydrogenase ; Glutamatdehydrogenase ; Glycerinaldehyd-3-phosphatdehydrogenase ; Saccharomyces cerevisiae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary The difference between cadmium, zinc, lead, and mercury in regard of their effects on the activity of the enzymes tested is very slight. Concentrations higher than 10−5 M reduce significantly the activity of the enzymes, and concentrations of approximately 10−3 M inhibit it completely. An increase of the activity cannot be detected. The addition of combinations of cadmium, zinc, and lead results in a summing up of the toxic effects, whereas the interaction between mercury and the other three heavy metals shows a cumulative effect, which is appointed nearly completely by the heavy metal more toxic. The findings suggest that under in-vitro conditions there exists a direct interaction between the heavy metals and the enzymes.
    Notes: Zusammenfassung Die vier Schwermetalle Cadmium, Zink, Blei und Quecksilber unterscheiden sich in ihrer Wirkung auf die Aktivität der untersuchten Enzyme nur sehr wenig. Konzentrationen über 10−5 M vermindern die Enzymaktivität signifikant, und Konzentrationen von etwa 10−3 M unterbinden sie völlig. Eine Steigerung der Enzymaktivität läßt sich nicht feststellen. Die Zugabe von Cadmium-, Zink- und Bleikombinationen führt zu einer Addition der toxischen Effekte, während bei der Interaktion zwischen Quecksilber und den anderen drei Schwermetallen die Gesamtwirkung fast ausschließlich durch das stärker hemmende Schwermetall allein bestimmt wird. Die erhaltenen Ergebnisse lassen vermuten, daß es unter Invitro-Bedingungen zu einer direkten Wechselwirkung zwischen den Schwermetallen und den Enzymen kommt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02024695
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  • 18
    Electronic Resource
    Electronic Resource
    Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 741-745 
    Details
    ISSN: 1432-1041
    Keywords: betaxolol ; salbutamol ; propranolol ; airway conductance ; beta1-selectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on specific airway conductance (sGaw) of placebo, betaxolol and propranolol following the inhalation of salbutamol were studied in 8 healthy volunteers by whole body plethysmography. Each subject received placebo and single oral doses of betaxolol 40 mg and 80 mg, and propranolol 160 mg, and 320 mg. sGaw was measured before dosing and after 2 h, just before salbutamol was inhaled. It was then measured again after 15 min and 0.5, 1, 2, 3, 4 and 6 h. sGaw 2 h after the beta-blockers did not differ from the value whilst on placebo. The peak response to salbutamol after placebo and both doses of betaxolol was almost identical, whereas it was significantly reduced after propranolol. The AUC of the response to salbutamol over 6 h showed a reduction of 11% after betaxolol and of 19% after propranolol (p〈0.01 between β-blockers). The results indicate that, after betaxolol and in contrast to propranolol, a proportion of the bronchial β2-receptor population remains available to a β2-agonist.
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    URL: http://dx.doi.org/10.1007/BF00607080
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    Felodipine — A new vasodilator, in addition to β-receptor blockade in hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
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    URL: http://dx.doi.org/10.1007/BF00542340
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  • 20
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    Chronic propranolol administration during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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    URL: http://dx.doi.org/10.1007/BF00542115
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  • 21
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    Long acting beta-blockers in the twenty fourth hour (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 717-720 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; metoprolol ; exercise tests ; moderate hypertension ; oxygen uptake ; blood glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen mild to moderate hypertensives were submitted to exercise testing using a bicycle ergometer with a fixed load. Heart rate, blood pressure and ECG were recorded throughout 5 min exercise and 10 min recovery. Oxygen uptake was measured during the final minute of exercise and blood glucose estimation and serum drug levels assessed 5 min after recovery. The above measurements were made after exactly 24 h following seven days administration of 160 mg of long acting (L.A.) propranolol, 200 mg of sustained action (S.A.) metoprolol and two matched placebos. Propranolol L.A. was superior to Metoprolol S.A. in the reduction of exercise induced tachycardia and both drugs were significantly superior to placebos. Both drugs were effective agents for the lowering of resting blood pressure after 24 h but propranolol L.A. was more effective in the lowering of systolic peaks observed during exercise. There was no significant effect upon oxygen uptake and blood glucose. The incidence of side effects was low and showed no significant difference from placebo.
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    URL: http://dx.doi.org/10.1007/BF00542508
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  • 22
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    The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 721-728 
    Details
    ISSN: 1432-1041
    Keywords: captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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    URL: http://dx.doi.org/10.1007/BF00542509
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  • 23
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    Metabolism of propranolol in the human maternal-placental-foetal unit (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 727-732 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; foetus ; placenta ; metabolism ; pregnancy ; plasma levels ; plasma protein binding ; delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean±SD) were: propranolol 0.32±0.17, propranolol glucuronide 0.86±0.36, 4-hydroxypropranolol 1.4±1.0, 4-hydroxypropranolol glucuronide 0.71±0.45 and naphthoxylactic acid 3.0±1.6. P binding in cord plasma at delivery was 67.2±3.9% (mean±SD) which was significantly less (‘t’=13.4,df=13,p〈0.001) than the P binding in maternal plasma at delivery (87.5±1.6%, mean±SD). The plasma protein binding (mean±SD) of naphthoxylactic acid in cord plasma (98.6±0.2%) was significantly greater (‘t’=3.808,df=4,p〈0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6±0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.
