ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 43 of 61
Up
УЖМБС 2018, 3(5): 221–230
https://doi.org/10.26693/jmbs03.05.221
Medicine. Reviews

Pathogenetic Background of NSAIDS Adverse Effects and Peculiarities of the Different Age Groups Patients Application

Zlatkina V. V., Rindenko Т. S.
Abstract

The purpose of this review цфs to highlight the peculiarities of the using NSAIDs by children of different age groups, pregnant women, in different trimesters of pregnancy, elderly patients with cardiovascular disorders, kidney diseases to minimize and prevent serious side effects using of NSAIDs, taking into account the pharmacodynamic properties of the group, as well as the search for alternative ways to improve safety. NSAIDs a large group of drugs that are different in chemical structure, united by a common mechanism of pharmacological action by the cyclooxygenase blocking (COX) and reducing of prostaglandin's (PG) synthesis in the focus of inflammation or tissue damage. Pharmacodynamic features of the NSAID group are presented in terms of differences in the mechanism of action (inhibition of COX-1, COX-2). Adverse effects in the COX inhibitors appointment are largely due to an increase in leukotrienes synthesis. In this case takes place the synthesis of products of the predomination of the lipoxygenase pathway of arachidonic acid conversion. The study clarifies the most common side effects causes, such as gastrointestinal disorders, the occurrence of cardiovascular system complications, such as myocardial infarction, ischemic strokes and others. Particular attention should be paid to the appointment of NSAIDs to patients of different age groups, especially children and the elderly. The causes of negative side effects of NSAIDs in a group of children of the neonatal period, and the elder have been thoroughly disassembled. In fact, the most important factor in newborns is their rapid development of physiology. Some of these adverse reactions may be explained by the pharmacokinetics of development (for example, the competitive binding of albumin to bilirubin, the insufficient ability of alcohol dehydrogenase), while others relate to the pharmacodynamics of development (for example, oxygen toxicity on the retina and alveolar microvascular structures, neurons apoptosis after exposure of dexamethasone). The dosing regimen of these drugs are described from the viewpoint of safety for each age period. An in-depth analysis of NSAIDs using during of various trimesters of pregnancy, the most likely side effects, and the basic rules of treatment for this group of drugs are provided. The most frequent were violations that included reduction of limbs, changes in the structure of the amniotic wall, eye defects, oral cavity, pulmonary artery valve stenosis, and defects in the neural tube. However, scientists suggest being very careful when using NSAIDs by pregnant women in the first trimester of pregnancy notwithstanding the fact that there is an instruction on the frequency of using these drugs during pregnancy. If possible, pregnant women are advised to avoid or limit the use of these drugs in the early and late stages of pregnancy. In addition, the article presents data on the characteristics of NSAIDs in elderly patients, taking into account the concomitant diseases and the basic functioning indicators, which can affect on the pharmacokinetics and pharmacodynamics of medications, such as glomerular filtration rate and others. Taking into account the data received by scientists from all over the world, analyzing the results of randomized clinical trials, leading scientists developed the basic points for the prevention of complications associated with the intake of NSAIDs and published in 2015 as clinical recommendations "Rational application of NSAIDs in clinical practice", which should be considered by each doctor who prescribes the drugs of this group in their clinical practice. It is highlighted that the using NSAIDs by children and women during pregnancy should be carried out with a very careful weighting of all possible consequences, without exceeding the dosage regimens, and only those drugs that are allowed in one or another age group, or a trimester of pregnancy, and as short as possible. The use of NSAIDs in low therapeutic doses is almost safe for adult patients with the absence of kidney and cardiovascular diseases. There is a need for monitoring patients taking NSAIDs with associated diseases of the gastrointestinal tract, kidneys, heart, and the appointment of drugs protecting the gastrointestinal mucosa according to existing clinical recommendations. Pharmacogenetic analysis should be implemented to improve the care of patients receiving NSAIDs in order to avoid serious side effects such as renal, cardiovascular and gastrointestinal effects.

