RISK MANAGEMENT OF USE DRUGS WITH NARROW THERAPEUTIC INDEX IN CLINICAL PRACTICE. Review
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Keywords

drugs, narrow therapeutic index

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Khaitovych, M. (2019). RISK MANAGEMENT OF USE DRUGS WITH NARROW THERAPEUTIC INDEX IN CLINICAL PRACTICE. Review. Medical Science of Ukraine (MSU), 15(3-4), 105-111. https://doi.org/10.32345/2664-4738.3-4.2019.16

Abstract

Relevance. Today, the pharmacotherapy of many diseases is significantly expanded. However, the amount of pathological conditions associated with the use of drugs has increased. Drug related problems in some cases can be fatal and increase health care costs. It is necessary to be able to anticipate in advance the possibility of developing such conditions, to prevent them. Therefore, the analysis of the causes and mechanisms of development of these conditions is relevant.

Objective. To find out the most common causes of drug related problems and consider the mechanisms of such states.

Methods. Analysis of scientific publications in PubMed by keywords for the period 2001-2018.

Results. The therapeutic index is the ratio of the dose that causes toxic effects in 50% of patients to the dose that causes the expected therapeutic effect in 50% of patients. The therapeutic index ≤ 3 is an indicator that defines drugs with narrow (small) therapeutic index. These drugs include insulin, digoxin, warfarin, levothyroxine, aminoglycoside antibiotics, carbamazepine, lithium, phenytoin, etc.

The risks associated with these drugs are: the use of generic drugs with insufficient bioequivalence, pharmacokinetic interaction and polymorphism of genes of drug metabolism. The main mechanisms of their pharmacokinetic interaction at the stages of absorption (alteration of digestive tract motility, influence on the activity of P-glycoprotein), distribution (competition for blood plasma proteins and tissue proteins), and biotransformation (inhibition or induction of metabolism). The role of polymorphism of genes encoding the activity of isoenzymes cytochrome P450 2C9 and 1A2 and glycoprotein P in the development of adverse drug reactions of drugs with a narrow therapeutic index is presented.

Conclusion. Risk management of using drugs with a narrow therapeutic index should include therapeutic drug monitoring of especially generic drugs, assessment of the risks of pharmacokinetic interaction, widespread introduction pharmacogenetic tests for determine the polymorphism of the genes of metabolism enzymes and drug transporters in the clinical practice.

https://doi.org/10.32345/2664-4738.3-4.2019.16
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References

