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2. Mishchuk V. V. Efektyvnist mikrohranuliarnoi formy 5-aminosalitsylovoi kysloty v pisliaoperatsiinomu periodi uskladnenoi khvoroby Krona / V.V. Mishchuk // Shpytalna khirurhiia. Zhurnal imeni L. Ya. Kovalchuka. - 2016. - № 4. - S.68-71.
3. Lichtenstein GR. ACG Clinical Guideline: Management of Crohn's Disease in Adults / EV Loftus, KL Isaacs, MD Regueiro, LB Gerson, BE. Sands // Am J Gastroenterol. - 2018. -Apr;113(4). - P. 481-517.
4. Chavez-Álvarez S. Cutaneous manifestations in inflammatory bowel disease / Chavez-Álvarez S., Gómez-Flores M., OcampoCandiani J. //Gac Med Mex. - 2016. - 152(5). - P.622-630.
5. Vavricka S. R. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort / S. R. Vavricka, L.Brun, P. Ballabeni, V. Pittet, et.al. //American Journal of Gastroenterology. - 2011. - 106(1). -P.110-119.
6. Uvarova K. H. Pozakyshkovi proiavy zapalnykh zakhvoriuvan kyshechnyka / K.H. Uvarova
// Aktualni problemy suchasnoi medytsyny. - 2020. -Vypusk 5. - S.63-73.
7. Vavricka S. R. Extraintestinal manifestations of inflammatory bowel disease / S. R. Vavricka, A.Schoepfer, M. Scharl, P.L.Lakatos, et al.// Inflammatory bowel diseases. - 2015. - 21(8). - P.1982-1992.
8. Annese V. A Review of extraintestinal manifestations and complications of inflammatory bowel disease / V. A. Annese //Saudi journal of medicine & medical sciences. - 2019. - 7 (2). - P.66-73.
9. Lankarani K. B. Oral manifestation in inflammatory bowel disease: a review / K. B. Lankarani, G. R. Sivandzadeh, S. Hassanpour //World journal of gastroenterology: WJG. - 2013. - 19 (46). -Pw8571.
10. National Institute for Health and Care Excellence (2019) Crohn's disease: management. NICE guideline [NG129].
УДК 616.342-002-036.1-085.262.1-092
Honcharuk L.M
PhD in Medical Sciences, Associate Professor Department of Internal Medicine Bukovinian State Medical University;
Piddubna A.A.
PhD in Medical Sciences, Associate Professor Department of Clinical Immunology, allergology and endocrinology Bukovinian State Medical University;
Andrushchak M. PhD in Medical Sciences, Associate Professor Bukovinian State Medical University;
Kulchytska V. 6th year student of 20 group Bukovinian State Medical University;
Vilkhovetska V. 6th year student of 20 group Bukovinian State Medical University; DOI: 10.24412/2520-6990-2023-9168-50-52 SOME ASPECTS OF THE PATHOGENESIS OF GASTRODUODENOPATHY ASSOCIATED WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Abstract.
Nonsteroidal anti-inflammatory drugs have a wide spectrum of therapeutic action, uniquely combining antiinflammatory, analgesic, antipyretic and antithrombotic effects, influencing the processes of neogenesis, cell adhesion and apoptosis. That is why NSAIDs are the most widely used drugs in medicine. Every year, 500 million prescriptions for these drugs are written in the world, about 30 million people take them every day, 2/3 ofpatients - without a prescription and medical supervision. NSAID-induced gastroduodenopathy develops when NSAIDs are taken at a dose that inhibits prostaglandin production and increases gastric motility, causing increased mucosal permeability, neutrophil infiltration, and free radical formation, which ultimately leads to gastric damage.
