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  • 1
    Electronic Resource
    Electronic Resource
    β-Blockers and psychometric performance: Studies in normal volunteers (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 35-38 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; benzodiazepines ; nadolol ; propranolol ; psychomotor tests ; β-adrenoceptor antagonists ; lipophilicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tests of psychometric function were performed in young, normal volunteers taking several β-adrenoceptor antagonists. With single doses of atenolol, a cardioselective hydrophilic β-blocker, dosedependent effects were apparent and were maximal at a dose of 200 mg. The lipophilic non-selective β-blocker, propranolol, also produced significant impairment of psychomotor tests but these were inversely related to dose, the longest effects being at a dose of 40 mg but with little effect at 320 mg. Subsequently, a multisubject comparison of propranolol and atenolol confirmed these findings and showed the effects to be of the same order of magnitude as those produced by diazepam. Chronic administration of atenolol 100 mg, nadolol 80 mg and diazepam 5 mg daily for seven days showed some effects with all drugs during the test period; however, these were sporadic rather than persistent. Overall, β-Blockers do appear to have central effects in man which can be demonstrated by psychomotor tests. However, the relevance of these central effects to maintenance therapy and skilled performance is unclear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543708
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    The effects of chronic dosing on the β1 and β2-adrenoceptor antagonism of betaxolol and atenolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 467-471 
    Details
    ISSN: 1432-1041
    Keywords: Betaxolol ; atenolol ; nadolol ; cardioselectivity ; β-adrenocepter antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A100); and nadolol 40 mg (N40). Measurements of β1-adrenoceptorblockade (reduction of exercise heart rate) and of β2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4). Thus, despite drug accumulation after chronic-dosing, there was no evidence of any increase in either β1 or β2-adrenoceptor antagonism at steady-state in comparison with after single-dosing. The apparent dissociation between plasma concentration and β-adrenoceptor antagonism after chronic-dosing my be a consequence of β-adrenoceptor up-regulation, resulting in partial attenuation of β-blockade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315224
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  • 4
    Electronic Resource
    Electronic Resource
    Evaluation of the metabolic responses to inhaled salbutamol in the measurement of beta2-adrenoceptor blockade (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 297-300 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; salbutamol ; beta-adrenoceptor antagonists ; cardioselectivity ; metabolic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the present study was to evaluate whether metabolic responses to inhaled salbutamol may be used to measure the cardioselectivity of beta-adrenoceptor antagonists. We therefore studied the effects of oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40), and placebo (Pl) on the hypokalaemic (K) and hyperglycaemic (Glu) responses to inhaled salbutamol in five healthy subjects. Increasing doses of atenolol were associated with a progressive attenuation of ΔK compared with placebo: −0.72 mmol·l−1 (Pl) vs −0.20 mmol·l−1 (A200). However, ΔK with A200 was significantly different from the response with P40: +0.12 mmol·l−1. There were partial reductions in the hyperglycaemic response with the beta-adrenoceptor antagonists, although this was only significant (compared with Pl) for P40: ΔGlu 1.92 mmol·l−1 (Pl) vs 0.76 mmol·l−1 (P40). These results show that beta2-adrenoceptor blockade by atenolol is a dose-dependent phenomenon, which may be measured by the attenuation of salbutamol-induced hypokalaemia. However, beta2-adrenoceptor blockade by atenolol 200 mg was less than that by propranolol 40 mg. The glucose response to salbutamol was only partially blocked by propranolol and may therefore not be suitable to assess beta2-adrenoceptor antagonism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00679788
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  • 5
    Electronic Resource
    Electronic Resource
    A dose-ranging study to evaluate the β1-adrenoceptor selectivity of bisoprolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 135-139 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; bisoprolol ; β-adrenoceptor ; cardioselectivity ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose-ranging study was performed to compare the β1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. β2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mm Hg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mm Hg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess β1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of β1 and β2-adrenoceptors, and therefore possess equal degrees of β1-adrenoceptor selectivity. Increasing doses of bisoprolol and atenolol were associated with partial loss of selective β1-adrenoceptor blockade, although antagonism of β2-adrenoceptors was significantly less compared with the effects of nadolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280067
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