1. Zatolochina K.E., Pasternak E.Yu., Alyautdin R.N., Snegireva I.I., Romanov B.K., Polivanov V.A., Olefir Yu.V. The problem of interchangeability of drugs with a narrow therapeutic range // Chemical and Pharmaceutical Journal. 2017; 51(8): 51-4. [in Russian]. URL: http://chem.folium.ru/index.php/chem/article/view/4013.
2. Zyiryanov S.K., Fitilev S.B., Shkrebneva I.I., Vozzhaev A.V. Drug interchangeability – clinical efficacy, safety // Neurology, neuropsychiatry, psychosomatics. 2017; 1: 4-10. [in Russian]. URL: https://cyberleninka.ru/article/n/vzaimozamenyaemost-preparatov-klinicheskaya-effektivnost-bezopasnost
3. Mazur I.P., Khaitovych M.V., Holopykho L.I. Clinical pharmacology and pharmacotherapy in dentistry. – 2018, K.: VSV "Medicine". 376 p. [in Ukrainian]. URL: https://www.medpublish.com.ua/klinichna-pharmakologija-ta-pharmakoterapija-v-stomatologiyi-navchalnij-posibnik-vnz-v-r-a-p-mazur-mv-hajtovich-l-golopiho/p-858.html?language=ru
4. Sokolov A.V. Therapeutic drug monitoring // Qualitative Clinical Practice. 2002; 1: 78-88. [in Russian]. URL: https://www.clinvest.ru/jour/article/view/252/260.
5. Khaitovych M.V. Drug transporter glycoprotein-P: clinical relevance // Medical Science of Ukraine. 2016; 12 (1-2): 86-93. [in Ukrainian]. URL: https://msu-journal.com/index.php/journal/article/view/115/100.
6. Adusumilli P., Adepu R, Drug related problems: an over view of various classification systems // Asian J Pharm Clin Res. 2014; 7(4): 7-10. https://innovareacademics.in/journals/index.php/ajpcr/article/view/2728/1122.
7. Abernethy D. R., Woodcock J., Lesko, L. J. Pharmacological mechanism-based drug safety assessment and prediction // Clin. Pharmacol. Ther. 2011; 89 (6), 793-7. https://doi.org/10.1038/clpt.2011.55
8. Baumgartel C., Godman B. Bioequivalence of narrow therapeutic index drugs and immunosuppressives // Genetics a.nd Biosimilars initiative Journal. 2015; 4 (4): 159-160. https://doi.org/10.5639/gabij.2015.0404.035
9. Blix H.S., Viktil K.K., Moger T.A., Reikvam A. Drugs with narrow therapeutic index as indicators in the risk management of hospitalised patients // Pharmacy Practice (Granada). 2010; 8 (1): 50-5. doi: 10.4321/s1886-36552010000100006
10. Bukaveckas L. Adding Pharmacogenetics to the Clinical Laboratory Narrow Therapeutic Index Medications as a Place to Start // Arch Pathol Lab Med. 2004; 128: 1330-3. doi: 10.1043/1543-2165(2004)128<1330:APTTCL>2.0.CO;2
11. Buzoianu A.D., Trifa A.P., Muresanu D.F., Crisan S. Analysis of CYP2C9*2, CYP2C9*3 and VKORC1 -1639 G>A polymorphisms in a population from South-Eastern Europe // J Cell Mol Med. 2012; 16(12): 2919-24. doi: 10.1111/j.1582-4934.2012.01606.x.
12. Carbon M., Correll C.U. Rational use of generic psychotropic drugs // CNS Drugs. 2013; 27 (5): 353-65. https://link.springer.com/article/10.1007/s40263-013-0045-2
13. Desmarais J.E., Beauclair L., Margolese H.C. Switching from brand-name to generic psychotropic medications: a literature review // CNS Neurosci Ther 2011; 17 (6): 750-60. doi: 10.1111/j.1755-5949.2010.00210.x.
14. Ding Y., Yang D., Zhou L., He P., Yao J., Xie P.et al. Cytochrome P450 2C9 (CYP2C9) polymorphisms in Chinese Li population // Int J Clin Exp Med. 2015; 8(11): 21024-33. https://www.ncbi.nlm.nih.gov/pubmed/26885033.
15. Maharani D.D., Syafhan N.F., Hersunaryati Y. Drug-related problems in hospitalized geriatric patients with diabetes mellitus. International Journal of Applied Pharmaceutics. 2018; 10 (1): 142-7. https://doi.org/10.22159/ijap.2018.v10s1.30
16. Goldstein J.A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 2001; 52 (4): 349-55. https://doi.org/10.1046/j.0306-5251.2001.01499.x
