Additional Features of Beta-Blockers

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.