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    URL: http://dx.doi.org/10.1007/BF00607078
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  • 24
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    Augmented vasoconstrictor response to head-up tilt in peripheral tissues during beta-receptor blockade (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 3-7 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; vasoconstrictor response ; subcutaneous blood flow ; skeletal muscle blood flow ; head-up tilt ; baroreceptor reflex ; peripheral resistance vessels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Subcutaneous and skeletal muscle blood flow in the forearm during 30° head-up tilt was studied in 15 healthy subjects before and during treatment with propranolol. Relative blood flow was estimated by the local 133Xe washout technique. Head-up tilt elicited greater vasoconstriction in both tissues during beta-receptor blockade as compared to the pretreatment period. Proximal nerve blockade with lidocaine prevented the vasoconstrictor response in subcutaneous tissue to the tilt. In skeletal muscle injection of a low dose of propranolol had no effect on the vasoconstrictor response to tilt. Therefore, the augmented vasoconstrictor response to head-up tilt during beta-receptor blockade is most probably due to centrally elicited (baroreceptor) and neurogenically mediated impulses to resistance vessels in peripheral tissues and not to “unmasking” of peripheral alpha-receptors.
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    URL: http://dx.doi.org/10.1007/BF00544005
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  • 25
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    Family study of genetic and environmental factors determining the protein binding of propranolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 437-441 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; protein binding ; genetic factors ; environmental factors ; plasma orosomucoid ; plasma albumin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unbound fraction of propranolol was found to vary from 1.9 to 13.2% in 434 plasma samples from members of 132 families. As expected, there was a linear correlation between the ratio of bound/unbound propranolol and the orosomucoid concentration (r=0.67, P〈0.001). Albumin concentration did not influence propranolol binding. The unbound fraction was negatively correlated with obesity and alcohol intake, but was not significantly influenced by age and sex. By applying path analysis, 21% of the variability in propranolol binding could be ascribed to genetic factors and 5% to common environmental factors.
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    URL: http://dx.doi.org/10.1007/BF00542107
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    Comparative haemodynamic dose-response effects of intravenous propranolol and pindolol in patients with coronary heart disease (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 157-165 
    Details
    ISSN: 1432-1041
    Keywords: coronary heart disease ; beta-blockade ; haemodynamics ; propranolol ; pindolol ; intrinsic sympathomimetic activity ; partial agonist activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine whether the depression of left ventricular pumping activity associated with beta-blockade alone could be offset by a substantial degree of partial agonist activity, the haemodynamic dose-response effects of intravenous propranolol and pindolol were compared in a randomised between-group saline controlled study in twenty patients with angiographically proven coronary artery disease. The intravenous doses of propranolol (2–16 mg) and pindolol (0.2–1.6 mg) used were selected on the basis of published reports of equivalence in terms of exercise blockade of chronotropic beta-adrenoceptors. Following four intravenous boluses of each drug, administered according to a cumulative log-dosage schedule, there was a log-linear increase in the plasma concentrations of each drug. The range of plasma concentrations achieved were those which have been shown to be associated with substantial attenuation of sympathetic stimulation of cardiac beta-adrenoceptors. At rest propranolol resulted in dose-related linear reductions in heart rate and cardiac output and linear increases in left heart filling pressure and systemic vascular resistance compared with saline-controlled measurements. The only statistically significant change at rest after pindolol was a small increase in the left heart filling pressure. The calculated systemic vascular resistance was increased after propranolol but unchanged after pindolol. During supine bicycle exercise the systolic blood pressure increased less after propranolol than after saline or pindolol. The increments in all other measured haemodynamic variables during exercise were equally influenced by the two drugs. Propranolol resulted in a significantly greater depression of the relationship between left heart filling pressure and cardiac output at rest and during exercise than an equivalent beta-blocking dose of pindolol. The contrasting haemodynamic profile of the two drugs is explicable by the partial agonist stimulation of the heart by pindolol directly maintaining left ventricular pumping activity and simultaneously lowering afterload by stimulating vasodilator beta2-adrenoceptors in peripheral arteriolar resistance vessels. In patients with impairment of left ventricular function due to coronary heart disease who require intravenous beta-blocking therapy, partial agonist activity in a beta-blocking drug may be haemodynamically advantageous.
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    URL: http://dx.doi.org/10.1007/BF00543785
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  • 27
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    Divergent effects of atenolol, practolol and propranolol on the peripheral metabolic changes induced by dynamic exercise in healthy men (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 293-297 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; metabolic changes ; propranolol ; atenolol ; practolol ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been made of the effects of intravenous atenolol, practolol and propranolol on the changes induced by exhaustive dynamic physical exercise in blood pressure, heart rate and blood levels of lactate, glucose, insulin, free fatty acids and potassium. The mean endurance of dynamic exercise was reduced by all three beta-blockers, most markedly by propranolol. After all the beta-blockers heart rate showed a similar decrease during the first 60 min of exercise; atenolol caused the smallest reduction at exhaustion. All three beta-blockers lowered the systolic blood pressure during exercise; propranolol was the most active agent both during exercise and during recovery. The diastolic pressure was higher during exercise after treatment with the beta-blockers, especially propranolol. The beta-blockers did not markedly affect the elevation of blood glucose was abolished by atenolol. Plasma insulin was reduced by exercise after beta-blockade, most markedly after propranolol and practolol. All the beta-blockers were equipotent in reducing up to 60 min the exercise-induced increase in plasma free fatty acids, although at exhaustion propranolol had a significantly greater effect than atenolol or practolol. Serum potassium was higher after propranolol and atenolol than after practolol during exercise and recovery.
