Preview

Rational Pharmacotherapy in Cardiology

Advanced search

Pharmacogenetic Aspects of Postoperative Anesthesia with Ketoprofen in Cardiac Surgery Patients

https://doi.org/10.20996/1819-6446-2021-10-11

Full Text:

Abstract

Aim. Evaluation of the effect of polymorphisms of the CYP2D6, CYP2C8 genes on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Material and methods. The study included 90 patients with an established diagnosis of coronary artery disease and postoperative period after cardiac surgery. Patients received ketoprofen 100 mg intramuscularly 2 times a day for 5 days. The intensity of pain was rated by Numeric Rating Scale. The severity of dyspepsia was assessed by the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. DNA was isolated from venous blood using an automated system. Single nucleotide polymorphisms CYP2C8 (C>T) rs11572080, CYP2D6*4 (1846G>A) rs3892097 were determined by the real-time polymerase chain reaction method.

Results. In patients with genotypes GA and GG for the allelic variant CYP2D6*4, significant differences in the intensity of pain syndrome were found on days 4 and 5 of the postoperative period: 3,91±2,17 and 4,95±1,8 points (p=0,04), 3,52±1,95 and 4,5±1,7 points (p=0,04) in patients with GA and GG genotypes on days 4 and 5, respectively. In patients with the CT genotype for the CYP2C8 rs11572080, the severity of dyspepsia by GSRS was significantly higher than in patients with the CC genotype: 22,67±7,64 and 18,97±4,25 points, respectively.

Conclusion. Patients with the GA genotype for the CYP2D6*4 allelic variant showed a lower intensity of pain syndrome than the GG genotype. In patients with the CT genotype for the CYP2C8 rs11572080, higher dyspepsia was revealed than in the CC genotype.

About the Authors

T. E. Morozova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Tatiana E. Morozova

Moscow, eLibrary SPIN 7917-1951



D. A. Shatsky
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Dmitry A. Shatsky

Moscow



N. V. Shikh
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Nadezhda V. Shikh

Moscow, eLibrary SPIN 4950-7164



E. V. Shikh
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Evgeniya V. Shikh

Moscow, eLibrary SPIN 2397-8414



T. B. Andrushchyshina
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Tatiana B. Andrushchyshina

Moscow, eLibrary SPIN 7738-6523



M. V. Lukina
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Maria V. Lukina

Moscow, eLibrary SPIN 4570-6074



A. A. Kachanova
Russian Medical Academy of Continuing Professional Education
Russian Federation

Anastasia A. Kachanova

Moscow, eLibrary SPIN 1214-8156



Z. A. Sozaeva
Russian Medical Academy of Continuing Professional Education
Russian Federation

Zhannet A. Sozaeva

Moscow, eLibrary SPIN 4138-4466



G. N. Shuev
Russian Medical Academy of Continuing Professional Education
Russian Federation

Grigorii N. Shuev

Moscow, eLibrary SPIN 4172-1330



N. P. Denisenko
Russian Medical Academy of Continuing Professional Education
Russian Federation

Natalia P. Denisenko

Moscow, eLibrary SPIN 5883-6249



E. А. Grishina
Russian Medical Academy of Continuing Professional Education
Russian Federation

Elena A. Grishina

Moscow, eLibrary SPIN 3357-3591



D. A. Sychev
Russian Medical Academy of Continuing Professional Education
Russian Federation

Dmitry A. Sychev

Moscow, eLibrary SPIN 4525-7556



References

1. Guimarães-Pereira L, Reis P, Abelha F, et al. Persistent postoperative pain after cardiac surgery: a systematic review with meta-analysis regarding incidence and pain intensity. Pain. 2017;158(10):1869-85. FDOI:10.1097/j.pain.0000000000000997

2. Guimarães-Pereira L, Farinha F, Azevedo L, et al. Persistent Postoperative Pain after Cardiac Surgery: Incidence, Characterization, Associated Factors and its impact in Quality of Life. Eur J Pain. 2016;20(9):1433-42. DOI:10.1002/ejp.866.

