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Review
. 2024 Mar 20;15(3):379.
doi: 10.3390/genes15030379.

Pediatric Beta Blocker Therapy: A Comprehensive Review of Development and Genetic Variation to Guide Precision-Based Therapy in Children, Adolescents, and Young Adults

Mollie Walton  1 , Jonathan B Wagner  1   2   3
Affiliations
Review

Pediatric Beta Blocker Therapy: A Comprehensive Review of Development and Genetic Variation to Guide Precision-Based Therapy in Children, Adolescents, and Young Adults

Mollie Walton et al. Genes (Basel). .

Abstract

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review is to illustrate the current knowledge gaps regarding the key drivers of variability in beta blocker drug disposition and response and the opportunities for investigations that will lead to changes in pediatric drug labeling.

Keywords: beta-blockers; pediatrics; pharmacogenomics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Dose–Exposure–Response Pathway. Red dashed line delineates the dose–exposure (drug disposition) relationship. Figure created with Biorender.com. Abbreviations: MATE—Multidrug and Toxin Extrusion, MDR1—Multidrug Resistance Protein 1, MRP2—multidrug resistance-associated protein 2, OATP—organic anion transporter polypeptides, OCT—organic cation transporter, P-gp—P-glycoprotein.
Figure 2
Figure 2
Beta Adrenergic Signaling Cascade. Activation of ADRB1 results in a signaling cascade leading to enhanced chronotropy and inotropy. Additionally, it can stimulate calmodulin-dependent protein kinase II (CaMKII) to result in apoptosis. Figure created with Biorender.com. Abbreviations: ADRB1—β1 adrenergic receptor, ATP—adenosine triphosphate, CaMKII—calmodulin-dependent protein kinase II, cAMP—cyclic adenosine monophosphate.
Figure 3
Figure 3
Adrenergic Beta Receptor Type 1. Structure and sites of significant polymorphism. Figure created with Biorender.com.
See this image and copyright information in PMC

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