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    URL: http://dx.doi.org/10.1007/BF01037936
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  • 28
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    The antiarrhythmic effects of controlled release disopyramide phosphate and long acting propranolol in patients with ventricular arrhythmias (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 729-734 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; cardiac arrhythmias ; propranolol ; slow release formulations ; plasma levels ; 24-hour ECG monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antiarrhythmic effect of slow-release disopyramide phosphate (DR) 300 mg twice daily and of long-acting propranolol (PR) 1 × 160 mg daily was compared in a randomized cross-over study in patients with premature ventricular beats (PVB). 12 patients with PVB (Lown Classes II–V) were given: placebo I for 3 days, DR or PR for 7 days, placebo II for 5 days and PR or DR for 7 days. During each study phase Holter-ECG recordings were taken over a period of 24h. With DR 6 patients showed a positive qualitative effect, improving by at least one Lown class, whereas only 2 patients did so with PR. With DR reduction of PVB〉80% occurred in 7 patients, and with PR in 2 patients. In all patients with any reduction in PVB, the median decrease was 85% with DR and 59% with PR. The overall results suggest that the antiarrhythmic effect of disopyramide phosphate in the slow-release preparation is at least satisfactory and comparable to that of disopyramide phosphate in the standard capsule formulation given in the usual and more complicated regime of four divided doses. The antiarrhythmic effect of PR in the recommended dose as given was not convincing.
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  • 29
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    Local blood flow regulation in normotensive man during prolonged treatment with propranolol (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 723-726 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; sympathetic nerve activity ; subcutaneous blood flow ; muscle blood flow ; autoregulation ; veno-arteriolar reflex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of propranolol on blood flow in peripheral tissues was studied in 10 normotensive subjects. Adequacy of beta-blockade was ascertained by an ergometric test. Perfusion of the subcutaneous tissue and skeletal muscle was measured by the local133Xe-washout technique. The arteriolar dilatation underlying the autoregulatory response to a decrease in arterial perfusion pressurehead was not affected by beta-blockade. Propranolol did not change the magnitude of arteriolar constriction elicited by the local sympathetic veno-arteriolar reflex. Thus, the locally induced increase in the discharge rate along the peripheral sympathetic adrenergic fibres did not lead to measurable change in beta-receptor activity. The present results indicate that local bloodflow regulatory mechanisms are not affected by propranolol. They also indicate that the direct peripheral effects of propranolol are of no clinical importance in normotensive subjects in the supine position, when the general activity in the sympathetic nervous system is low.
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    Effect of atenolol and propranolol on the systemic and regional hemodynamics (1983)
    Springer
    Bulletin of experimental biology and medicine 96 (1983), S. 949-951 
    Details
    ISSN: 1573-8221
    Keywords: atenolol ; propranolol ; hemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00833046
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    Dependence of the cardiovascular effects of pindolol on the individual sympathetic nervous activity (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 383-387 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; propranolol ; beta-adrenergic activity ; beta-adrenergic sensitivity ; beta-blocking agents ; intrinsic sympathomimetic action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To investigate the mechanism of the relative beta-antagonist and agonist properties of pindolol, the cardiovascular effects of i.v. pindolol 0.01 mg/kg were studied in 23 subjects with different baseline levels of cardiac beta-adrenergic function. Baseline cardiac beta-adrenergic activity was assessed by the decrease in heart rate following intravenous propranolol 0.2 mg/kg (ΔHRβ) after parasympathetic blockade with intravenous atropine 0.04 mg/kg. Cardiac beta-adrenergic sensitivity was defined by the positive chronotropic effect of a three minute infusion of isoprenaline 0.005 µg/kg/min. The chronotropic effect of intravenous pindolol was negatively correlated with resting beta-adrenergic activity (R=−0.81, p〈0.001). The traditional point of ΔHRβ, at which pindolol shifted from beta-antagonist to beta-agonist action, was 17 beats/min, i.e. pindolol decreased heart rate in subjects with ΔHRβ greater than 17 bpm, and increased heart rate in those with ΔHRβ less than 17 bpm. The chronotropic effect of intravenous pindolol, however, was positively correlated with beta-sensitivity (R=+0.73, p〈0.001). Thus subjects with the greatest increment in heart rate with isoprenaline had an increased heart rate with pindolol, while those with the lowest increment in heart rate with isoprenaline had a decreased heart rate with pindolol. Intravenous pindolol decreased cardiac index and increased total peripheral resistance in the group with ΔHRβ more than 17 bpm, and it had the contrary actions in the group with ΔHRβ less than 17 bpm. Blood pressure in both groups was not significantly changed by pindolol. Compared to endogenous catecholamines, pindolol was considered to possess higher beta-adrenocepter affinity and weaker beta-adrenoceptor stimulating action. Therefore, pindolol produced a net beta-blocking action in subjects with elevated cardiovascular sympathetic nervous activity and beta-stimulating action in subjects with reduced sympathetic nervous activity.
