IMMUNOSUPPRESSANTS IN MODERN PHARMACOLOGY: MECHANISMS OF ACTION AND CLINICAL APPLICATION

541 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz IMMUNOSUPPRESSANTS IN MODERN PHARMACOLOGY: MECHANISMS OF ACTION AND CLINICAL APPLICATION Ismatova.Sh.A. Sultanova.R.X. Tashkent Pharmaceutical Institute, Tashkent, Republic of Uzbekistan e-mail:[email protected] (90)-193-01-10 https://doi.org/10.5281/zenodo.17344101 Relevance: The immune system is a complex network of cells and mediators designed to protect the body from pathogens. However, in some cases (organ transplantation, autoimmune and allergic diseases) this protective reaction becomes excessive or directed against one's own tissues, which requires pharmacological correction. Immunosuppressants are a heterogeneous group of drugs that specifically inhibit the immune response. Their introduction revolutionized transplantology and significantly improved the prognosis for many autoimmune pathologies. However, their use is associated with serious side effects, primarily with an increased risk of infections and cancer, which dictates the need to search for new, more selective targets and drugs. Objective:to conduct a systematic review and analysis of current scientific data on the classification, mechanisms of action, main indications for use and side effects of immunosuppressive drugs. Materials and methods: to write this review, we conducted a search and analysis of scientific publications for the last 10 years (2014-2024) published in peer-reviewed domestic and foreign journals. Materials were searched in the electronic databases "PubMed, Google Scholar, CyberLeninka, eLibrary". Results.1) Detailed analysis of the mechanisms of action and evolution of approaches: Ингибиторы Calcineurin inhibitors (IC) (Cyclosporine, Tacrolimus): The mechanism consists in blocking calcineurin, which prevents the activation of the nuclear factor of activated T cells (NFAT) and, as a result, the transcription of interleukin-2 (IL-2) genes. Tacrolimus was shown in metaanalyses to be more effective in preventing acute renal transplant rejection than cyclosporine, but with a comparable risk of nephrotoxicity and a higher incidence of diabetogenic effects; 2) Trends in combination therapy: Current protocols are based on the principle of synergy to reduce the doses and toxicity of each component. Standard triple regimen after transplantation: IR (tacrolimus) + antimetabolite (MMF) + low-dose glucocorticoid. There is a trend towards early reduction or elimination of glucocorticoids and the use of induction therapy with biological agents (for example, basiliximab) to minimize the nephrotoxicity of IC. 3) Safety profile analysis: The main class-effect of all immunosuppressants is a dose-dependent increase in the risk of opportunistic infections (cytomegalovirus, Epstein-Barr virus) and cancer (skin cancer, lymphoproliferative disorders). IC-based regimens carry the greatest risk of nephrotoxicity and cardiovascular complications, while biologics require vigilance for reactivation of tuberculosis and hepatitis B. Conclusions.Modern pharmacotherapy is based on the principles of combined use of drugs with different mechanisms of action to achieve maximum effectiveness while minimizing doses and, accordingly, toxicity. The mainchallenge for long-term treatment with immunosuppressants remains the management of their side effects, which requires careful monitoring of patients and an individual approach to the choice of treatment regimen.