3. Ovechkin AM, Bayalieva AZ, Ezhevskaya AA, et al. Postoperative analgesia. Annals of Critical Care. 2019;(4):9-33 (In Russ). DOI: 10.21320/1818-474X-2019-4-9-33.

4. Sousa-Uva M, Head SJ, Milojevic M, et al. 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery. Eur J Cardiothorac Surg. 2018;53(1):5-33. DOI:10.1093/ejcts/ezx314.

5. Zafar F, Shoaib MH, Yousuf RI, et al. Pharmacokinetic and bioequivalence studies of fast dispersible ketoprofen tablets in healthy volunteers. Pak J Pharm Sci. 2017;30(4):1239-44.

6. Instructions for the medical use of the drug Ketonal, solution for intravenous and intramuscular administration of 50 mg/ml, 2 ml ampoules [cited 02/20/2021]. Available from: (In Russ.)

7. Manikandan P, Nagini S. Cytochrome P450 Structure, Function and Clinical Significance: A Review. Curr Drug Targets. 2018;19(1):38-54. DOI:10.2174/1389450118666170125144557.

8. Theken KN, Lee CR, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clin Pharmacol Ther. 2020;108(2):191-200. DOI:10.1002/cpt.1830.

9. Tornio A, Backman JT. Cytochrome P450 in Pharmacogenetics: An Update. Adv Pharmacol. 2018;83:3-32. DOI:10.1016/bs.apha.2018.04.007.

10. Lazarska KE, Dekker SJ, Vermeulen NP, Commandeur JN. Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism. Toxicol Lett. 2018;284:70-8. DOI:10.1016/j.toxlet.2017.11.038.

11. Hou X, Zhou J, Yu S, et al. Differences in the In Vivo and In Vitro Metabolism of Imrecoxib in Humans: Formation of the Rate-Limiting Aldehyde Intermediate. Drug Metab Dispos. 2018;46(9):1320-8. DOI:10.1124/dmd.118.081182.

12. Kokki H. Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients. Paediatr Drugs. 2010;12(5):313-29. DOI:10.2165/11534910-000000000-00000.

13. Morozova TE, Shatsky DA, Shikh NV, et al. Evaluation of the Influence of CYP2C9*2, CYP2C9*3 Gene Polymorphisms on the Efficacy and Safety of Postoperative Analgesia with Ketoprofen in Patients after Cardiac Surgery. Rational Pharmacotherapy in Cardiology. 2021;17(4):570-75 (In Russ). DOI:10.20996/1819-6446-2021-08-12.

14. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-57. DOI:10.1016/j.jpain.2015.12.008.

15. Kulich KR, Madisch A, Pacini F, et al. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008;31(6):12. DOI:10.1186/1477-7525-6-12.

16. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):179-84. DOI:10.1159/000339789

17. Namipashaki A, Razaghi-Moghadam Z, Ansari-Pour N. The Essentiality of Reporting Hardy-Weinberg Equilibrium Calculations in Population-Based Genetic Association Studies. Cell J. 2015;17(2):187-92. DOI:10.22074/cellj.2016.3711

18. Zajic SC, Jarvis JP, Zhang P, et al. Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative. Pharmacogenet Genomics. 2019;29(3):49-57. DOI:10.1097/FPC.0000000000000364.

19. Calvo AM, Zupelari-Gonçalves P, Dionísio TJ, et al. Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9. J Pain Res. 2017;10:1581-9. DOI:10.2147/JPR.S138147.

20. Siu YA, Hao MH, Dixit V, Lai WG. Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants. Drug Metab Pharmacokinet. 2018;33(5):219-27. DOI:10.1016/j.dmpk.2018.06.001.


For citation:


Morozova T.E., Shatsky D.A., Shikh N.V., Shikh E.V., Andrushchyshina T.B., Lukina M.V., Kachanova A.A., Sozaeva Z.A., Shuev G.N., Denisenko N.P., Grishina E.А., Sychev D.A. Pharmacogenetic Aspects of Postoperative Anesthesia with Ketoprofen in Cardiac Surgery Patients. Rational Pharmacotherapy in Cardiology. 2021;17(5):719-723. (In Russ.) https://doi.org/10.20996/1819-6446-2021-10-11

Views: 101


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)