Key words: gastropathies, nonsteroidal anti-inflammatory drugs, pathogenesis
The therapeutic and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are provided by the pathogenetic mechanism of inhibiting the activity of the enzyme cyclooxygenase (COX) in the metabolism of arachidonic acid, as a result of which the synthesis of prostaglandins (PG) decreases. To date, two
isoforms of cyclooxygenase have been identified -COX-1 and COX-2. The COX-1 enzyme is constantly present in the alimentary canal (AC), kidneys, platelets and ensures the synthesis of thromboxane A2, PG E2 and prostacyclin, which have a cytoprotective effect. Under physiological conditions, COX-2 is localized in
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small amounts in the brain and kidneys. In other tissues, it is detected only during a pathological process and induces the synthesis of PGs, which are involved in inflammation, cell proliferation and destruction. During inflammation, the synthesis of leukotrienes, the release of biogenic amines, free radicals, nitrogen monoxide, and others also increases, which determines the development of the early stage of inflammation. The level of COX-2 is regulated by cytokines, growth factors, and tumor-inducing factors [1-3]. In addition, anti-inflammatory and analgesic effects of NSAIDs are associated with suppression of activation and chemotaxis of neu-trophil granulocytes and reduction of production of toxic free radicals in activated neutrophil granulocytes. NSAIDs also inhibit the stimulation of nitric oxide. By inhibiting the synthesis of PG, NSAIDs affect apoptosis and allow the normalization of the life cycle of cells in the focus of inflammation and inhibit the uncontrolled proliferation of tumor cells [4].It is the ability of NSAIDs to suppress the functional activity of COX-2 that provides their therapeutic effect, but at the same time, they also reduce the activity of COX-1, which causes adverse reactions. However, even short-term use of NSAIDs can lead to the development of serious complications, primarily from the AC side. Approximately 20% of all gastric ulcers and 10% of peptic ulcers are associated with the use of NSAIDs, more than half of which are complicated by bleeding and perforation [5]. In the United States, the use of NSAIDs is the cause of 100,000 hospitalizations and 16,000 deaths annually [6]. Features of erosions and ulcers caused by NSAIDs are multiple, asymptomatic or mildly symptomatic course, most often located in the antral part of the stomach, high risk of bleeding, absence of an inflammatory wall around the ulcer, foveolar hyperplasia of the mucous membrane (MM), rapid healing after withdrawal of NSAIDs [7 ]. In 1986, S. Roth proposed the term "NSAID-gastropathy" (NSAID-gastropathy) to define stomach damage due to taking this group of drugs. According to the recommendations of the American Rheumatology Association (2002), a low risk of NSAID-GDP is noted only in patients who do not have any established risk factor for their occurrence. In the presence of one risk factor, the probability of developing NSAIDs-GDP is considered moderate, and in the presence of two different factors - as high. The main risk factors for NSAIDs-GDP are old age and old age, female sex, history of AC disease, Helicobacter pylori infection, concomitant diseases (cardiovascular, renal and hepatic failure, arterial hypertension, diabetes), complex therapy with the use of anticoagulants and antiplatelet agents, combined use of NSAIDs and gluco-corticosteroids, high doses of NSAIDs, simultaneous use of several NSAIDs, long-term prescription (more than 3 months) of NSAIDs, smoking and alcohol abuse. General contraindications for the appointment of NSAIDs are exacerbation of peptic ulcer disease and gastritis, diseases accompanied by a decrease in blood clotting (hemophilia), bleeding, hemocytopenia, allergic reactions to any drug from the group of NSAIDs [8,9].
Two mechanisms of direct and indirect action of NSAIDs are distinguished in the pathogenesis of the
damaging effect on the gastric mucosa and MM of the gastric mucosa. Direct damage to MM AT NSAIDs are caused by weak organic acids that are in non-ionized form in the acidic environment of the stomach, therefore they directly act on the surface epithelium, destroy it, increase the permeability of hydrogen ions and contribute to their excessive retrodiffusion. A few hours after taking NSAIDs, acute damage to the stomach occurs in the form of submucosal bleeding and erosions. Further use of NSAIDs in most cases leads to the healing of surface erosions, which is explained in the literature by the phenomenon of adaptation to the action of drugs. The mediated effect of NSAIDs on MM is ensured by a sharp inhibition of COX-1 activity, as a result of which the activity of PGs, which provide cytoprotec-tion of MM, decreases. Deficiency of PG I2 leads to the deterioration of blood flow in the stomach wall, disruption of the stabilization of mast cell membranes by ly-sosomes, increased production of oxygen radicals and enzymes by neutrophils, and disruption of vascular en-dothelium regulation. A decrease in PG E2 contributes to a decrease in the secretion of bicarbonates and gastric mucus, as a result of which there is an increase in gastric secretion. NSAIDs are also able to switch the metabolism of arachidonic acid from the prostaglandin to the lipoxygenase pathway and promote the synthesis of leukotrienes, which have a toxic effect on AT and induce the development of local inflammation due to the adhesion of neutrophils to the endothelium [10,11]. Inhibition of COX-1 also disrupts platelet aggregation, which explains the increased risk of gastrointestinal bleeding [12].
