The pharmacogenetics of Medications Used in General Anesthesia

Xie, Shiyu; Ma, Wenxue; Guo, Qulian; Liu, Jie; Li, Wei; McLeod, Howard L.; He, Yijing

doi:10.2217/pgs-2017-0168

Cited by 18 publications

(22 citation statements)

References 99 publications

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“…Inhaled anesthetic and intravenous opioid analgesic agents were the most common anesthetic medications that might induce a drug–gene interaction and potentially a subsequent intraoperative adverse event [ 12 , 17 , 18 ]. Genes that were mostly interacting with anesthetic drugs were CYP2D6 , RYR1 , CYP3A4 , BChE , and G6PD [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

Zarei

Costas

Orozco

et al. 2020

JPM

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Background: Precision medicine represents an evolving approach to improve treatment efficacy by modifying it to individual patient’s gene variation. Pharmacogenetics, an applicable branch of precision medicine, identifies patient’s predisposing genotypes that alter the clinical outcome of the drug, hence preventing serious adverse drug reactions. Pharmacogenetics has been extensively applied to various fields of medicine, but in the field of anesthesiology and preoperative medicine, it has been unexploited. Although the US Food and Drug Administration (FDA) has a table of pharmacogenomics biomarkers and pharmacogenetics, this table only includes general side effects of the included drugs. Thus, the existing FDA table offers limited information on genetic variations that may increase drug side effects. Aims: The purpose of this paper is to provide a web-based pharmacogenomics search tool composed of a comprehensive list of medications that have pharmacogenetic relevance to perioperative medicine that might also have application in other fields of medicine. Method: For this investigation, the FDA table of pharmacogenomics biomarkers in drug labeling was utilized as an in-depth of drugs to construct our pharmacogenetics drug table. We performed a literature search for drug–gene interactions using the unique list of drugs in the FDA table. Publications containing the drug–gene interactions were identified and reviewed. Additional drugs and extracted gene-interactions in the identified publications were added to the constructed drug table. Result: Our tool provides a comprehensive pharmacogenetic drug table including 258 drugs with a total of 461 drug–gene interactions and their corresponding gene variations that might cause modifications in drug efficacy, pharmacokinetics, pharmacodynamics and adverse reactions. This tool is freely accessible online and can be applied as a web-based search instrument for drug–gene interactions in different fields of medicine, including perioperative medicine. Conclusion: In this research, we collected drug–gene interactions in a web-based searchable tool that could be used by physicians to expand their field knowledge in pharmacogenetics and facilitate their clinical decision making. This precision medicine tool could further serve in establishing a comprehensive perioperative pharmacogenomics database that also includes different fields of medicine that could influence the outcome of perioperative medicine.

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Section: Resultsmentioning

confidence: 99%

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

Zarei

Costas

Orozco

et al. 2020

JPM

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“…Тому останнього часу активно вивчають роль генетичної мінливості у особливостях реакції на медикаментозну терапію. Зокрема, доведено, що з фармакогенетикою периопераційних ЛЗ пов'язані такі ускладнення загальної анестезії, як злоякісна гіпертермія, післяопераційна нудота і блювання, уповільнене відновлення після анестезії [5].…”

Section: результати та їх обговоренняunclassified

PHARMACOGENETIC ASPECTS OF THE USE OF PERIOPERATIVE DRUGS IN PEDIATRICS. Review

Кhaitovych

Kysil²,

Zhovnir³

2022

Med. Sci. of Ukr.

