ReviewThe Evolving Role of β-Adrenergic Receptor Blockers in Managing Hypertension
Section snippets
Drug Development
During the last 50 years, new techniques involving molecular pharmacology and radioligands have allowed more precise definition of the nature and role of the different subtypes of adrenoreceptors.14 Using pharmacologic, biochemical, and molecular biological techniques, 3 subtypes of β-adrenergic receptors have now been well characterized.15 The β1 receptor is mainly found in the heart, where it represents 75%-80% of the β-adrenoreceptor mass. The β2 receptor predominates in a number of sites
Mechanisms of Action
Pharmacological agents that block β-adrenergic receptors act quite differently depending on the receptor subtypes they target.15 In general, nonselective agents like propranolol nonselectively block both β1 and β2 receptors. By blocking β1 receptors, they reduce heart rate, nodal conduction velocity, and contractility. On the other hand, by blocking β2 receptors, they tend to promote vascular smooth muscle contraction and thus to increase peripheral resistance.17 Second-generation agents such
Pharmacological Characteristics
The differences in pharmacological effects introduce the concept that β-blockers represent a very heterogeneous class of antihypertensive agents.11 Indeed, β-blockers differ with respect to their β1 receptor selectivity, intrinsic sympathomimetic activity (ISA), membrane-stabilizing activity, lipophilicity, vasodilatory mechanisms and pharmacokinetic characteristics. In clinical practice, β-blockers are selected according to these characteristics. As shown in Table 2, different generations of
Clinical Efficacy of β-Blockers in Hypertension
Many studies have demonstrated the antihypertensive efficacy of the β-blockers as a class of drugs.35 In addition, other studies have demonstrated their efficacy in preventing cardiovascular events. In 2006, Khan and McAllister published a meta-analysis based on 21 trials involving more than 145,000 patients36 in response to the analysis from Lindholm et al.12 As compared with placebo, β-blockers used as first-line monotherapy reduced major cardiovascular outcomes (composite end point of death,
Drug Combinations With β-Blockers in Hypertension
As a large proportion of hypertensive patients will frequently require more than 1 medication to obtain BP control,1, 40 physicians should know which antihypertensive agent to combine with β-blockers. In terms of synergistic effects, dihydropyridine calcium channel blockers (DHP-CCB) represent a good selection to combine with β-blockers. On the one hand, the potent vasodilatory effect of DHP-CCB produces reflex tachycardia that can be counteracted by β-blockers. On the other hand, combining
Metabolic Effects of β-Blockers
Since the widespread use of β-blockers in hypertension, the metabolic tolerability profile of these agents has always been of concern. Indeed, abnormalities in glucose and insulin levels as well as in lipid and carbohydrate metabolism have been reported in several publications dealing with the effects of traditional β-blockers in pooled datasets.19, 27 With regard to lipid profile, Kasiske et al. published a meta-analysis of 474 studies regrouping more than 65,000 patients performed between
Side Effect Profile of β-Blockers
Despite compelling evidence for benefits in favour of β-blocker treatment in hypertension and a number of associated conditions, there is an ongoing reluctance for many clinicians to use these agents.18 This may be due to concerns about tolerability, and mainly to central nervous system side effects like depression, fatigue, nightmares, and sexual dysfunction. One should be cautious when using these agents in patients with asthma or chronic obstructive pulmonary disease because of the risk of
MI
Conventional β-blockers have clearly demonstrated their efficacy to reduce mortality after MI. A meta-analysis of 17 studies showed that there is a definite relationship between efficacy to reduce the incidence of MI and the reduction of heart rate at rest.28 This may explain why β-blockers with ISA have not shown efficacy in preventing new events.26
Angina pectoris
CHEP recommends conventional β-blockers as the treatment of choice in hypertension associated with angina pectoris.1 In fact, the reduction of
Are All β-Blockers Equally Effective in Hypertension?
Most authors consider the antihypertensive effect of the different β-blocking agents to be equal when administered at equipotent doses.56 Characteristics of cardioselectivity, duration of action, lipophilicity, and ISA may affect efficacy and tolerability. In the clinical setting, clinicians should choose a specific agent to optimize the tolerability profile (cardioselective agent vs asthma or Raynaud's phenomenon; less lipophilic agent vs central effects such as fatigue, insomnia; agent with
Conclusion
For many years, β-blockers have been used for the treatment of hypertension, for which they are clearly effective. Meta-analyses have also shown that they are effective in reducing cardiovascular events, especially in patients younger than 60 years of age. However, the mechanism of action of conventional β-blockers depends largely on reducing heart rate and cardiac output, which may not be optimal because there is little effect on peripheral vascular resistance, the primary abnormality in
Disclosures
No grants from the pharmaceutical industry or external sponsors have been received for this work. No conflicts of interest, financial or otherwise, are declared by the authors.
Acknowledgements
The authors thank Dr Sheldon W. Tobe for his help in reviewing the manuscript.
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2017, Journal of Chromatography ACitation Excerpt :β-Adrenergic blocking agents have been widely used for the treatment of hypertension for the past 50 years, and continue to be recommended as a mainstay of therapy in many national guidelines. They have also been used in a variety of cardiovascular conditions commonly complicating hypertension, including angina pectoris, myocardial infarction, acute and chronic heart failure, as well as conditions like essential tremor and migraine [1,2]. Most of the β-adrenergic blocking agents have one chiral carbon and so they have at least two optical isomers.
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2014, American Journal of Kidney DiseasesCitation Excerpt :The data provided a large representative sample of older adults, allowing us to estimate risk with good precision and external validity. Metoprolol tartrate was a reasonable comparator to atenolol because both are β1-cardioselective drugs and both increase vagal tone and reduce sympathetic outflow.50,51 There was a 32% RR reduction in 90-day mortality with atenolol versus metoprolol tartrate, which, if attenuated by residual confounding, may still represent a clinically important effect for a medication used long term.
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2014, Canadian Journal of CardiologyCitation Excerpt :In summary, adding an α-blocker to a β-blocker is an effective combination in patients aged 70 years and younger. β-Blockers have been used for many years to effectively treat hypertension and reduce the incidence of cardiovascular disease.24 β-Blockers combine well with DHP CCBs and α-blockers.
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