Keywords: nonsteroidal anti-inflammatory drugs, NSAIDS, side effects, pregnant women, children, elderly people, COX

Full text: PDF (Ukr) 253K

References
  1. Available from: :https://www.mdedge.com/obgynnews/article/52546/obstetrics/pregnancy-and-nsaids/page/0/1 [digital resource]
  2. Available from: https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug [digital resource]
  3. Available from: https://www.rmj.ru/articles/obshchiestati/Kardiovaskulyarnye_osloghneniya_ingibitorov_COG2_voprosov_bolyshe_chem_otvetov/ [digital resource]
  4. Allegaert K, van den Anker JN. Adverse drug reactions in neonates and infants: a population-tailored approach is needed. British Journal of Clinical Pharmacology. 2015; 80 (4): 788-95. https://doi.org/10.1111/bcp.12430
  5. Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, Bolognese JA, Oxenius B, et al. Randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology. 2006; 131 (6): 1674-82. https://www.ncbi.nlm.nih.gov/pubmed/17087947. https://doi.org/10.1053/j.gastro.2006.08.079
  6. Camille Roubille, Johanne Martel-Pelletier, Jean-Marc Davy, Boulos Haraoui, Jean-Pierre Pelletier. Cardiovascular Adverse Effects of Anti-Inflammatory Drugs. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 2013; 12: 55-67. https://doi.org/10.2174/1871523011312010008
  7. Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006; 368 (9549): 1771-81. https://www.ncbi.nlm.nih.gov/pubmed/17113426. https://doi.org/10.1016/S0140-6736(06)69666-9
  8. Abduyev FM, Bychkova OY, Bondarenko IO, et al. Clinical pharmacology: Textbook for students and doctors. Eds: Yabluchansky MI, Savchenko VM. Kh: VN Karazin KhNU, 2011. 405 p. [Russian]
  9. Goy J, Paikin J, Crowther M. Rofecoxib does not appear to increase the risk of venous thromboembolism: A systematic review of the literature. Thromb Res. 2014; 134 (5): 997-1003. https://doi.org/10.1016/j.thromres.2014.08.030
  10. Graham DJ, Campen, D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005; 365 (9458): 475-81. https://www.ncbi.nlm.nih.gov/pubmed/15705456. https://doi.org/10.1016/S0140-6736(05)17864-7
  11. Gurwitz JH, Avorn J, Bohn RL, Glynn RJ, Monane M, Mogun H. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA. 1994; 272 (10): 781-6. PMID: 8078142
  12. Hernandez RK, Werler MM, Romitti P, Sun L, Anderka M; National Birth Defects Prevention Study. Nonsteroidal antiinflammatory drug use among women and the risk of birth defects. Am J Obstet Gynecol. 2012; 206: 228.e1-8. https://www.ncbi.nlm.nih.gov/pubmed/22196851. https://www.ncbi.nlm.nih.gov/pmc/articles/5893141. https://doi.org/10.1016/j.ajog.2011.11.019
  13. Karateyev AY, Nasonov YL, Yakhno NN. Clinical recommendations "Rational use of non-steroidal anti-inflammatory drugs (NSAIDs) in clinical practice". Sovremennaya revmatologiya. 2015; 1: 4-23. DOI: https://doi.org/10.14412/1996-7012-2015-1-4-23. [Russian]
  14. Kursov SV, Nikonov VV. Cycloooxygenase: physiological effects, actions of inhibitors and the perspectives of the further use of paracetamol (analytical review). Meditsina neotlozhnykh sostoyaniy. 2016; 5 (76): 27-35. [Russian]