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Relevance. It is known that in children the frequency of perioperative critical events due to the introduction of drugs is more than 5%. For example fentanyl, which is used as an adjunct to surgical anesthesia, is a major factor in increasing the number of deaths from opioid overdoses. Among the areas of reducing the frequency of severe adverse reactions to perioperative drugs - taking into account the pharmacogenetic variations of the patient. Objective is to consider current data on pharmacogenetic aspects of pharmacokinetics and pharmacodynamics of perioperative drugs. Methods. Analysis of the data presented in PubMed by keywords "pharmacogenetics", "general anesthetics", "analgesics", "muscle relaxants", "children". Search depth – 7 years (2014-2020), with a retrospective deepening of some positions until 2002. Results. The pharmacogenetic aspects of the pharmacokinetics of perioperative drugs are related to the genes of the enzymes that metabolize them and their transporters. Current data on the prevalence of polymorphic alleles of CYP2C9 genes (provides metabolism of nonsteroidal anti-inflammatory and anticonvulsant drugs) and CYP2D6 (metabolizes opioids, antidepressants, antiemetics) in Europe and, in particular, in Ukraine were presented. Thus, the inactive allele CYP2C19 * 2 was found in 13%, while the allele of increased activity CYP2C19 * 17 - in 25% of the population of Ukraine; allele with lost CYP2D6 function (CYP2D6 * 4) - in 18.6% of Ukrainians. Homozygotes with CYP2C9 * 3 polymorphism metabolize nonsteroidal anti-inflammatory drugs much more slowly than wild-type carriers, which may lead to their accumulation and side effects. The analgesic effect of codeine occurs only after it is metabolized in the liver by CYP2D6 to morphine. Respiratory depression, apnea and death may occur in patients with excessive metabolic rate even after a single dose of codeine; however, was noted the ineffectiveness of ondansetron due to a decrease in its concentration in the blood in thesepatients. Concomitant use of midazolam and fentanyl may prolong the effect of fentanyl by competing metabolism of midazolam by the hepatic enzyme CYP3A4, especially in patients with low metabolism. Plasma butyrylcholinesterase deficiency reduces succinylcholine inactivation in 1 in 1,500 people. Changing the genotype of uridine diphosphate glycosyltransferase causes increased glucuronidation of morphine, which may lead to a decrease in its effectiveness. As an example of pharmacogenetic changes in pharmacodynamics can be considered malignant hyperthermia, which occurs due to exposure to volatile anesthetics and depolarizing muscle relaxants in mutations in the RYR1 gene. Carriers of the minor allele (G) of the 5HT2A rs6313 gene require less propofol and 40% less time to start induction of anesthesia. Conclusions. The efficacy and safety of perioperative drugs are largely related to the pharmacogenetic aspects of their pharmacokinetics, especially mutations in genes of enzymes of the metabolism. Mutations in the genes of volatile anesthetic receptors and depolarizing muscle relaxants when their used cause a risk of malignant hyperthermia. The application of pharmacogenetics is the need to titrate drugs that have significant variability of action depending on the genotype. It is advisable to avoid the use of drugs with a high risk of pharmacogenetic reactions, if other alternative drugs are available.

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“…10 However, the application of pharmacogenomics in anesthetics is currently limited. 11 Therefore, exploring potential SNPs associated with propofol susceptibility is necessary to achieve precision and personalized medicine during the perioperative period.…”

Section: Introductionmentioning

confidence: 99%

GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility

Zeng

Cao

Chen

et al. 2022

PGPM

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To explore the effect of gene polymorphisms of propofol GABA A receptor and metabolic enzyme on drug susceptibility during the induction period of general anesthesia. Patients and Methods: A total of 294 female patients aged 18-55 years, ASA I-II, who underwent hysteroscopy with intravenous general anesthesia, were included in the study. Anesthesia was induced by continuous intravenous infusion of propofol at 40 mg•kg −1 •h −1 . Infusion of propofol was ended when both the Modified Observer's Assessment of Awareness/Sedation scale (MOAA/S scale) decreased to 1 and the BIS index decreased to 60. The time when the MOAA/S scale decreased to 1 and the time when BIS index decreased to 60 was recorded to assess the susceptibility to the sedation effect. The maximum decreased percentage in mean arterial pressure (MAP) within 5 minutes was recorded to assess the susceptibility of cardiovascular response. Venous blood of each patient was collected to identify the presence of genetic variants in the GABRA1, GABRA2, GABRB2, GABRB3, GABRG2, CYP2B6, and UGT1A9 genes using the Sequenom MassARRAY ® platform. Results: After receiving propofol infusion, carriers of polymorphic GABRA1 rs4263535 G allele required significantly less time for BIS decreased to 60, while carriers of polymorphic GABRB2 rs3816596 T allele required significantly more time for BIS decreased to 60, carriers of polymorphic GABRA1 rs1157122 C allele and carriers of polymorphic GABRB2 rs76774144 T allele had a significantly less change in MAP. Conclusion: GABRB2 rs3816596 and GABRA1 rs4263535 polymorphisms are associated with susceptibility to the sedation effect of propofol. GABRA1 rs1157122 and GABRB2 rs76774144 polymorphisms are associated with the degree of drop in blood pressure after propofol infusion.

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The pharmacogenetics of Medications Used in General Anesthesia

Cited by 18 publications

References 99 publications

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

A Web-Based Pharmacogenomics Search Tool for Precision Medicine in Perioperative Care

PHARMACOGENETIC ASPECTS OF THE USE OF PERIOPERATIVE DRUGS IN PEDIATRICS. Review

GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility

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