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    Clinical pharmacology of a new β-adrenoceptor blocking drug, befunolol (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 189-195 
    Details
    ISSN: 1432-1041
    Keywords: befunolol ; propranolol ; pharmacokinetics ; pharmacodynamic effects ; beta-adrenoceptor blocking agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
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  • 33
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    Response of blood pressure and plasma norepinephrine to propranolol, metoprolol and clonidine during isometric and dynamic excercise in hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 275-279 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; hypertension ; clonidine ; plasma catecholamines ; metoprolol ; propranolol ; blood pressure responses ; isometric work ; dynamic work
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of metropolol (beta1-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.
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    Pharmacokinetics of bendroflumethiazide alone and in combination with propranolol and hydralazine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    Details
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
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    Binding ofβ-adrenoceptor blocking drugs to human serum albumin, to α1-acid glycoprotein and to human serum (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 253-256 
    Details
    ISSN: 1432-1041
    Keywords: beta-blocker ; rheumatoid arthritis ; protein-binding ; alpha1-acid glycoprotein ; oxprenolol ; propranolol ; alprenolol ; pindolol ; timolol ; atenolol ; metoprolol ; sotalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The binding of 8 β-adrenergic blocking drugs to human serum albumin, to α1-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to α1-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum α1-glycoprotein concentration and the percentage binding.
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    Prediction of bioavailability for drugs with a high first-pass effect using oral clearance data (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 85-90 
    Details
    ISSN: 1432-1041
    Keywords: lignocaine ; verapamil ; propranolol ; bioavailability ; predictions ; first pass effect ; oral clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary For drugs with a high hepatic clearance, bioavailability is low due to the so-called “first pass effect”. Prediction of the bioavailability for these drugs has been only lossely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.
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    Long-term therapy of arterial hypertension with nifedipine given alone or in combination with a beta-adrenoceptor blocking agent (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 101-103 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; long-term treatment ; adverse effects ; propranolol ; timolol ; metoprolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine during long-term therapy was investigated in 5 patients receiving nifedipine as the sole drug and in 10 patients who had nifedipine in combination with a beta-adrenoceptor blocking drug. Nifedipine monotherapy was problematic because of side-effects and development of resistance to therapy after a few months. In patients who received the combined therapy significant and stable blood pressure reductions were maintained during the whole observation period (12–33 months). However, the occurrence of peripheral oedema in 4 of the patients necessitated the addition of a thiazide diuretic. It is concluded that nifedipine is not a first choice drug for the long-term treatment of arterial hypertension. When given in addition to a beta-blocker it is well tolerated and powerful but fluid retention may occur and if not counteracted by a diuretic it will limit the antihypertensive potential of the drug.
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    Variability of beta-blocker pharmacokinetics in young volunteers (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 37-42 
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    ISSN: 1432-1041
    Keywords: metoprolol ; propranolol ; oxprenolol ; pharmacokinetics ; acetubolol ; diacetolol ; oral contraceptive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young healthy volunteers. In order to assess the inter-and intra-subject variability the following pharmacokinetic parameters were compared: AUC o 24 , Cmax, tmax and t1/2. The smallest variation in inter-subject variability was seen with oxprenolol and acebutolol: intrasubject variability was more uniform. Female volunteers taking an oral contraceptive generally had higher AUC o 24 and Cmax values than those not. This finding reached statistical significance only for metoprolol AUC o 24 .
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    Comparative effects of alinidine and propranolol in ischaemic heart disease (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 389-396 
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    ISSN: 1432-1041
    Keywords: alinidine ; propranolol ; ischaemic heart disease ; maximal exercise test ; heart-rate ; blood pressure ; ECG change ; effect duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of single oral doses of alinidine 40 mg, propranolol 40 mg or placebo during a maximal exercise test on a bicycle ergometer in patients with angina pectoris were studied in a randomised, double blind study. 2 and 5 h after drug intake a small fall in resting heart rate and systolic blood pressure was observed both after alinidine and propranolol. At a fixed work load both drugs decreased heart rate, systolic blood pressure, double product and the extent of ST segment depression. Total work performed and time to appearance of angina pectoris were increased 2 h alinidine and propranolol. The same effects were still apparent 5 h after propranolol but not after alinidine. At peak exercise neither drug had any effect on the extent of ischaemic ST segment depression.
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  • 40
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    Effects of acute and long-term beta-adrenoceptor blockade with propranolol on haemodynamics, plasma catecholamines and renin in essential hypertension (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 377-382 
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    ISSN: 1432-1041
    Keywords: propranolol ; essential hypertension ; acute and chronic treatment ; haemodynamic effects ; plasma renin ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an acute intravenous and repeated oral doses of propranolol on haemodynamics, plasma and urinary catecholamines and plasma renin activity was studied in patients with essential hypertension. Intravenous injection of propranolol 5 mg produced a fall in cardiac output but had no consistent effect on blood pressure. Treatment with oral propranolol for 24 weeks lowered cardiac output and blood pressure; total peripheral resistance did not differ from the pretreatment values. Neither acute intravenous nor chronic oral administration of the beta-blocker affected the resting plasma levels of noradrenaline and adrenaline. Long-term treatment with propranolol reduced urinary excretion of vanilmandelic acid without affecting urinary catecholamine excretion. Acute intravenous injection of propranolol decreased plasma renin activity less than did chronic oral treatment with the drug. The observed time course of plasma renin activity was compatible with the view that suppression of this enzyme contributed to the antihypertensive effect of propranolol.
