Tehseen Irshad,
Bilal,
Sowby Jan,
- Assistant Professor, St.Soldier Group of Institutions, Jalandhar, Punjab, India
- Anaesthesiologist, Government Medical College (GMC), and Associated Hospital, Baramulla, Jammu & Kashmir, India
- Assistant Professor, St.Soldier Group of Institutions, Jalandhar, Punjab, India
Abstract
Pharmacogenomics studies how a person’s genetic profile affects their reaction to drugs, which is vital in anesthesia. Anesthetic pharmacology depends significantly on drug metabolism, which involves complex biochemical processes that manage the absorption, distribution, metabolism, and excretion (ADME) of anesthetic drugs. The cytochrome P450 (CYP) enzyme family plays a critical role in the metabolism of various anesthetic drugs, with genetic polymorphisms leading to inter-individual variability in drug responses. Specific CYP enzymes, such as CYP2D6, CYP3A4, and CYP2C19 have been identified as key players in the metabolism of anesthetics like opioids, volatile agents, and intravenous anesthetics. Variations in these enzymes can result in poor, intermediate, extensive, or ultra-rapid metabolism, affecting the efficacy and safety of medications. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in genes encoding drug-metabolizing enzymes influence the pharmacokinetics and pharmacodynamics of anesthetic agents. For example, CYP2D6 polymorphisms impact opioid metabolism, affecting pain management and increasing the risk of adverse reactions, such as respiratory depression. Similarly, CYP3A4 variability alters the metabolism of benzodiazepines and other anaesthetics, leading to differences in sedation levels and recovery times. Understanding these genetic differences allows anaesthesiologists to tailor aesthetic regimens, optimizing dosing strategies and minimizing adverse effects. Progress in genetic testing methods, including polymerase chain reaction (PCR), next-generation sequencing (NGS), and microarray analysis, has made it easier to identify genetic variants associated with drug metabolism. Ethical considerations, including informed consent, data privacy, and the prevention of genetic discrimination, are essential when implementing pharmacogenomic testing in clinical practice. Incorporating pharmacogenomics into anesthetic practice offers the potential to enhance patient outcomes through personalized medicine.
Keywords: Pharmacogenomics, Cytochrome P450, Drug Metabolism, Anesthesia, Genetic Polymorphisms.
[This article belongs to Research & Reviews: A Journal of Drug Formulation, Development and Production ]
Tehseen Irshad, Bilal, Sowby Jan. Molecular Mechanisms of Drug Metabolism in Anesthesia: A Pharmacogenomic Perspective. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2025; 12(01):90-95.
Tehseen Irshad, Bilal, Sowby Jan. Molecular Mechanisms of Drug Metabolism in Anesthesia: A Pharmacogenomic Perspective. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2025; 12(01):90-95. Available from: https://journals.stmjournals.com/rrjodfdp/article=2025/view=208569
References
- Johnson JA, Cavallari LH. Warfarin pharmacogenetics. Trends Cardiovasc Med. 2015 Jan;25(1):33-41. doi: 10.1016/j.tcm.2014.09.001.
- Meyer UA. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nat Rev Genet. 2004 Sep;5(9):669-76. doi: 10.1038/nrg1428
- Flockhart, D. A. (2007). Cytochrome P450 Drug Interaction Table. Clinical Pharmacology & Therapeutics, 81(1), 45-49.
- Evans, W. E., & Relling, M. V. (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science, 286(5439), 487-491.
- Gage, B. F., & Lesko, L. J. (2008). Pharmacogenetics and coumarin therapy: ready for prime time? Clinical Pharmacology & Therapeutics, 84(3), 365-369.
- Dunnenberger, H. M., Crews, K. R., Hoffman, J. M., Caudle, K. E., Broeckel, U., Howard, S. C., … & Relling, M. V. (2015). Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annual Review of Pharmacology and Toxicology, 55, 89-106.
- Kitzmiller, J. P., Groen, D. K., Phelps, M. A., Sadee, W., & Gianella-Borradori, A. (2011). Pharmacogenomic testing: relevance in medical practice: why drugs work in some patients but not in others. Cleveland Clinic Journal of Medicine, 78(4), 243-257.
- Phillips, K. A., Veenstra, D. L., Oren, E., Lee, J. K., & Sadee, W. (2001). Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA, 286(18), 2270-2279.
- McLeod, H. L., & Evans, W. E. (2001). Pharmacogenomics: unlocking the human genome for better drug therapy. Annual Review of Pharmacology and Toxicology, 41(1), 101-121.
- Roden, D. M., & George Jr, A. L. (2002). The genetic basis of variability in drug responses. Nature Reviews Drug Discovery, 1(1), 37-44.
- Ginsburg, G. S., & Willard, H. F. (2009). Genomic and personalized medicine: foundations and applications. Translational Research, 154(6), 277-287.
- McCaffery, K., & Holmes-Rovner, M. (2009). Self-reported outcome measures of the shared decision-making process: a systematic review. Medical Decision Making, 30(2), 144-158.
- The International Warfarin Pharmacogenetics Consortium. (2009). Estimation of the warfarin dose with clinical and pharmacogenetic data. New England Journal of Medicine, 360(8), 753-764.
- Swen, J. J., Nijenhuis, M., de Boer, A., Grandia, L., Derijks, H. J., Brouwers, J. R., & de Boer, A. (2011). Pharmacogenetics: from bench to byte—an update of guidelines. Clinical Pharmacology & Therapeutics, 89(5), 662-673.
- Cousins MJ, Mazze RI. Methoxyflurane nephrotoxicity. A study of dose response in man. JAMA. 1973 Sep 24; 225(13):1611-6. doi: 10.1001/jama.225.13.1611
| Volume | 12 |
| Issue | 01 |
| Received | 06/02/2025 |
| Accepted | 08/03/2025 |
| Published | 04/04/2025 |
| Publication Time | 57 Days |
PlumX Metrics