The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study

Choi, Yoon-Dong; Park, Kyu Hee; Park, Ju Yeon; Min, Won Kee; Lee, Yoon Sook

doi:10.1016/j.bjane.2021.04.005

Cited by 1 publication

(2 citation statements)

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“…Among the total candidates, three genes are known to be responsible for the pharmacokinetics of DXM ( CYP2A6 , UGT1A4 , UGT2B10 ) ( Holliday et al, 2014 ; Ber et al, 2020 ), and ten analyzed genes were speculated to be associated with DXM pharmacokinetics ( ABCG2 , ABCB1 , ABCC2 , ABCC3 , SLCO1B1 , SLC22A1 , CYP1A2 , CYP2C19 , CYP2D6 , and WBP2NL ). Additionally, the ADRA2A gene has been demonstrated to participate in the primary mechanism of DXM action ( Zhu et al, 2019 ; Choi et al, 2021 ). The remaining fourteen genes were hypothesized to be involved in the pharmacodynamics of DXM ( SLC31A1 , KATP , KCNJ11 , KCNMB1 , KCNMA1 , KCNN4 , CACNA1D , CACNA1C , ABCC9 , ADRB2 , COMT , GNB3 , PRKCB , and PRKCH ).…”

Section: Methodsmentioning

confidence: 99%

“…Direct N-glucuronidation by uridine 5′-diphospho-glucuronosyltransferase (UGT2B10 and UGT1A4) and hydroxylation mediated by cytochrome P450 (CYP) enzymes (CYP2A6) constitute the main metabolic pathways ( Ber et al, 2020 ). Sedative and hypnotic effects resembling natural sleep by DXM are thought to be mediated through the activation of central pre- and post-synaptic α2 adrenergic receptors in the locus coeruleus ( Choi et al, 2021 ). Additionally, DXM regulates vasoconstriction or vasodilation by binding with α2 receptors in several structures ( De Cassai et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

Ding,

Liu,

Wang

et al. 2023

Front. Genet.

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Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences.Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype.Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation.Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.

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