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    Influence of hyperthyroidism on the kinetics of methimazole, propranolol, metoprolol and atenolol (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 379-384 
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    ISSN: 1432-1041
    Keywords: hyperthyroidism ; propranolol ; methimazole ; metoprolol ; atenolol ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic profiles of oral methimazole 40mg, propranolol 80mg, metoprolol 100mg and atenolol 100mg were compared in hyperthyroid patients both during the hyper-and euthyroid states. For methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p〈0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.
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    Comparison of labetalol, propranolol and hydralazine in hypertensive out-patients (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 457-460 
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    ISSN: 1432-1041
    Keywords: hypertension ; propranolol ; hydralazine ; labetalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.
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    Pharmacokinetics of propranolol and sotalol in hyperthyroidism (1982)
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    European journal of clinical pharmacology 21 (1982), S. 373-377 
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    ISSN: 1432-1041
    Keywords: propranolol ; sotalol ; thyrotoxicosis ; bioavailability ; serum tri-iodothyronine ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination and bioavailability of two beta-blocking agents, propranolol and sotalol, were studied in 10 thyrotoxic patients, both before and after treatment with iodine-131. Each subject received in random order propranolol 160 mg and sotalol 160mg as single oral doses both while hyperthyroid and after euthyroidism had been achieved. The pharmacokinetics of sotalol was not affected by hyperthyroidism, whereas serum propranolol concentrations were significantly lower during hyperthyroidism than in the euthyroid state. During hyperthyroidism, the bioavailability of propranolol was significantly reduced (p〈0.05) and its clearance was increased (p〈0.005), whereas there was no difference in its serum t1/2. This indicates that the bioavailability of propranolol in hyperthyroidism is reduced by a mechanism which may depend on increased first-pass metabolism in the liver, or on an increased distribution volume of the drug. Both propranolol and sotalol caused a slight decrease in serum tri-iodothyronine concentration. As the effects of beta-blocking agents on the symptoms of hyperthyroidism are correlated with the serum concentration of the drugs, sotalol, with its long half-life and unaltered elimination in hyperthyroidism, has certain advantages over propranolol in the treatment of thyrotoxicosis.
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    The use of long-acting propranolol (‘Inderal’ LA) in the management of elderly hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 379-381 
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    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; elderly patients ; long-acting propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of ‘Inderal’ LA1 (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with ‘Inderal’ LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with ‘Inderal’ LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after ‘Inderal’ LA than following the intake of conventional propranolol (p〈0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. ‘Inderal’ LA was well tolerated and side effects were minimal.
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    Lowering the concentration of high-affinity binding sites for calcium ions in rat heart sarcolemmal membranes by the beta-blocker propranolol (1982)
    Springer
    Bulletin of experimental biology and medicine 93 (1982), S. 631-634 
    Details
    ISSN: 1573-8221
    Keywords: propranolol ; sarcolemma ; myocardium ; glucocorticoids ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00830779
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    The reconstitution of oxidative phosphorylation in mitochondria isolated from a ubiquinone-deficient mutant ofSaccharomyces cerevisiae (1982)
    Springer
    Journal of bioenergetics and biomembranes 14 (1982), S. 159-169 
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    ISSN: 1573-6881
    Keywords: Respiratory chain ; ATP synthesis ; mitochondria ; ubiquinone ; Saccharomyces cerevisiae ; cytochrome oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Mitochondria, isolated from the ubiquinone-deficient nuclear mutant ofSaccharomyces cerevisiae E3-24, are practically unable to oxidize exogenous substrates. Respiratory activity, coupled to ATP synthesis, can, however, be reconstituted by the simple addition of ethanolic solutions of ubiquinones. A minimal length of the isoprenoid side chain (≥3) was required for the restoration. Saturation of the reconstitution required a large amount of exogeneous ubiquinone, in excess over the normal content present in the mitochondria of the wild type strain. A similar pattern of reconstituted activities could be also obtained using sonicated inverted particles. Mitochondria and sonicated particles are also able to carry out a dye-mediated electron flow coupled to ATP synthesis in the absence of added ubiquinone, using ascorbate or succinate as electron donor. This demonstrates that the energy conserving mechanism at the third coupling site of the respiratory chain is fully independent of the presence of the large mobile pool of ubiquinone in the membrane.
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  • 47
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    Dissociation between duration of plasma catecholamine and blood pressure responses to beta-adrenergic blockade in normotensive subjects during physical exercise (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 83-88 
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    ISSN: 1432-1041
    Keywords: propranolol ; noradrenaline ; normotension ; withdrawal ; exercise ; effect duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of acute and chronic treatment with the adrenergic beta-receptor blocking agent propranolol (P) on blood pressure (BP), heart rate (HR) and plasma catecholamine concentration (CA) was studied in 7 normotensive healthy volunteers, and in 5 normotensive patients with cardiac neurosis, at rest, during physical exercise and after sudden withdrawal of the drug. The first oral dose of P 120 mg as well as chronic treatment (3×80 mg/day for 3 months) caused a significant reduction in HR and supine BP. Resting values of CA were not changed. After sudden withdrawal of the long-term therapy with P, supine BP and HR returned to normal, and again, resting levels of CA remained unchanged. A physical exercise test, performed 2 1/2 days after withdrawal of the betablocker, was not indicative of a transient sympathetic hyper-response. Striking effects of the drug on CA were observed during acute and chronic treatment with P when physical exercise was performed (bicycle ergometer, 150 W). Exercise values of CA were about twice as high during P treatment as without the drug, when the exercise test was performed 2 h after the first oral dose. At the same time, however, exercise BP and HR were significantly reduced. Similar reactions during the exercise test were also seen during chronic treatment with P, when the test was performed 2 hours after the last dose of the drug. But, when the exercise test was undertaken during chronic treatment 8 h after drug intake, the drug effect on CA had disappeared, whereas the effects on BP and HR still were present. The dissociation during chronic treatment between the effect on the duration of plasma CA and that of the pharmacodynamic responses to beta-adrenergic blockade with P is the principal finding of the study. A hypothesis is offered for interpretation of the observations. The time interval between measurement of drug effect and drug intake must be carefully observed in assessing different or controversial drug responses.
