Exercise‐induced increments in plasma levels of propranolol and noradrenaline.

Hurwitz, Gilbert A.; Webb, Jerry G.; Walle, Thomas; Bai, Stephen A.; Daniell, Herman B.; Gourley, L; Loadholt, C B; Gaffney, Thomas E.

doi:10.1111/j.1365-2125.1983.tb02228.x

Cited by 31 publications

(15 citation statements)

References 28 publications

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“…In addition to the different effects of beta-blockers obtained in the present study, it was shown recently that pharmacokinetic properties of third generation beta-blockers also differ significantly from those of first and second generation beta-blockers: It was shown previously that plasma concentrations of propranolol, atenolol and bisoprolol markedly increase during exercise [25,26,27,28,29]. The reason for this increase might be the fact that propranolol and atenolol are taken up into, stored in and released from adrenergic cells during exercise together with epinephrine and norepinephrine, thus causing an increase of plasma concentrations of these drugs together with those of epinephrine and norepinephrine during exercise [30,31,32,33,34,35].…”

Section: Discussionmentioning

confidence: 93%

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Stoschitzky¹,

Stoschitzky²,

Brussee³

et al. 2006

Cardiology

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Objective: Bisoprolol, carvedilol and nebivolol have been shown to be effective in the treatment of heart failure. However, the beta-blocking effects of these drugs have never been compared directly. Methods: Therefore, we performed a randomized, double-blind, placebo-controlled, cross-over trial in 16 healthy males. Subjects received 10 mg bisoprolol, 50 mg carvedilol, 10 mg nebivolol and placebo on the first morning followed by 5 mg bisoprolol once daily, 25 mg carvedilol twice daily, 5 mg nebivolol once daily and placebo for 1 week. Heart rate and blood pressure were measured at rest and exercise 3 and 24 h following intake of the first dose, and immediately before and 3 hours following intake of the last dose of each drug. In addition, effects of the drugs on nocturnal melatonin release were determined, and quality of life (QOL) was evaluated. Results: Heart rate at exercise was decreased at 3 h following intake of the first single dose of each drug by bisoprolol (–24%), carvedilol (–17%) and nebivolol (–15%), and at 24 h following intake of the respective last dose of each drug following 1 week of chronic administration by bisoprolol (–14%), carvedilol (12 h; –15%) and nebivolol (–13%) (p < 0.05 in all cases). Thus, trough-to-peak-ratios at long-term were as follows: Bisoprolol, 58%; carvedilol (12 h), 85%; nebivolol, 91%. Nocturnal melatonin release was decreased by bisoprolol (–44%, p < 0.05) whereas nebivolol and carvedilol had no effect. QOL with carvedilol was slightly but significantly lower than with the other drugs, whereas bisoprolol and nebivolol did not alter QOL. Conclusions: These data show that peak beta-blocking effects of bisoprolol appear stronger than those of nebivolol and carvedilol. On the other hand, nebivolol exerts the highest trough-to-peak-ratio. However, beta-blocking effects of all the three drugs are similar at trough. Only bisoprolol but neither nebivolol nor carvedilol decreased nocturnal melatonin release, a feature which might cause sleep disturbances. Finally, only carvedilol slightly decreased QOL, whereas nebivolol and bisoprolol did not affect QOL. We conclude that different beta-blockers may exert clinically relevant different effects.

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Section: Discussionmentioning

confidence: 93%

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Stoschitzky¹,

Stoschitzky²,

Brussee³

et al. 2006

Cardiology

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“…Nerve-stimulation induced release of propranolol was also observed in the spleen and the vasculature of the perfused canine hindlimb (Russell et al, 1983). Similarly, in man, treadmill exercise was found to produce a simultaneous elevation of propranolol and NA in the plasma of hypertensive patients and normal volunteers receiving therapeutic doses of drug (Hurwitz et al, 1983). Thus, propranolol release in association with sympathetic nerve stimulation appears to represent a generalized phenomenon at adrenergic neuroeffector junctions and, conceivably, may contribute to pharmacological actions of the drug at vascular and other synapses.…”

Section: Introductionmentioning

confidence: 90%

Depolarization‐induced release of propranolol and atenolol from rat cortical synaptosomes

Bright¹,

Gaffney

Street³

et al. 1985

British J Pharmacology

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The accumulation and release of [3H]‐propranolol and [3H]‐atenolol were examined in synaptosomes from rat cerebral cortex. Synaptosomes accumulated 20 pmol propranolol and 0.6 pmol atenolol mg−1 protein when incubated at 30°C with radiolabeled drugs (0.1 μm). Exposure of propranolol‐loaded synaptosomes to elevated K+, Rb+ or Cs+ evoked a concentration‐dependent increase in propranolol efflux. The action of these ions in releasing propranolol was highly correlated with their ability to produce synaptosomal membrane depolarization, as estimated with the voltage‐sensitive dye diS‐C3‐(5). Elevated K+ also promoted atenolol release from synaptosomes in a concentration‐dependent manner. Veratridine (10 μm) released propranolol and atenolol from synaptosomes and these effects were antagonized by tetrodotoxin (1 μm). Under Ca2+‐free conditions, K+‐induced release of propranolol was reduced by 37% and atenolol release was diminished by 68%. The results support the concept that both polar and non‐polar β‐adrenoceptor blocking drugs may be accumulated by nerve endings for release by membrane depolarization and suggest that neural storage and release of these molecules may influence their concentrations at localized sites of action.

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“…Mean plasma oxprenolol concentrations 24 h after dosing were 100-250 ng ml-', and in all subjects terminal plasma concentrations exceeded 50 ng ml-', levels at which adequate P-adrenoceptor blockade can be maintained (Theeuwes et al, 1985). Transient exercise induced increases in plasma levels of lipophilic ,-adrenoceptor antagonists have been reported in animals (Powis & Snow, 1978) and in normal human subjects (Hurwitz et al, 1983). These changes may reflect redistribution of 3-adrenoceptor antagonists at site(s) of action (evidence cited by Hurwitz et al, 1983).…”

Section: Discussionmentioning

confidence: 67%

“…Transient exercise induced increases in plasma levels of lipophilic ,-adrenoceptor antagonists have been reported in animals (Powis & Snow, 1978) and in normal human subjects (Hurwitz et al, 1983). These changes may reflect redistribution of 3-adrenoceptor antagonists at site(s) of action (evidence cited by Hurwitz et al, 1983). The increases in plasma oxprenolol concentrations (mean 2.5%) were smaller than those reported for propranolol (13-14%) by Hurwitz et al (1983), although these may represent only a fraction of the changes at receptor sites.…”

Section: Discussionmentioning

confidence: 87%

Concentration‐effect relationships for oxprenolol in patients with essential hypertension.

McInnes

Brodie

1988

Brit J Clinical Pharma

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1 Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2 Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P < 0.001), but differences were slight. 3 Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4 The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.

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Exercise‐induced increments in plasma levels of propranolol and noradrenaline.

Cited by 31 publications

References 28 publications

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Depolarization‐induced release of propranolol and atenolol from rat cortical synaptosomes

Concentration‐effect relationships for oxprenolol in patients with essential hypertension.

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