Pharmacogenomics and Anesthesia: Is There an Ancestry-Related Response to Anesthetics in Hispanic/Latino Populations?

Background

Individual variability in anesthetic response remains a challenge for surgical safety, perioperative outcomes, and acute pain management. Standard dosing guidelines assume relatively uniform drug metabolism across demographic groups, yet functional variants in cytochrome P450 (CYP450) enzymes alter the pharmacokinetics of opioids, sedatives, and amide local anesthetics. Hispanic/Latino populations carry highly heterogeneous genomes reflecting Indigenous American, European, and African ancestry in continuously varying proportions. Despite being a rapidly growing demographic, they remain markedly underrepresented in pharmacogenomic and perioperative research, and existing genotype-guided dosing guidelines derive largely from European and East Asian cohorts. This review evaluates current evidence on CYP450 variation across Hispanic/Latino subpopulations and its impact on perioperative drug safety, analgesic efficacy, and anesthetic requirements, and asks whether ancestry-related pharmacogenomic differences are clinically meaningful.

Methods

A structured literature search was performed in PubMed/MEDLINE, EMBASE, and SciELO for peer-reviewed studies published 2015–2025. Search terms combined the concepts pharmacogenetics, anesthesia, cytochrome P-450 enzyme system, opioids, and Hispanic or Latino. Clinical trials, observational studies, meta-analyses, and systematic reviews examining genotype–phenotype correlations in perioperative drug metabolism within Hispanic/Latino cohorts were included.

Results

Evidence demonstrates that CYP2D6 allele and phenotype frequencies vary widely across Hispanic/Latino subpopulations according to the proportion of Indigenous American, European, and African ancestry rather than following a single "reference" distribution. Poor-metabolizer frequencies are often lower than in European populations (approximately 2–7% vs 7–10%), reflecting reduced frequency of loss-of-function alleles such as CYP2D6*4, whereas increased-activity gene duplications and African-associated alleles create clinically relevant ultra-rapid and intermediate metabolizer subgroups. This variability produces unpredictable bioactivation of opioid prodrugs such as codeine and tramadol, exposing patients to either therapeutic failure or toxicity, including life-threatening respiratory depression. CYP3A4/CYP3A5 variation, together with drug-transporter (ABCB1) and nuclear-receptor (NR1I2/PXR) polymorphisms, influences midazolam clearance and post-anesthesia recovery, whereas CYP2C19 variation is relevant to diazepam. Evidence that CYP genotype meaningfully alters amide local-anesthetic (e.g., bupivacaine, ropivacaine, lidocaine) block duration in humans remains limited; sodium-channel variants and tissue-level factors are more established contributors.

Conclusion

Ancestry-related genetic variation supports clinically meaningful differences in perioperative drug response across Hispanic/Latino subpopulations, though these reflect an admixture continuum rather than a discrete ethnic category. Because current pharmacogenomic guidelines are built primarily on non-Hispanic cohorts, expanding representation and incorporating pharmacogenomic considerations and targeted screening into pre-anesthetic evaluation are essential steps toward equitable, precision anesthesia care that optimizes analgesia while minimizing preventable adverse drug events in diverse surgical populations.