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  • 1990-1994  (3)
  • beta-adrenoceptor  (2)
  • atenolol  (1)
  • 1
    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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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Comparison of the efficacy and systemic effects of 4 mg and 8 mg formulations of salbutamol controlled release in patients with asthma (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 281-285 
    Details
    ISSN: 1432-1041
    Keywords: salbutamol ; asthma ; beta-adrenoceptor ; controlled release formulation ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of the present study was to compare the efficacy and systemic effects of 4 mg and 8 mg doses of salbutamol controlled release (SCR) after single dosing and at steady state in patients with asthma. Fifteen asthmatic patients (Age 36 y, FEV1 85% predicted) were given SCR 4 mg and 8 mg twice daily for 7 days in a randomised double-blind cross-over design, with at least 7 days washout between treatments. There were no differences between the bronchodilator effects of 4 mg and 8 mg doses. There was no evidence of tolerance to the bronchodilator effects after chronic dosing. Morning and evening PEFR measurements also showed improvements during treatment with SCR 4 mg and SCR 8 mg, although there were no differences between the two formulations. Both doses of SCR caused significant objective tremor responses which were maintained after chronic dosing. The 8 mg dose produced a larger tremor response after single dosing, but not at steady-state. Subjective tremor occurred in 7 patients with SCR 8 mg, and in 2 patients with SCR 4 mg. There were no cardiac arrhythmias on Holter ECG monitoring. These results suggest that the 8 mg dose of SCR was no more effective than the 4 mg formulation, and was associated with more systemic adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315111
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Comparison of hypokalaemic, electrocardiographic and haemodynamic responses to inhaled isoprenaline and salbutamol in young and elderly subjects (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 255-260 
    Details
    ISSN: 1432-1041
    Keywords: Salbutamol isoprenaline ; beta-adrenoceptor ; electrocardiogram ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of the study was to compare beta-adrenoceptor responsiveness to salbutamol (beta-2 selective agonist) and isoprenaline (non-selective) in young (n=10, age 23 y) and elderly (n=7, age 71 y) subjects. Subjects were given cumulative doubling doses of inhaled isoprenaline or salbutamol (500–4000 μg), and placebo, in a single-blind randomised cross-over design. Plasma potassium, electrocardiographic (R-R, T-wave, Q-Tc) and blood pressure responses were measured at baseline and at each dose step. There were no difference between baseline values for each of the three study days within each group of subjects. Hypokalaemia was significantly greater in response to salbutamol compared with isoprenaline in both the young (as change from baseline): −0.61 versus −0.10 mmol·1−1; and in the elderly: −0.68 versus −0.20 mmol·1−1. There were no differences between young and elderly responses. T-wave amplitude fell significantly in repsonse to isoprenaline and salbutamol, although this effect was progressively attenuated with increasing doses of isoprenaline. Maximum T-wave response (change from baseline) was greater with salbutamol than isoprenaline in the young: −0.22 versus −0.11 mV; and in the elderly: −0.17 versus −0.08 mV, and there were no differences between the two groups. There were no differences between the effects of isoprenaline and salbutamol on Q-Tc prolongation or heart rate. Chronotropic responses to salbutamol were greater in the elderly: 39 versus 24 beats·min−1. There were larger increases in SBP with isoprenaline in both groups. Falls in DBP in response to isoprenaline and salbutamol were significantly greater in the elderly. These findings suggest that inhaled isoprenaline is a less potent stimulant of extrapulmonary beta-2 adrenoceptors compared with salbutamol, but has a greater effect on cardiac beta-1 adrenoceptors. There was no evidence of a decline with ageing in the function of beta-1 or beta-2 adrenoceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315205
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    Paper (German National Licenses)
    Fulltext
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