WAYS TO PREVENT SIDE EFFECTS OF NONSTEROIDAL DRUGS

Аннотация

Adverse effects of medications, particularly those affecting the kidneys and cardiovascular system, represent a significant global medical concern. Non-steroidal anti- inflammatory drugs (NSAIDs) are among the primary contributors to these complications, as they are one of the most widely used drug classes. The pharmacological action of NSAIDs involves inhibiting the synthesis of vasodilatory renal prostaglandins by deactivating the cyclooxygenase enzyme. This inhibition can result in vasomotor acute kidney injury, acute tubulointerstitial nephritis, chronic kidney disease, and other renal complications. Kеywоrds: kidneys, nonsteroidal anti-inflammatory drugs, glomerular filtration rate. INTRОDUСTIОN Side effects of various drugs have become a serious medical and social problem today, which is explained by [1]: • their often unjustified prescription, inadequate dosages and unjustified duration of use; • interactions between different classes of drugs; • insufficient understanding of the pharmacodynamic and pharmacokinetic characteristics of drugs; • insufficient knowledge of the features of side effects of different classes of drugs; • lack of proper monitoring of patients during drug therapy; • late diagnosis of side effects that have developed, which makes it difficult to eliminate them and increases the unfavorable prognosis; • an increase in the frequency of hospitalizations and deaths due to side effects of drugs; • high financial costs aimed at eliminating side effects. MАTЕRIАLS АND MЕTHОDS The high frequency (often unjustified) of prescribing NSAIDs and a wide range of side effects (including life-threatening ones), including complications from the gastrointestinal tract (dyspepsia, ulcers, bleeding and perforation of the upper and lower gastrointestinal tract), cardiovascular system (destabilization of blood pressure and heart failure, increased risk of cardiovascular catastrophes), liver and kidneys, confirm the complexity and importance of studying this problem. This review examines the renal and cardiovascular side effects of NSAIDs. Discussion of other complications developing with the use of NSAIDs is not the purpose of our report. RЕSULTS АND DISСUSSIОN Most reports note a relatively low frequency of renal side effects, amounting to 1–4% in individuals taking NSAIDs for a long time. However, due to their widespread use, the frequency of adverse events caused by NSAIDs in the structure of all drugs used is 25% in the USA and 21% in the UK. Serious side effects of NSAIDs requiring hospitalization have a high proportion [2]. L.A. Dudareva and M.M. Batyushin consider the side effects of NSAIDs (including renal ones) as a “national tragedy” [3]. Many studies and their meta-analyses have 44 ` demonstrated a link between the development of acute kidney injury (AKI) and the use of NSAIDs. Thus, C. Huerta, J. Castellsaque et al. [4] studied the risk of developing AKI in 386,916 patients (aged 50–84 years). During the observation period, 103 cases of AKI were diagnosed. In patients receiving NSAIDs, the risk was 3 times higher compared to the control (odds ratio - OR 3.2, 95% confidence interval - CI 1.8–5.8). The increased risk was associated with an increased duration of therapy and high doses of NSAIDs (OR 3.4, 95% CI 1.6–7.0). The meta- analysis presented by P. Ungprasert et al. [2] showed a statistically significant increase in the risk of developing AKI with the use of NSAIDs (OR from 1.58 to 2.11). At the same time, there were no differences between individual representatives of NSAIDs. The risk was somewhat lower, but statistically insignificant (p≥0.19) for cyclooxygenase (COX)-2-selective drugs. NSAIDs inhibit COX, which catalyzes the process of PG synthesis. Under the influence of COX, cyclic endoperoxide PgG2 is formed from arachidonic acid, which is then converted into PgH2 by peroxidation with the simultaneous production of unstable toxic oxygen radicals. PgH2, in turn, is converted into PgE2, PgI2, PgF2 and thromboxane. PG synthesis is activated by vasoactive hormones and cytokines, as well as hypoxia, ischemia and cellular mechanical disorders [4]. The formation and localization of different PGs are determined by the features of the expression of isoenzymes - COX-1 and COX-2. Expression of COX-1 occurs in arteriolar smooth muscle, in mesangial and endothelial cells, parietal epithelial cells of the Shumlyansky-Bowman capsule, in cells of the cortical and medullary collecting ducts. Expression of COX-2 occurs in cells of the macula densa, in epithelial cells of the ascending thick limb of the loop of Henle, as well as in podocytes and arteriolar smooth muscle, in medullary interstitial cells and in cells of the cortical part of the collecting ducts and proximal tubules [1]. NSAIDs (including gels) are the most common cause of vasomotor (hemodynamic) AKI. This complication is caused by blockade of vasodilator PG synthesis, leading to decreased blood flow in afferent arterioles, glomerular