Symptoms of NSAID gastropathy are well known to doctors of all specialties. This is a pain that is more often localized in the epigastric area, associated with taking the drug (mostly patients switch to taking it after a meal to reduce unpleasant sensations), dyspeptic syndrome - a feeling of heaviness after a meal, a feeling of rapid satiety, bloating in the epigastrium, less often nausea, vomiting, pain and dyspeptic syndromes are not characterized by seasonality, unlike "classic" gas-troduodenal ulcer. However, it should not be forgotten that patients may not have pain and dyspeptic symptoms, which could alert, worry patients and indicate a possible adverse side effect of the drugs, which may be related, first of all, to the analgesic effect of NSAIDs. In this case, unfortunately, the first clinical manifestations of drug therapy complications are gastrointestinal bleeding or ulcer breakthrough. When deciding on the appointment of NSAIDs, both the expected benefit from their use and the risk of developing complications should be taken into account. It was noted that erosive-ulcerative lesions, as a rule, occur during the first 1 -3 months from the start of treatment, then the risk decreases somewhat and remains stable during the next several years of treatment. That is why patients who have started taking NSAIDs for the first time need explanations and increased attention from the doctor regarding possible complications and their symptoms for timely diagnosis and treatment. That is why timely prevention and diagnosis of NSAIDs-induced lesions of the mucous membrane of the gastrointestinal area, as
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well as a rational and individual approach to prescribing NSAIDs, are of primary importance. Currently, the search for drugs that will be more gentle on the MM of the gastrointestinal tract and have a lower cardiovascular risk, nephro- and hepatotoxicity, and therefore greater safety, in particular when using them in patients with concomitant pathology, is ongoing. If there is an unavoidable need to prescribe NSAIDs to patients with comorbid conditions, prescribe preventive therapy to prevent complications.
Referenses.
1. Viktorov A.P. Meloksikam - perspektivy sohranyayutsya! / A.P. Viktorov // Terapiya. - 2007. -№7-8. - S.36-38.
2. Dzhus M.B. Zastosuvannya koksibiv - novih specifichnih ingibitoriv ciklooksigenazi-2 u revmatologichnij praktici / M.B. Dzhus // Medicina zaliznichnogo transportu Ukrayini. - 2002. - №2. -S.27-31.
3. Shuba N.M. Patogenetichne obgruntuvannya protizapalnoyi terapiyi revmatichnih zahvoryuvan / N.M. Shuba, V.M. Kovalenko // Ukrayinskij revmatologichnij zhurnal. - 2001. - .№3-4 (5-6). - S.18-22.
4. Nasonov E.L. Nesteroidnye protivovospalitelnye preparaty pri revmaticheskih zabolevaniyah: standart lecheniya / E.L. Nasonov // Rossijskij medicinskij zhurnal. - 2001. - T.9., №7-8. -S.265-270.
5. Shokina K.G. Porivnyannya gastrotoksichnosti suchasnih i perspektivnih NPZZ / K.G. Shokina, O.P. Viktorov // Liki. - 2005. - №3-4. -S.47-53.
6. Upper gastrointestinal bleeding associated with the use of NSAIDs. Newer versus older agents / J.R. Laponte, L. Ibanes, X. Vidal [et al.] // Drug Saf. -2004. - Vol. 27. - P.411-420.
7. Tkach S.M. Sovremennye podhody k profilaktiki i lecheniyu NPVP-gastropatij / S.M. Tkach, M.P. Sereda // Suchasna gastroenterologiya. - 2005. -№3. - S.66-71.
8. Moroz G.Z. Nesteroyidni protizapalni preparati: bezpechne vikoristannya v ambulatornij praktici (lekciya) / G.Z. Moroz // Simejna medicina. -2009. - №2. - S.93-97.
9. Singh G. Vybor ingibitora protonnoj pompy dlya lecheniya i profilaktiki povrezhdenij zheludochno-kishechnogo trakta, vyzvannyh priemom nesteroidnyh protivovospalitelnyh preparatov / G. Singh, G. Triadafilopoulos // Suchasna gastroenterologiya. -2008. - №1 (39). - S.98-104.
10. Puzanova O.G. Gastropatiya, viklikana vzhivannyam nesteroyidnih protizapalnih preparativ: diagnostika, profilaktika, likuvannya / O.G. Puzanova, A.S. Svincickij / Nova medicina. - 2003. - №6. - S.27-30.
11. Suchasnij poglyad na gastropatiyi viklikani nesteroyidnimi protizapalnimi preparatami, celekoksib i stan sekretornoyi funkciyi shlunka / G.V. Dzyak, Yu.M. Stepanov, V.I. Gricenko [ta in.] // Suchasna gastroenterologiya. - 2003. - №1 (11).- S.4-11.
12. Drozdov V.N. Gastropatii, vyzvannye nesteroidnymi protivovospalitelnymi preparatami: patogenez, profilaktika i lechenie / V.N. Drozdov // Consilium medicum. - 2005. - T7, №1. - S.3-6.