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    Pharmacokinetics and pharmacodynamics of propranolol stereoisomers in hyperthyroid patients (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 197-203 
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    ISSN: 1432-1041
    Keywords: propranolol ; hyperthyroidism ; stereoisomers ; radioimmunoassay ; beta-receptor sensitivity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of propranolol stereoisomers after administration of a single oral dose of the racemic drug was investigated in seven hyperthyroid patients before and after antithyroid drug therapy. The possibility of hypersensitivity to propranolol in the patients was evaluated by constructing plasma propranolol concentration — beta-blocking effect curves. There was no statistically significant difference in elimination half-life (t1/2) between (±)- and (−)-propranolol before and after antithyroid drug therapy. However, the plasma clearance ( $$\dot V_p $$ ) of (−)-propranolol was smaller than that of (±)-propranolol, and the difference was statistically significant after antithyroid drug therapy. Decreased $$\dot V_p $$ was observed in 3 aged hyperthyroid patients compared to the value after antithyroid drug therapy. $$\dot V_p $$ decreased or did not change in young patients after therapy. No significant difference was observed in the relationship between the tilt-induced pulse rate response and plasma propranolol concentration when treated patients became euthyroid compared to their response in the hyperthyroid state.
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    Plasma propranolol steady state concentrations in thyroid disorders (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 329-333 
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    ISSN: 1432-1041
    Keywords: propranolol ; hyperthyroidism ; hypothyroidism ; plasma level ; steady state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma propranolol steady-state concentrations (Css) were measured in 24 hyperthyroid and 6 hypothyroid patients before and after correction of the thyroid disorder. Following treatment of hyperthyroidism by surgery, antithyroid drugs or radioiodine, there was a significant rise in the plasma propranolol Css in patients receiving propranolol either 160 mg/day, 240 mg/day, or 480 mg/day. In addition, in five patients the area under the plasma propranolol concentration versus time curve during a dosing interval increased significantly from 405 ng/ml/h when hyperthyroid to 778 ng/ml/h when euthyroid. In the hypothyroid patients given propranolol 160 mg/day concomitantly with 1-thyroxine therapy the plasma propranolol Css fell significantly when euthyroid. There was a small but significant increase in the degree of plasma protein binding of propranolol, following treatment of hyperthyroidism and a significant decrease following correction of hypothyroidism. It is concluded that thyroid disorders markedly influence propranolol handling.
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    Lack of adrenergic influence on renin release after furosemide in normal man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 339-342 
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    ISSN: 1432-1041
    Keywords: furosemide ; propranolol ; sympathetic nervous system ; plasma renin concentration ; plasma catecholamines ; renin release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of the sympathetic nervous system in furosemide-induced renin release was investigated in six normal subjects. After intravenous administration of furosemide, plasma renin concentrations increased more than two-fold within 15 min. Neither replacement of urinary fluid loss by intravenous infusion of saline nor pharmacological betablockade with d,1-propranolol changed the renin response to furosemide. The activity of the sympathetic nervous system, as estimated by measurement of plasma catecholamine concentrations, remained at the reference level after furosemide. It is concluded that the sympathetic nervous system is not involved in renin release after intravenous administration of furosemide.
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    The effect on plasma prolactin, growth hormone and luteinising hormone concentrations of single oral doses of propranolol and tolamolol in normal man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 103-108 
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    ISSN: 1432-1041
    Keywords: tolamolol ; propranolol ; prolactin ; beta-blockade ; growth hormone ; luteinising hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a placebo controlled double-blind study in six healthy male volunteers the effects of single oral doses of 100 mg and 200 mg of tolamolol on plasma concentrations of prolactin, growth hormone and luteinising hormone were investigated. In a second placebo controlled single-blind study in a further six healthy male volunteers the effects of single oral doses of 200 mg tolamolol and 160 mg propranolol on the same plasma hormone concentrations were compared. A dose dependent increase in plasma prolactin concentration was demonstrated after tolamolol. The increase in plasma prolactin concentration was not evident after propranolol. Plasma growth hormone and luteinising hormone concentrations were not significantly changed by either propranolol or tolamolol.