  15. Konstam MA, Weir M, Reicin А, Shapiro D, Sperling RS, Barr E, Gertz BJ. Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. Circulation. 2001; 104 (19): 2280-8. https://www.ncbi.nlm.nih.gov/pubmed/11696466
  16. Markova IV, Shabalov NP. Clinical pharmacology of newborns. M: Medicinа, 1984, 288 s. [Russian]
  17. Nasonov YL. The use of nonsteroidal anti-inflammatory drugs and inhibitors of cyclooxygenase-2 at the beginning of the XXI century. Russkiy Meditsinskiy Zhurnal. 2003; 11 (7): 375–8. [Russian]
  18. Chandrasekharan NV, Dai Hu, Roos KLT, Evanson NK, Tomsik J, Elton TS, Simmons DL. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proc Natl Acad Sci. 2002; 99 (21): 13926-31. https://www.ncbi.nlm.nih.gov/pubmed/12242329. https://www.ncbi.nlm.nih.gov/pmc/articles/129799. https://doi.org/10.1073/pnas.162468699
  19. Heleniak Z, Cieplińska M, Szychliński T, Rychter D, Jagodzińska K, Kłos A, Kuźmiuk I, Tylicka MJ, Tylicki L, Rutkowski B, Dębska-Ślizień A. Nonsteroidal anti-inflammatory drugs and chronic kidney disease. J Nephrol. 2017; 30(6): 781–6. https://www.ncbi.nlm.nih.gov/pubmed/27679400. https://www.ncbi.nlm.nih.gov/pmc/articles/5698389. https://doi.org/10.1007/s40620-016-0352-z
  20. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in eldery parients: an underrecognized public health problem. Arch Intern Med. 2000; 27 (160): 777-84. https://www.ncbi.nlm.nih.gov/pubmed/10737277
  21. Ross JS, Krumholz HM. Bringing Vioxx back to market. BMJ. 2018; 360: k242. https://www.ncbi.nlm.nih.gov/pubmed/29371221
  22. Singh G, Miller JD, Lee FH, Pettitt D, Russell MW. Pevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination survey. Am J Manag Care. 2002; 8 (15): 383–91. https://www.ncbi.nlm.nih.gov/pubmed/12416788
  23. Southey ER, Soares-Weiser K, Kleijnen J. Systematic review and meta-analysis of the clinical safety and tolerability of ibuprofen compared with paracetamol in pediatric pain and fever. Curr Med Res Opin. 2009; 25 (9): 2207–22. https://www.ncbi.nlm.nih.gov/pubmed/19606950. https://doi.org/10.1185/03007990903116255
  24. Studenikin VM, Tursunkhujaeva S. S, Shelkovsky VI. Ibuprofen and its use in pediatrics and pediatric neurology. Vopr prakt pediatrii. 2010; 5 (5): 140-4. [Russian]
  25. Studenikin VM, Tursunkhujaeva SS, Shelkovsky VI. Nonsteroidal anti-inflammatory drugs in pediatric practice. Lechashchiy Vrach. 2011; 11: 82-4. [Russian]
  26. The Register of Drugs of Russia "Encyclopedia of Drugs". The 24th issue. Ch Ed: Vyshkovsky GL. Moscow: Vedanta, 2016. 1176 s. [Russian]
  27. Yiannakopoulou E. Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications. Eur J Clin Pharmacol. 2013; 69 (7): 1369–73. https://www.ncbi.nlm.nih.gov/pubmed/23435614. https://doi.org/10.1007/s00228-013-1477-9
  28. Wang J, Zhao T, Tang S, Zhang S, Lv P, Li J, Cao X. Safety assessment of vitacoxib: 180-day chronic oral toxicity studies. Regul Toxicol Pharmacol. 2018; 95: 244-9. https://www.ncbi.nlm.nih.gov/pubmed/29601910. https://doi.org/10.1016/j.yrtph.2018.03.024
  29. Wyatt JE, Pettit WL, Harirforoosh S. Pharmacogenetics of non-steroidal anti-inflammatory drugs. Pharmacogenomics J. 2012; 12: 462–7. https://www.ncbi.nlm.nih.gov/pubmed/23044603. https://doi.org/10.1038/tpj.2012.40