#نکات_طلایی_و_آزمونی_فارماکولوژی 5️⃣1️⃣


📌 مکانیسم عمل داروهای پرتکرار ایمونوفارماکولوژی

📌 CALCINEURIN INHIBITORS: Cyclosporine & Tacrolimus

💊 Cyclosporine
Cyclosporine (cyclosporin A, CSA) is an immunosuppressive agent with efficacy in human organ transplantation, in the treatment of graft-versus-host (GVH) disease after hematopoietic stem cell transplantation, and in the treatment of selected autoimmune disorders. Cyclosporine is a peptide antibiotic that appears to act at an early stage in the antigen receptor–induced differentiation of T cells and blocks their activation. Cyclosporine binds to cyclophilin, a member of a class of intracellular proteins called immunophilins. Cyclosporine and cyclophilin form a complex that inhibits the cytoplasmic phosphatase, calcineurin, which is necessary for the activation of a T cell– specific transcription factor. This transcription factor, NF-AT, is involved in the synthesis of interleukins (eg, IL-2) by activated T cells. In vitro studies have indicated that cyclosporine inhibits the gene transcription of IL-2, IL-3, IFN-γ, and other factors produced by antigen-stimulated T cells, but it does not block the effect of such factors on primed T cells nor does it block interaction with antigen.

💊 Tacrolimus
Tacrolimus (FK 506) is an immunosuppressant macrolide antibiotic produced by Streptomyces tsukubaensis. It is not chemically related to cyclosporine, but their mechanisms of action are similar. Both drugs bind to cytoplasmic peptidylprolyl isomerases that are abundant in all tissues. While cyclosporine binds to cyclophilin, tacrolimus binds to the immunophilin FK-binding protein (FKBP). Both complexes inhibit calcineurin, which is necessary for the activation of the T cell–specific transcription factor NF-AT.

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📌 PROLIFERATION SIGNAL INHIBITORS: Everolimus, Sirolimus & Tofacitinib

💊 Everolimus & Sirolimus:
A newer class of immunosuppressive agents called proliferationsignal inhibitors (PSIs) includes sirolimus (rapamycin) and its derivative everolimus. The mechanism of action of PSIs differs from that of the calcineurin inhibitors. PSIs bind the circulating immunophilin FK506-binding protein 12, resulting in an active complex that blocks the molecular target of rapamycin (mTOR). The mTOR is a key component of a complex intracellular signaling pathway involved in cellular processes such as cell growth and proliferation, angiogenesis, and metabolism. Thus, blockade of mTOR ultimately can lead to inhibition of interleukin-driven T-cell proliferation. Both everolimus and sirolimus also may inhibit B-cell proliferation and immunoglobulin production.

💊 Tofacitinib:
Tofacitinib (Xeljanz) inhibits JAK enzymes that stimulate hematopoiesis and immune cell function in response to cytokine or growth factor signaling. Tofacitinib reduces circulating NK cells, serum immunoglobulins, and C-reactive protein.


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📌 MYCOPHENOLATE MOFETIL
Mycophenolate mofetil (MMF) is a semisynthetic derivative of mycophenolic acid, isolated from the mold Penicillium glaucus. In vitro, it inhibits T- and B-lymphocyte responses, including mitogen and mixed lymphocyte responses, probably by inhibition of de novo synthesis of purines. Mycophenolate mofetil is hydrolyzed to mycophenolic acid, the active immunosuppressive moiety; it is synthesized and administered as MMF to enhance bioavailability.


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