17. Elliot D. J., Suharjono S., Lewis B. C., Gillam E.M., Birkett D.J., Gross A.S., Miners J.O. Identification of the human cytochromes P450 catalysing the rate-limiting pathways of gliclazide elimination // British Journal of Clinical Pharmacology. 2007; 64 (4): 450-7. doi: 10.1111/j.1365-2125.2007.02943.x.
18. Ivashchenko D., Rusin I., Sychev D., Grachev A. The Frequency of CYP2C9, VKORC1, and CYP4F2 Polymorphisms in Russian Patients With High Thrombotic Risk Medicina (Kaunas) 2013; 49 (12): 517-21. https://www.ncbi.nlm.nih.gov/pubmed/24858991.
19. Iyer K., Dilipkumar N., Vasaya S.1, Pawar S., Diwan A. Comparison of Drug Related Problems Associated with Use of Narrow Therapeutic Index Drugs and Other Drugs in Hospitalized Patients // Journal of Young Pharmacists. 2018; 10 (3): 318-21. doi:10.5530/jyp.2018.10.70.
20. Johnson J.A. Warfarin pharmacogenetics: a rising tide for its clinical value // Circulation. 2012; 125 (16): 1964-6. doi: 10.1161/CIRCULATIONAHA.112.100628.
21. Koh Y., Kutty F.B., Li S.C. Drug-related problems in hospitalized patients on polypharmacy: the influence of age and gender // Therapeutics and Clinical Risk Management. 2005; 1 (1): 39-48. DOI: 10.2147/tcrm.1.1.39.53597
22. Koonrungsesomboon N., Khatsri R., Wongchompoo P., Teekachunhatean S. The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis // Pharmacogenomics J. 2018; 18 (6): 760-8. doi: 10.1038/s41397-017-0011-3.
23. Lane M.A., Zeringue A., McDonald J.R. Serious Bleeding Events due to Warfarin and Antibiotic Co-Prescription in a Cohort of Veterans // Am J Med 2014; 127 (7): 657-63. doi: 10.1016/j.amjmed.2014.01.044.
24. Li X.X., Yin J., Tang J., Li Y., Yang Q., Xiao Z. et al. Determining the Balance Between Drug Efficacy and Safety by the Network and Biological System Profile of Its Therapeutic Target // Front Pharmacol. 2018; 9: 1245. doi: 10.3389/fphar.2018.01245.
25. Liang B.A., Mackey T.K., Lovett K.M. Illegal "No Prescription" Internet Access to Narrow Therapeutic Index Drugs // Clin Ther. 2013; 35 (5): 694-700. doi: 10.1016/j.clinthera.2013.03.019.
26. Mark T.L., Kassed C., Levit K., Vandivort-Warren R. An analysis of the slowdown in growth of spending for psychiatric drugs, 1986-2008 // Psychiatr Serv. 2012; 63: 13-8. doi: 10.1176/appi.ps.201100564.
27. Meyer J.M., Proctor J., Cummings M.A. et al. Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction // Case Rep Psychiatry. 2016; 2016: 5606098. doi: 10.1155/2016/5606098.
28. Roshanzamiri S., Eslami K., Najmeddin F., Izadpanah M., Hadidi E., Ganji R. Validating a Drug-Related Problems Classification System in Outpatient Setting in Iran // J Res Pharm Pract. 2018; 7 (3): 117-22. doi: 10.4103/jrpp.JRPP_18_17.
29. Ruths S., Viktil K.K., Blix H.S. Classification of drug-related problems // Tidsskr Nor Laegeforen. 2007; 127 (23): 3073-6. https://www.ncbi.nlm.nih.gov/pubmed/18049498.
30. Schwab M., Schaeffeler E., Marx C., Fromm M.F., Kaskas B., Metzler J. et al. Association Between the C3435T MDR1 Gene Polymorphism and Susceptibility for Ulcerative Colitis // Gastroenterology 2003; 124: 26-33. DOI:10.1053/gast.2003.50010.
31. Stasiolek M., Romanowicz H., Polatynska K., Chamielec M. et al. Association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children // Behav Brain Funct. 2016; 12: 21. doi: 10.1186/s12993-016-0106-z.
32. Van der Weide J., Steijns L.S., Van Weelden M.J., De Haan K. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement // Pharmacogenetics 2001; 11: 287-91. DOI:10.1097/00008571-200106000-00002.
33. Yu L.X., Jiang W., Zhang X., Lionberger R., Makhlouf F., Schuirmann D.J. et al. Novel bioequivalence approach for narrow therapeutic index drugs // Clinical Pharmacology and Therapeutics. 2015r; 97 (3): 286-91. doi: 10.1002/cpt.28.
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