Additional Features of Beta-Blockers

Abstract

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.

Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

“…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]. …”

High Selective Long-Acting Β1-Blocker With a Vasodilating Effect Nebivolol in Patients With Chronic Ischemic Heart Disease

“…Небиволол (Небилет ® ) приводил к улучшению эндотелиальной функции: достоверно повышал активность эндотелиальной NO-синтазы в культуре клеток и уровень стабильных метаболитов NO в сыворотке крови, достоверно увеличивал эндотелий-зависимую вазодилатацию [54,55].…”

Box‐Behnken response surface modeling assisted enantiomeric resolution of some racemic β‐blockers using HPTLC and β‐cyclodextrin as chiral mobile phase additive: Application to check the enantiomeric purity of betaxolol

“…It was proved that optically pure (+) SOT enantiomer caused high mortality rate as it only exerts antiarrhythmic class III activity without beta‐blocking effects. Thus, β‐blocking activity which is exerted only by the (−) enantiomer plays a vital role in both safety and efficacy of SOT …”

“…Thus, β-blocking activity which is exerted only by the (−) enantiomer plays a vital role in both safety and efficacy of SOT. 5 Separation of BET, CAR, and SOT enantiomers has been reported using HPLC with chiral stationary phase 6 and capillary electrophoresis. 7 Compared with these reported chromatographic techniques, High Performance Thin Layer Chromatography (HPTLC) shows the advantages of low expenses, simplicity of performance, and possibility of running several samples in the same run using small amount of solvents making it more ecofriendly.…”