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    Cardioselectivity of atenolol in asthmatic patients (1981)
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    European journal of clinical pharmacology 21 (1981), S. 173-176 
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    ISSN: 1432-1041
    Keywords: atenolol ; propranolol ; asthma ; isoprenaline ; FEV1 ; heart rate ; cardioselectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This double-blind, randomised, within patient, placebo-controlled study set out to investigate the effect of a cardioselective beta-blocker, atenolol, at different oral doses (50, 100 and 200 mg) and a non-selective agent, propranolol (40 mg), upon 1. airways resistance (forced expiratory volume at one second=FEV1) and 2. the bronchodilator action of increasing doses of inhaled isoprenaline, in patients with co-existent hypertension and reversible airways obstruction. In 10 patients, two hours after drug administration, the 3 doses of atenolol caused a significantly greater (P〈0.05) degree of B1-blockade than propranolol. In contrast the 3 doses of atenolol caused significantly less (P〈0.05 to 0.01) B2-blockade as evidenced by a smaller fall in FEV1. The isoprenaline FEV1 dose response curves were displaced progressively to the right of the placebo curve with increasing doses of atenolol, but the greatest displacement was with propranolol. It was concluded that patients with reversible airways obstruction who require beta-blockade should be given a low dose of a cardioselective agent in conjunction with, if required, a beta2 stimulant such as isoprenaline. Such a treatment will be less likely to cause a troublesome increase in airways resistance and the bronchodilator action of the beta2 stimulant will be almost fully preserved.
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    A comparison between propranolol, practolol and betaxolol (SL75212) on the circulatory and metabolic responses to insulin-induced hypoglycaemia (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 177-184 
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    ISSN: 1432-1041
    Keywords: propranolol ; practolol ; betaxolol ; hypoglycaemia ; free fatty acids ; glycerol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Six healthy male volunteers received equivalent intravenous beta-blocking doses of propranolol, practolol and betaxolol (SL75212) or saline at weekly intervals Sixty minutes later 0.1 unit/kg insulin was given intravenously. 2. In all studies, maximum hypoglycaemia (mean 1.2 mmol/l) was reached thirty minutes after insulin. Recovery from hypoglycaemia was delayed with propranolol but practolol and betaxolol had no effect. 3. Propranolol blocked the tachycardia and widening of pulse pressure seen in saline treated subjects. It also blocked the rebound rise in free fatty acids (FFA) and glycerol concentrations that followed the nadir of hypoglycaemia. 4. Neither practolol nor betaxolol had significant effects on pulse rate or blood pressure but betaxolol resembled propranolol in blocking the rebound rise in FFA and glycerol, while practolol blocked the rise in glycerol alone. 5. The magnitude of the rise in growth hormone following hypoglycaemia was similar in all groups, but the peak was earlier after practolol and betaxolol.
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    Correlation between propranolol in plasma and urine, renin-aldosterone system and blood pressure in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 251-258 
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    ISSN: 1432-1041
    Keywords: aldosterone ; hypertension ; propranolol ; blood pressure ; plasma level ; renin ; urine level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg×4 (Group 1), 80 mg×4 (Group 2) and 160 mg×4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA and PAC fell in all groups, and remained reduced during C and D in Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin-aldosterone system was initially suppressed in all groups, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00618774
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    Mitotic activity of the regenerating rat liver during stimulation of α- and β-adrenoreceptors (1981)
    Springer
    Bulletin of experimental biology and medicine 91 (1981), S. 375-377 
    Details
    ISSN: 1573-8221
    Keywords: regeneration of the liver ; propranolol ; mitotic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00839380
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  • 56
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    Comparison of the effects of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 135-139 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561580
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  • 57
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    Comparison of the activity and plasma levels of oxprenolol, slow release oxprenolol, long acting propranolol and sotalol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 419-424 
    Details
    ISSN: 1432-1041
    Keywords: oxprenolol ; propranolol ; sotalol ; slow release preparation ; plasma level ; exercise tachycardia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Observations were made in 5 healthy subjects who exercised before and 1, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg long acting propranolol and 400 mg sotalol. Blood samples were obtained before and at 1, 2, 3, 6, 8, 10 and 24 h after drug administration and assayed for drug concentration. Although the plasma concentration of oxprenolol after S. R. oxprenolol was significantly less at 1 and 2 h and significantly greater at 24 h than after conventional oxprenolol, there was little difference between the effects of the two drugs on an exercise tachycardia. The plasma level of propranolol and the reduction in an exercise tachycardia after L. A. propranolol increased slowly to reach a peak at 6 h and then declined gradually to 24 h. The maximum plasma concentration and effect after sotalol occurred at 3 h and then declined with an elimination half-life of 12.1 h. At 24 h the percentage reduction in an exercise tachycardia was 8.3±2.5 after oxprenolol, 10.0±2.3 after S. R. oxprenolol, 18.0±3.2 after L. A. propranolol and 14.7±3.4% after sotalol.
