Precision anesthesia and pharmacogenomics: a scoping review of personalized drug response

Abstract

Background: Anesthetic agent selection and dosing have historically relied on empirical models without taking into account inter-individual variability in drug response, leading to adverse drug reactions (ADRs). Precision medicine, specifically leveraging pharmacogenomics (PGx), offers a paradigm shift toward personalized anesthesia, enhancing efficacy and safety.
Methods: This scoping review synthesized literature from 2015 to 2025, using systematic database searches and Artificial Intelligence (AI)-powered tools, to identify the most extensively studied genetic variants impacting the pharmacokinetics and pharmacodynamics of common perioperative medications.
Results: Key genetic variants in metabolic enzymes, transporters, and receptors significantly influence anesthetic outcomes. Examples include Reduced Metabolism/Prolonged Effects: Variations in CYP3A4/5 and POR alter midazolam metabolism, risking prolonged sedation. CYP2B6*6 is associated with decreased clearance of propofol and ketamine. BChE deficiency causes significantly prolonged paralysis with succinylcholine. Altered Efficacy/Increased Dose Requirements: OPRM1 118 A > G (G-allele) carriers show a blunted response to morphine, requiring higher doses. CYP2D6 ultra-rapid metabolizers (UMs) can have reduced efficacy of ondansetron and risk toxicity from pro-drugs like codeine and tramadol. Pathogenic mutations in RYR1 and CACNA1S identify patients susceptible to Malignant Hyperthermia from volatile anesthetics. Drug-Drug Interactions (DDIs): PGx overlaps with chronic medications (e.g., antidepressants, beta-blockers) that inhibit CYP2D6, creating a phenoconversion risk that functionally mimics a Poor Metabolizer (PM) phenotype, drastically altering opioid efficacy.
Conclusions: PGx holds transformative potential for the field of anesthesiology by offering actionable insights for drug selection and dose adjustment to mitigate ADRs and optimize pain control.