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  • 1
    ISSN: 1432-1041
    Keywords: methoxamine ; alpha-methyl-noradrenaline ; propranolol ; baroreceptor function ; Valsalva's Manoeuvre
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Methoxamine and α-methyl-noradrenaline were administered to six healthy male subjects on separate days as rapid bolus injections until blood pressure increased by approximately 30 mmHg; Valsalva's Manoeuvre was carried out on each occasion. Propranolol (80 mg) or placebo was administered (random order, double-blind, weekly intervals) and the observations were repeated after 2 h. Baroreceptor sensitivity (ΔR-R interval ms/mmHg systolic BP) was less (p〈0.05) with α-methyl-noradrenaline than methoxamine. Propranolol abolished the differences in baroreceptor-mediated bradycardia following α-methyl-noradrenaline and methoxamine, and shifted the baroreceptor sensitivity regression lines (p〈0.05) to the left. During the release phase of Valsalva's Manoeuvre baroreceptor sensitivity was increased following propranolol. The smaller baroreceptor-mediated bradycardia response observed with α-methyl-noradrenaline does not support the hypothesis that pre-synaptic α-adrenoceptors have a physiological role in the modulation of baroreceptor function in man, and may be due to α-methyl-noradrenaline having β1-agonist activity.
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  • 2
    ISSN: 1432-1041
    Keywords: cicloprolol ; pharmacodynamics ; cardioselective partial agonist ; heart rate ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the partial agonist activity of cicloprolol in man, four studies were carried out in normal male volunteers. I and II. Open dose escalating studies of the effects of oral doses of the drug on exercise tachycardia and sleeping heart rate. III and IV. Double-blind randomized studies of the effects of placebo, cicloprolol 25 mg, cicloprolol 50 mg, cicloprolol 100 mg, atenolol 50 mg, pindolol 10 mg, salbutamol 8 mg and prenalterol 50 mg on sleeping heart rate, resting supine heart rate, blood pressure, forearm blood flow, finger tremor and exercise tachycardia. All doses of cicloprolol above 2.5 mg reduced an exercise tachycardia but there was no increase in effect above a dose of 50 mg. Cicloprolol caused a dose dependent increase in sleeping heart rate up to 200 mg. Cicloprolol increased resting supine heart rate, systolic blood pressure, forearm blood flow and finger tremor. None of the drugs affected quality of sleep. Cicloprolol has significant partial agonist activity at the beta1-adrenceptor as indicated by increases in heart rate and systolic blood pressure. The increases in finger tremor and forearm blood flow suggest that cicloprolol has some partial agonist activity at the beta2-adrenoceptor.
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  • 3
    ISSN: 1432-1041
    Keywords: atenolol ; ICI 118551 ; propranolol ; beta1-/beta2-adrenoceptors ; selectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the contribution of beta1- and beta2-adrenoceptors to the isoprenaline-induced changes in heart rate, blood pressure, forearm blood flow, peripheral vascular resistance, and finger tremor. This was achieved by a comparison of the effects of atenolol 50 mg, ICI 118551 25 mg, propranolol 80 mg, atenolol 50 mg combined with ICI 118551 25 mg, propranolol 80 mg combined with ICI 118551 25 mg, and placebo. Atenolol 50 mg and ICI 118551 25 mg caused similar attenuations in the isoprenaline-induced changes in heart rate and diastolic blood pressure, but the responses after the combination of atenolol and ICI 118551 were similar to those after propranolol 80 mg. There was no difference in the forearm blood flow responses to isoprenaline after atenolol 50 mg and ICI 118551, but atenolol 50 mg did not reduce peripheral vascular resistance compared with placebo. Both responses after treatment with atenolol combined with ICI 118551 were similar to those after propranolol 80 mg. Finger tremor responses to isoprenaline were antagonized by ICI 118551 alone and in combination with propranolol and atenolol but not by atenolol alone, suggesting that the response is beta2-adrenoceptor-mediated. We conclude that the cardiovascular responses to isoprenaline are mediated by both beta1- and beta2-adrenoceptors, whereas the finger tremor response is mediated by beta2-adrenoceptors.
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  • 4
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
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  • 5
    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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  • 6
    ISSN: 1432-1041
    Keywords: cimetidine ; peptic ulcer ; duodenal ulcer ; gastric ulcer ; hiatal hernia ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Between 1972 and 1980 Hospital Activity Analysis from 5 Northern Ireland Hospitals demonstrated a gradual increase in the number of patients discharged for all diagnoses whilst there was a decline in discharges for peptic ulcer related disease, (duodenal ulcer, gastric ulcer, gastrojejunal ulcer, peptic ulcer site unspecified and hiatal hernia). The mean number of peptic ulcer related disease discharges per year for 1977–80, when cimetidine became generally available, was 10% lower than that of 1972–76, mainly due to a decline in male patient numbers. The mean annual number of male patients with a duodenal ulcer fell significantly by 18% (U=1,p≤0.025) during the 1977–80 period, whereas female discharges decreased by only 4%. Between 1972–76 and 1977–80 the mean annual number of duodenal ulcer perforations decreased significantly by 21% in males but only by 4% in females. Surgery for peptic ulcer related disease was 47% less in 1977–80 period, with significant decreases in duodenal ulcer, gastric ulcer and hiatal hernia procedures. From 1977 to 1980 there was considerable growth in Northern Ireland general practice cimetidine prescribing with 300,000 prescriptions being dispensed over the period. Apart from male duodenal ulcer cases, hospitalisation for peptic ulcer related diseases did not decrease substantially after the introduction of cimetidine but duodenal ulcer perforation and conditions warranting surgery did decline.
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  • 7
    ISSN: 1432-1041
    Keywords: bufuralol ; propranolol ; pindolol ; peripheral blood flow ; systemic blood pressure ; beta-adrenoceptor antagonist ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, single oral dose, crossover study, the effects of bufuralol (60 mg) on heart rate, blood pressure, and peripheral vascular responses were compared with those of propranolol (160 mg), pindolol (10 mg), and placebo in a group of 12 healthy volunteers. All three beta-adrenoceptor antagonists reduced exercise tachycardia, but at the doses chosen the effects of bufuralol were less than those of propranolol. Forearm blood flow was reduced by propranolol and pindolol, but not by bufuralol. The antihypertensive and peripheral vascular effects of bufuralol (30–60 mg bd) were also compared with those of propranolol (40–80 mg bd) in a double-blind crossover study in 10 patients with mild hypertension. Propranolol and bufuralol produced comparable reductions in systemic blood pressure over a two-week period, but the decreases in forearm and finger blood flow were greater with propranolol. These studies suggest that bufuralol is a beta-adrenoceptor antagonist with antihypertensive properties, and that it produces less peripheral vasoconstriction than propranolol or pindolol.
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  • 8
    ISSN: 1432-1041
    Keywords: propranolol ; atenolol ; baroreflex function ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute administration of the β-adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers. Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p〈0.05) to the left compared to placebo.
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  • 9
    ISSN: 1432-1041
    Keywords: alfuzosin ; prazosin ; alpha1-adrenoceptor antagonist ; noradrenaline ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open dose ranging study with random inclusion of placebo, alfuzosin (α1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1–2 h; Cmax (4.1 to 20.8 ng · ml−1; AUC (0–24) 20 to 132 ng · ml−1 · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4. Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) for prazosin was 2.6 and 2.9 h. In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 81 (1969), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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