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Recent advances in the treatment of renal diseases with nebivolol: A literature review

https://doi.org/10.1016/j.nephro.2016.01.011Get rights and content

Abstract

Reactive oxygen species play an important role in both acute and chronic kidney diseases. Chronic kidney disease is associated with various consequences to the cardiovascular system and metabolic profiles. Nebivolol, a highly cardioselective third-generation β-blocker, has nitric oxide (NO) induced vasodilation and antioxidant properties. Nebivolol affects the endothelial NO pathway in two complementary ways: it increases endothelial mediated NO expression and has antioxidant action, which leads to a decrease in degradation. Central blood pressure can be effectively lowered by nebivolol in the prehypertension phase. Clinically nebivolol's ability to modulate endothelial dysfunction may offer additional vascular protection in treating hypertension. As well, pre-treatment with 5 mg nebivolol every 24 hours for 4 days is protective against nephrotoxic effects of contrast media. The aim of this study is to review the current literature on the efficacy and safety of nebivolol in the treatment of various states of renal diseases.

Introduction

Beta-blockers are the second line agents in treatment of hypertension excluding patients with coronary artery diseases as well as it has not been received the Food and Drug Administration (FDA) approval in patients with heart failure. Nebivolol is a novel β-blocker that has been available for a number of years for the treatment of hypertension, either taken alone or in combination with other antihypertensive agents. It is a third-generation β-blocker that exhibits highly selective β1-adrenergic receptor blockade and nitric oxide mediated vasodilation. The beneficial effects of nebivolol as an antihypertensive treatment are not associated with the usual side effects of other β-blockers. Nebivolol was also shown to interfere with amyloid-β protein precursor (AβPP) processing in neuronal like cells and exert estrogen like neuroprotective effects. Animal study by Wang et al. showed that chronic application of nebivolol is highly tolerable and safe and can significantly reduce neuropathology in the brain, which is one of the most important parameters for primary prevention of Alzheimer's disease (AD) [1].

Section snippets

Method

This paper has written in accordance with review of systematic literature search via PubMed from inception to December 2015 and Google Scholar using medical subject headings that combined with terms for acute kidney injury or chronic kidney disease. Then this method supplemented with author's working knowledge and reference lists of review article and textbooks, and with references in articles that author found relevant.

Pharmacodynamics

Generally, in pharmacology references beta-blockers are categorized as cardioselective (atenolol, bisoprolol, metoprolol, nebivolol), non-selective (nadolol, propanolol, timolol), intrinsic sympathomimetic activity (acebutolol, carteolol, penbutolol, pindolol) and mixed α- and β-blockers (carvedilol, labetalol). Currently, based on receptor affinity and hemodynamic properties, available β-blockers can be categorized into one of four principle groups: non-cardioselective and non-vasodilatory,

Clinical efficacy

The FDA's approval of nebivolol was based on its hypertensive effectiveness in the two pivotal randomized, double-blind, multicenter, placebo-controlled trials conducted in the United States (US). Both studies concluded that nebivolol was safe, well tolerated and effective for patients with mild to moderate hypertension [2]. Now clinical efficacy of nebivolol is discussed in the following states.

Adverse effects of nebivolol

Based on product insert monograph (Forest Laboratories Canada Inc. 2014) in placebo-controlled monotherapy trials, the most common adverse events (> 2% patients) observed with BYSTOLIC were headache (7.1%), fatigue (3.6%), nasopharyngitis (3.1%), dizziness (2.9%), diarrhoea (2.5%) and upper respiratory tract infections (2.1%). Other adverse drug effects (less than 1%) such as diabetes mellitus, gout, hypercholesterolemia, hyperkalemia, hyperlipidemia, depression, bradycardia, myocardial

Drug interactions

Co-administration with fluoxetine (also metabolized by CYP2D6) in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol [50]. There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of drug [51]. Furthermore, in interaction of nebivolol with anti-epileptic drugs, it showed anti-epileptic effect in addition to its reported antihypertensive effect. Thus the

Conclusion

Oxidative stress plays a large role in the development of resistant or difficult-control hypertension as well as contributing to end organ damage such as cardiovascular disease, stroke and chronic kidney disease. Nebivolol attenuates the endothelial dysfunction and the vascular oxidative stress. Furthermore, it lowers the L-NAME induced high LDL levels. Nebivolol can now be added to list of the third-generation beta-blockers because of antioxidant properties and free radical scavenging ability

Disclosure of interest

The author declares that she has no competing interest.

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