Pharmacogenomics of commonly used intravenous anesthetics.
📄 Abstract
Pharmacogenomics (PGx) is a scientific field that aims to understand how an individual's genetic code regulates drug metabolism and response. The response to many anesthetic drugs varies widely among patients due to many factors including, but not limited to, age, gender, and comorbidities. However, PGx contributes to this variability, particularly regarding adverse drug reactions. This review explores the influence of PGx on five commonly used induction agents in anesthesia: propofol, midazolam, ketamine, etomidate, and thiopental. Propofol metabolism is significantly affected by polymorphisms in CYP2B6, CYP2C9, and UGT1A9, influencing both efficacy and toxicity. Midazolam's PGx is mainly mediated by variations in CYP3A4, CYP3A5, and UDP-glucuronosyltransferase enzymes, with implications for sedation depth and drug clearance. Ketamine response is modulated by polymorphisms in metabolic enzymes (e.g. CYP2B6), as well as neurobiological targets such as brain-derived neurotrophic factor and gamma-aminobutyric acid (GABA) receptors, particularly in psychiatric applications. Etomidate shows less studied but emerging PGx associations, including single-nucleotide polymorphisms in GABA receptor subunits and metabolic enzymes, which may affect both sedative depth and cardiovascular stability. Thiopental is a rapid-acting metabolite whose effect stems from GABA-A receptor potentiation; no studies have yet identified specific genetic polymorphisms influencing its action. Overall, PGx provides a promising avenue for tailoring anesthetic management to improve patient safety and outcomes. However, clinical integration remains limited due to practical and infrastructural barriers. This review highlights the potential and current limitations of pharmacogenomic-guided anesthesia, underscoring its relevance in the era of precision medicine.