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    URL: http://dx.doi.org/10.1007/BF00570158
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  • 58
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    Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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    URL: http://dx.doi.org/10.1007/BF00636790
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  • 59
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    Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 315-320 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; metoprolol ; hyperthyroidism ; plasma level ; thyroid hormones ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects and plasma concentrations of different doses of propranolol and metoprolol were studied in 34 hyperthyroid patients. The initial daily doses were propranolol 160 mg or metoprolol 200 mg. If the resting heart rate remained above 75 beats per min after treatment for 4–7 days, the dose was increased and the patient re-examined after a further 4–7 days. Propranolol (n=17) caused a reduced heart rate, a decrease in serum 3,3′,5-triiodothyronine (T3) and an increase in serum 3,3′,5′-triiodothyronine (reverse T3, rT3). In 10 patients, there was no change in T3 or rT3 until the daily dose of propranolol had been increased to 240 or 320 mg. The plasma level of propranolol was significantly correlated with the decrease in T3 and the increase in rT3. Metoprolol (n=17) caused a reduction in heart rate similar to that following propranolol. However, serum T3 was only slightly reduced even after an increase in dose to 300 or 400 mg, and serum rT3 was not altered. Metoprolol concentrations were not significantly correlated with the fall in T3. It appears that the influence ofβ-blockers on T4 conversion is of little importance for the clinical improvement in hyperthyroid patients, and rather it is a consequence ofβ 1-adrenergic blockade interfering with the effect of T3. In addition, the findings support the assumption that therapeutic failure withβ-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561388
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  • 60
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    Evaluation of a radioreceptor assay for beta-adrenoceptor antagonists in plasma (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 349-354 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; radioreceptor assay ; beta-adrenoceptor antagonists ; lung membranes ; plasma level ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A radioreceptor assay (RRA) recently developed in this laboratory for beta-adrenoceptor antagonists in plasma was evaluated in normal volunteers and compared with a radioimmunoassay (RIA) for propranolol. The RRA depends upon the ability of beta-adrenoceptor antagonists to compete with a radiolabelled ligand for beta-adrenoceptor binding sites on lung membranes. Unlike other assays, it measures biologically active drugs including active metabolites of the parent compound. In volunteers given a single oral dose of (±)-propranolol, considerable differences between the two assay methods were demonstrated. In other experiments this difference was shown to relate to the RIA's sensitivity to the inactive (+)-isomer of propranolol and possibly to inactive metabolites. The facility of the RRA in measuring plasma levels of several other non-selective beta-adrenoceptor antagonists was also demonstrated. By employing (−)-propranolol as the standard in the RRA, all of these drugs can be directly compared with a single and relatively simple assay technique.
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    URL: http://dx.doi.org/10.1007/BF00558447
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  • 61
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    Single daily dose penbutolol in the treatment of hypertension: A double blind crossover comparison with propranolol (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 409-413 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; hypertension ; propranolol ; double-blind crossover comparison ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penbutolol is a potent long-acting non-cardioselective beta-adrenergic blocker with partial agonist activity. A double-blind cross-over comparison of penbutolol given in a single daily dose and propranolol given twice daily in the treatment of ambulant patients with moderate hypertension is described. Fourteen patients completed the study and were treated with each drug for 12 weeks. Penbutolol in daily doses of 20–120 mg and propranolol in daily doses of 80–400 mg produced similar significant reductions in both supine and erect blood pressure. Penbutolol did not reduce heart rate to the same extent as propranolol, in equivalent doses. Penbutolol appears to produce adequate control of moderate hypertension when administered once a day, and this effect appears to be equivalent to divided doses of propranolol. No serious adverse effects were reported, although one patient receiving penbutolol experienced severe eye pains at a dose of 40 mg which resolved on crossing over to treatment with propranolol.
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    URL: http://dx.doi.org/10.1007/BF00570156
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  • 62
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    Influence of propranolol and pindolol on the haemodynamic effects of papaverine, isoprenaline and noradrenaline in hypertensive patients (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 141-146 
    Details
    ISSN: 1432-1041
    Keywords: papaverine ; propranolol ; pindolol ; hypertension ; isoprenaline ; haemodynamic effects ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of two β-adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p〈0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p〈0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the β-blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both β-blockers. While the β-blockers inhibited the β-adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the α-adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the α-and β-adrenoceptor effects of noradrenaline.
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    URL: http://dx.doi.org/10.1007/BF00561581
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  • 63
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    Comparative in vitro effects and in vivo kinetics of antithyroid drugs (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 295-299 
    Details
    ISSN: 1432-1041
    Keywords: propylthiouraci ; propranolol ; carbimazole ; methimazole ; comparative activity ; pharmacokinetics ; bioactivation ; thyroid peroxidase inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.
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    URL: http://dx.doi.org/10.1007/BF00625803
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  • 64
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    Propranolol and blood glucose: Simultaneous measurements over a wide range of doses and the effect of propranolol on the glucose tolerance test (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 415-418 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; glucose ; schizophrenia ; glucose tolerance test ; blood glucose ; plasma propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary No correlation was found between blood glucose and simultaneous measurements of plasma propranolol concentration in patients with schizophrenia, on a daily dose of 80 mg to 1800 mg of propranolol as an adjunct to phenothiazine medication. The Glucose Tolerance Test (GTT) in ten patients on propranolol and phenothiazines did not differ significantly from those of a matched control group on phenothiazine alone. Two patients with mild diabetes showed no significant change in their GTT after stopping propranolol. These observations accord with the view that relatively high doses of propranolol as an adjunct to phenothiazine medication in schizophrenia are safe from the standpoint of glucose metabolism. This does not apply to the insulin dependent diabetic who is in danger of severe hypoglycaemia when glycogenolysis is blocked by propranolol.
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    URL: http://dx.doi.org/10.1007/BF00570157
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  • 65
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    Effect of nonachlazine and oxyfedrine on central regulation of vasomotor tone (1980)
    Springer
    Bulletin of experimental biology and medicine 90 (1980), S. 914-918 
    Details
    ISSN: 1573-8221
    Keywords: vasomotor reflexes ; sympathetic activity ; nonachlazine ; oxyfedrine ; reserpine ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00833257
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