Mason R Preston, Giles Thomas D, Sowers James R
Cardiovascular Division, Department of Medicine Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
J Cardiovasc Pharmacol. 2009 Aug;54(2):123-8. doi: 10.1097/FJC.0b013e3181ad207b.
Beta (beta) blockers are widely used for treatment of cardiovascular and noncardiovascular diseases. Nevertheless, their mechanism of action is not fully understood and differs significantly among agents in this class. Chronic increases in adrenergic activity in heart failure result in desensitization of cardiac beta-adrenergic receptor signal transduction and adverse effects on myocytes. By reducing heart rate and decreasing myocardial workload, the pathologic remodeling of the heart may be reversed with beta-blocking agents. Among beta-blockers, there are clear differences in pharmacodynamic and pharmacokinetic properties. Newer beta-blockers differ from older agents with respect to beta-adrenoceptor affinity and selectivity and partial agonist activity, which may affect their mechanism of action and be important in clinical use.The first beta-antagonist compounds were nonselective; the next generation of beta-blockers was selective for beta1-receptors. The most recent beta-blockers may be nonselective or selective, and they have the additional ancillary property of vasodilation. Nebivolol is among the newer third-generation beta-blockers. It is unique in the class, since apart from its cardioselectivity, it also produces nitric oxide-mediated vasodilation. As a result, its hemodynamic profile is clearly different from those of traditional beta-blockers. This review will evaluate this class of agents and the basis for their differences in clinical use.
β受体阻滞剂广泛用于治疗心血管疾病和非心血管疾病。然而，其作用机制尚未完全明确，且该类药物之间存在显著差异。心力衰竭时肾上腺素能活性的慢性增加会导致心脏β肾上腺素能受体信号转导脱敏，并对心肌细胞产生不良影响。通过降低心率和减少心肌工作量，β受体阻滞剂可能会逆转心脏的病理重塑。在β受体阻滞剂中，药效学和药代动力学特性存在明显差异。新型β受体阻滞剂在β肾上腺素能受体亲和力、选择性和部分激动剂活性方面与旧型药物不同，这可能会影响其作用机制，在临床应用中具有重要意义。第一代β受体拮抗剂化合物是非选择性的；下一代β受体阻滞剂对β1受体具有选择性。最新的β受体阻滞剂可能是非选择性的或选择性的，并且具有血管舒张的附加辅助特性。奈必洛尔属于新型第三代β受体阻滞剂。它在该类药物中独具特色，因为除了具有心脏选择性外，它还能产生一氧化氮介导的血管舒张作用。因此，其血流动力学特征与传统β受体阻滞剂明显不同。本综述将评估这类药物及其临床应用差异的依据。
