Comparative properties of various beta-blockers, with an outlook to the future.
Several beta-adrenoceptor blockers with various ancillary properties besides beta-receptor blockade are now available for clinical use. In the treatment of hypertension, angina pectoris, and certain types of cardiac arrhythmia the therapeutic benefit is mediated by beta 1-receptor blockade, whereas the blockade of beta 2-adrenoceptors does usually not contribute to the therapeutic efficacy and is rather associated with adverse reactions. Accordingly, all properties other than beta 1-adrenoceptor blockade should be considered as ancillary properties. The following properties of beta-blockers and the therapeutic relevance of these properties are to be discussed, together with pertinent examples of the drugs involved: beta 1-receptor selectivity and the degree of beta 2-receptor blockade; intrinsic sympathomimetic activity (ISA); duration of action (to be discussed in connection with the pharmacokinetic properties in Prof. Borchard's presentation); lipophilicity, brain penetration and CNS side effects, and cardioprotective properties (secondary prevention following myocardial infarction). Most of these properties have been investigated in full detail and a wide variety of compounds possessing one or more of these properties have been introduced. With respect to the future, beta 1-adrenoceptor selectivity remains an interesting issue, although it is difficult to imagine that compounds which are even more beta 1-selective than bisoprolol can be developed. The cardioprotective activity of beta-blockers deserves further investigations, in particular with respect to the underlying mechanisms. Finally, many new beta-blockers are now becoming available with an additional vasodilator component which may be caused by different mechanisms, like 'direct' vasodilation, beta 2-receptor agonism, alpha-adrenoceptor blockade, or angiotensin-converting enzyme inhibition. The various mechanisms and possible clinical relevance will be discussed.
van Zwieten
P A
PA
Department of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000758:Anesthesia; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002462:Cell Membrane / Q000187:drug effects; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta