The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra-short-acting β1 adrenergic receptor antagonist esmolol in healthy individuals

Muszkat, Mordechai; Hoofien, Assaf; Orlanski-Meyer, Esther; Makhoul, Hani; Porat, Einav; Davidson, Elyad; Blotnick, Simcha; Caraco, Yoseph

doi:10.1097/fpc.0b013e32835afde6

Cited by 10 publications

(4 citation statements)

References 12 publications

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“…8 A second non-synonymous SNP, rs1801252, resulting in the Ser49Gly variant in the extracellular amino terminal end of β 1 -AR, is associated with increased agonist-promoted receptor down-regulation in transfected cell lines. 9 Accordingly, a number of translational 10-12 and clinical studies in patients with hypertension, AF, and heart failure with reduced ejection fraction have found genotype-dependent responses to BBs. 13-19 …”

Section: Introductionmentioning

confidence: 99%

Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery

Jeff

Donahue

Brown-Gentry

et al. 2014

American Heart Journal

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Background: Postoperative atrial fibrillation (PoAF) after cardiac surgery is common and associated with increased morbidity and mortality. Increased sympathetic activation after surgery contributes to PoAF, and beta-blockers are the first-line recommendation for its prevention. We examined the hypothesis that common functional genetic variants in the β1-adrenoreceptor, the mediator of cardiac sympathetic activation and drug target of beta-blockers, are associated with the risk for PoAF and with the protective effect of beta-blockers. Methods: In a prospective cohort study, we studied 947 adult European Americans who underwent cardiac surgery at Vanderbilt University between 1999-2005. We genotyped two variants in the β1-adrenoreceptor, rs1801253 (Arg389Gly) and rs1801252 (Ser49Gly), and used logistic regression to examine the association between genotypes and PoAF occurring within 14 days after surgery, before and after adjustment for demographic and clinical covariates. Results: PoAF occurred in 239 patients (25.2%) and was associated with rs1801253 genotype (adjusted P=0.008), with Gly389Gly having an odds ratio of 2.63 (95% confidence interval, 1.42 to 4.89) for PoAF compared to the common Arg389Arg (P=0.002). In a predefined subgroup analysis, this association appeared to be stronger among patients without beta-blocker prophylaxis (adjusted OR=7.00; 95% CI, 1.82 to 26.96; P=0.005) compared to patients with beta-blocker prophylaxis, among whom the association between rs1801253 genotype and PoAF was not statistically significant (adjusted P=0.11). Conclusion: The Gly389 variant in the β1-adrenoreceptor is associated with PoAF, and this association appears to be modulated by beta-blocker therapy. Future studies of the association of other adrenergic pathway genes with PoAF will be of interest.

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Section: Introductionmentioning

confidence: 99%

Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery

Jeff

Donahue

Brown-Gentry

et al. 2014

American Heart Journal

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“…Racial/ethnic differences in responsiveness to beta blockers have been noted 33 and genetic subtype of beta-1 receptor can lead to different HR response. 34 Although there are no racial/ethnic differences in the pharmacokinetic parameters of landiolol, 13 , 26 , 27 , 35 these preliminary results in Caucasians appear to confirm no difference in its pharmacodynamics. However, further studies are needed to identify the appropriate dose for acute rate control in larger cohorts.…”

Section: Dosage Of Landiololmentioning

confidence: 73%

Benefits and safety of landiolol for rapid rate control in patients with atrial tachyarrhythmias and acute decompensated heart failure

Shiga

2022

European Heart Journal Supplements

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Atrial tachyarrhythmias often occur in patients with worsening heart failure (HF), and the development of atrial tachyarrhythmias in acute decompensated HF (ADHF) causes an uncontrolled heart rate (HR) and leads to further exacerbation of HF and persistence of a decompensated HF state. Landiolol, a short-acting intravenous beta-1 blocker, shows very high cardiac beta-1 selectivity and has a very short elimination half-life of approximately 4 min. As shown in several reports, the benefit of intravenous landiolol is that it lowers the ventricular rate early after the start of use without markedly deteriorating haemodynamics. After the cardiac status is stabilized by rapid control of HR, subsequent basic HF pharmacotherapy and rhythm control therapies will be effective for improving outcomes. Because of the pharmacokinetic properties of landiolol, if the patient suffers an adverse reaction such as hypotension or bradycardia, such effects can be quickly reversed by tapering the dose or discontinuing use altogether. Based on several clinical studies, this review discusses the efficacy, safety and role of intravenous landiolol in acute HR control in patients with atrial tachyarrhythmias and ADHF.

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“…46 Another study indicates a 10 times difference in the effects of Esmolol on exercise- induced tachycardia in people with ADRB1 389 genotype. 47 Furthermore, according to previous studies, in people with ADRb1-389 Arg/Arg genotype, a higher dose of beta blocker is needed to achieve a treatment response rather than in people with Gly genotype carriers. 48 …”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

Salehifar¹,

Ebrahim²,

Shiran³

et al. 2017

Adv Pharm Bull

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Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not.Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm.Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value<0.001).Conclusion: This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol.

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The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra-short-acting β1 adrenergic receptor antagonist esmolol in healthy individuals

Cited by 10 publications

References 12 publications

Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery

Genetic variation in the β1-adrenergic receptor is associated with the risk of atrial fibrillation after cardiac surgery

Benefits and safety of landiolol for rapid rate control in patients with atrial tachyarrhythmias and acute decompensated heart failure

Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

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