Pharmacogenetics is the study of how a person’s genes influence their responses to medicinal drugs.1 The origins of pharmacogenetics can be traced back to the geneticist Arno Motulsky, who in 1957 published an article stating that adverse reactions to a particular antimalarial drug and a muscle relaxant are heritable and linked to enzyme deficiencies.1 Since the 1950s, researchers have discovered more gene variants related to numerous drug responses.1 The concept of personalized medicine has also led health professionals to factor genetics into pharmacological treatment.2 Recent studies indicate that pharmacogenetics have an important place in anesthesiology, as genetic differences may affect a patient’s reaction to an anesthetic drug.3 Anesthesiology professionals can use pharmacogenetics throughout the perioperative period to optimize medical treatment for each patient.4 In order to integrate pharmacogenetics into their practice, anesthesia providers will need to understand the basics of pharmacogenetics and its importance to perioperative anesthesiology.
The field of clinical pharmacogenetics integrates biology, pharmacology, genetics and medicine to provide patients with a more individualized experience.2 A patient’s genetics can contribute to medical decisions as do the general health assessment and family medical history.2 While variables such as age and body mass index can affect drug metabolism and reactions, genetics may also play a role. Genetic variants or mutations can affect the enzymes and transporters that control drug metabolism, resulting in highly variable drug reactions in different individuals or for different drug combinations.5 For example, enzymes produced from the group of 60 human cytochrome P450 genes (CYP450) are involved in the formation and metabolism of many intracellular molecules and chemicals.6 CYP450 enzymes are usually found in liver cells, and they metabolize external substances, such as drugs, and internal substances, such as toxins.6 Acetaminophen (i.e., Tylenol) is one of the better-known substances that is metabolized by CYP450 enzymes,7 and the medication’s interaction with alcohol is related to alcohol’s metabolism by the very same enzymes.8 Allele variations in some CYP450 genes, and subsequently the enzymes they code for, have been associated with “poor metabolism” of certain types of drugs.2 Researchers have even identified genetic variations among ethnic and racial groups that cause different reactions to medications.2
Anesthetic drugs are not immune to the rise of pharmacogenetics. Indeed, the field of anesthesiology is a major target for pharmacogenetic research given the narrow dose margins needed for anesthesia induction, the variability of patient responses and the risks of surgery.9 In particular, patients show a wide variety of responses to neuromuscular blockers, opioids, other anesthetic agents and antiemetics.5 A study by Xie et al. demonstrated that variations in two particular genes were significantly associated with time to recovery from general anesthesia.10 Meanwhile, a review by Landau et al. targeted genetic associations with spinal anesthesia-induced hypotension, as well as responses to hypotension and analgesic medications.11 Though they found that genetic variation had modest effects on patient outcomes, they did not notice changes clinical practice.11 Additionally, a review by Aroke and Dungan showed that most anesthetics are metabolized by enzymes in the CYP2 and UGT1 families.12 They also found that the CYP2B6*6 allele is associated with decreased propofol and ketamine metabolism and increased adverse effects, while variants in the UGT1A9 enzyme indicate the need for higher induction dose of propofol.12 Further, opioids are analgesic drugs under particular scrutiny due to high interindividual variability in analgesic and adverse effects.13 Genetic expression can affect patient-to-patient variability via changes in opioid transportation, receptor molecules and metabolizing enzymes.3 Evidently, genetic factors can affect many factors in drug metabolism, thus altering a patient’s need for and reaction to anesthetic drugs.
The rise of pharmacogenetic research shows that genetic factors are crucial to a drug’s metabolism and its effects on the body. This is particularly evident in anesthesiology, where reactions to medications vary widely among individual patients. Genetics can affect interpatient variability in the recovery time, drug clearance and adverse effects associated with many anesthetic medications. In the future, innovative technologies in personalized medicine and bioinformatics will allow improved understanding of pharmacogenetic associations and variations between individuals.5 Anesthesiology professionals should consider integrating pharmacogenetics into their practices in order to improve patient care and reduce complications.4
1. Drew L. Pharmacogenetics: The right drug for you. Nature. 2016;537(7619):S60–S62.
2. Scott SA. Personalizing medicine with clinical pharmacogenetics. Genetics in Medicine. 2011;13(12):987–995.
3. Saba R, Kaye AD, Urman RD. Pharmacogenomics in Anesthesia. Anesthesiology Clinics. 2017;35(2):285–294.
4. Behrooz A. Pharmacogenetics and anaesthetic drugs: Implications for perioperative practice. Annals of Medicine and Surgery. 2015;4(4):470–474.
5. Chan JM. Drug Metabolism and Pharmacogenetics. In: Hemmings HC, Egan TD, eds. Pharmacology and Physiology for Anesthesia (Second Edition). Philadelphia: Elsevier; 2019:70–90.
6. Cytochrome p450. Genetics Home Reference. Bethesda, MD: National Institutes of Health; December 10, 2019.
7. Laine JE, Auriola S, Pasanen M, Juvonen RO. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica. 2009;39(1):11–21.
8. Djordjević D, Nikolić J, Stefanović V. Ethanol interactions with other cytochrome P450 substrates including drugs, xenobiotics, and carcinogens. Pathologie-biologie. 1998;46(10):760–770.
9. Morgan B, Aroke EN, Dungan J. The Role of Pharmacogenomics in Anesthesia Pharmacology. Annual Review of Nursing Research. 2017;35(1):241–256.
10. Xie S, Ma W, Shen M, et al. Clinical and pharmacogenetics associated with recovery time from general anesthesia. Pharmacogenomics. 2018;19(14):1111–1123.
11. Landau R, Smiley R. Pharmacogenetics in obstetric anesthesia. Best Practice & Research Clinical Anaesthesiology. 2017;31(1):23–34.
12. Aroke EN, Dungan JR. Pharmacogenetics of Anesthesia: An Integrative Review. Nursing Research. 2016;65(4):318–330.
13. Kim K. Opioid pharmacogenetics in anesthesia and pain management. International Journal of Anesthesiology & Pain Medicine. 2015;10(2):65–76.