Different Effects of Exercise on Plasma Concentrations of Nebivolol, Bisoprolol and Carvedilol

Stoschitzky, Kurt; Stoschitzky, Gergana; Klein, W.; Bühring, Karl; Lamprecht, Günther; Lindner, Wolfgang

doi:10.1023/b:card.0000029031.87129.05

Cited by 16 publications

(12 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 52%

“…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]. However, it was shown recently that plasma concentrations of carvedilol [36, 37] and nebivolol [29] do not increase during exercise, thus being a further major difference between third generation beta-blockers and those of the first and second generation [38]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Stoschitzky¹,

Stoschitzky²,

Brussee³

et al. 2006

Cardiology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Stoschitzky¹,

Stoschitzky²,

Brussee³

et al. 2006

Cardiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast to most other BAAs, nebivolol is not taken up into, stored in and released from adrenergic cells during exercise together with epinephrine and norepinephrine. Exercise had no effect on plasma concentrations of nebivolol (rest: 0.273 ± 0.029 ng/mL, exercise: 0.274 ± 0.035 ng/mL, recovery: 0.272 ± 0.035 ng/mL) . This might explain why other BAAs are still effective after withdrawal even when they are no longer detectable in plasma.…”

Section: Methodsmentioning

confidence: 94%

Nebivolol in the treatment of arterial hypertension

Olawi

Krüger

Grimm

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

This MiniReview reports the current knowledge about the treatment of arterial hypertension with the third‐generation beta‐adrenoceptor antagonist (BAA) nebivolol. Furthermore, it reviews the advantages of nebivolol compared to the earlier generation of BAAs with respect to their different pharmacological properties. Beta‐adrenoceptor antagonists are a class of drugs applied for several different conditions, including hypertension and heart failure. They differ significantly in their pharmacological properties, including varying β1/β2‐selectivity and/or exertion of additive effects on the heart and circulation. Although these drugs have been a part of hypertensive therapy for about 40 years, the outcome of large clinical trials has put the role of BAAs into question. However, most of these results were based on first‐ and second‐generation BAAs and cannot be translated directly into third‐generation drugs. The third‐generation BAA nebivolol has the highest β1‐selectivity seen so far, together with additional vasodilating and anti‐oxidative properties. It is currently applied in the treatment of hypertension and congestive heart failure. Nebivolol has a unique pharmacological profile, despite showing similar blood pressure‐lowering effects, and has certain advantages in the treatment of hypertension compared to the previous generations of BAAs. This includes significant improvements in endothelial dysfunction, central haemodynamics and the degree of erectile dysfunction in men, a neutral/beneficial metabolic profile and lastly a more favourable side effect profile. It is widely beneficial for, for example, sexually active men and patients with comorbidities such as type II diabetes mellitus, metabolic syndrome and chronic obstructive lung disorders. Whether the advantages translate to an improved long‐term clinical outcome remains to be clarified, and ongoing prospective studies will show this in the future.

show abstract

“…Also similar to nebivolol, plasma concentrations of carvedilol do not increase during exercise [8], thus indicating that carvedilol is not concomitantly released with adrenaline and noradrenaline from adrenergic cells during exercise [12,13], another finding unique to carvedilol and nebivolol among all ß-blockers so far investigated.…”

Section: Carvedilolmentioning

confidence: 85%

“…However, plasma concentrations of nebivolol do not increase during exercise [8], thus indicating that nebivolol is not concomitantly released from adrenergic cells during exercise with adrenaline and noradrenaline. 25 mg carvedilol (Carved) racemate and 5 mg nebivolol (Nebiv) racemate on nocturnal excretion of 6-sulfatoxy-melatonin (a6MTS, the main metabolite of melatonin that is almost completely released in urine): The ß-blocking (S)-enatiomers of propranolol and atenolol decreased aMT6s by more than 80%, whereas the non-ß-blocking (R)-enantiomers of propranolol and atenolol as well as the racemic mixtures of carvedilol and nebivolol had no effect.…”

Section: Nebivololmentioning

confidence: 86%

Additional Features of Beta-Blockers

Stoschitzky¹

2005

Heart Drug

Self Cite

View full text Add to dashboard Cite

The predominant action of β-blockers is their inhibition of the stimulating effects of adrenaline and noradrenaline on sympathetic β-adrenoceptors. In this context, they are particularly useful in the treatment of arterial hypertension, coronary artery disease, myocardial infarction, tachyarrhythmias and heart failure. However, a number of β-blockers also exert additional effects independent from the inhibition of β-receptors: nebivolol causes NO-derived vasodilation, carvedilol also inhibits sympathetic α-receptors, sotalol shows additional antiarrhythmic class III effects, and propranolol inhibits the conversion of thyroxine to triiodothyronine and shows slight antiarrhythmic class I effects. In addition, β-blockers may be used in the treatment of other diseases such as hyperthyroidism, migraine, essential tremor, portal hypertension, hypertrophic obstructive cardiomyopathy and aortic dissection. As a special feature, most β-blockers are taken up into, stored in and released from adrenergic cells together with adrenaline and noradrenaline. Consequently, plasma concentrations of these drugs are markedly increased during exercise together with those of adrenaline and noradrenaline and remaining β-blocking effects long after the withdrawal of chronic administration of β-blockers, even when they are no longer detectable in plasma. Furthermore, except for nebivolol and carvedilol, all β-blockers investigated in this context inhibit the nocturnal production and release of melatonin. Finally, all β-blockers currently used in the treatment of cardiovascular diseases are racemic mixtures consisting of (R)- and (S)-enantiomers in a fixed 1:1 ratio although they may show different pharmacokinetics, and only the (S)-enantiomers cause β-blockade whereas the (R)-forms do not contribute to this effect but may increase side effects and drug interactions. Thus, β-blockers may exert a number of interesting features in addition to their well-known effects on cardiac β-adrenoceptors.

show abstract

Different Effects of Exercise on Plasma Concentrations of Nebivolol, Bisoprolol and Carvedilol

Cited by 16 publications

References 12 publications

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Nebivolol in the treatment of arterial hypertension

Additional Features of Beta-Blockers

Contact Info

Product

Resources

About