Introduction of cyclosporine
Cyclosporine (Cyclosporine A), also known as “cyclosporin” or “cyclosporine”, is an immunosuppressive agent widely used to prevent organ transplant rejection. It inhibits the activity of the immune system by inhibiting the activity of T cells with growth. Cyclosporine was first isolated in 1969 by a scientist from Sandoz Pharmaceuticals in Norway for the first time in a soil sample, Tolypocladium inflatum.
Although most of the peptides are synthesized from ribosomes, cyclosporine has 11 amino acids that are not synthesized by ribosomes and contain a rare D-amino acid in nature.
The mechanism of cyclosporine
The most important role of cyclosporine is to reduce the activity of T cells and T cells produced by the immune response.
Cyclosporine binds to the protein, cyclophilin, in the cytoplasm of lymphocytes (especially T cells). A binding protein containing cyclosporine and cyclophilin inhibits calcineurin (which normally activates the transcription of interleukin 2 (IL-2)). Activated T cell receptors increase intracellular calcium concentration, deactivate calcineurin via calmodulin, and then deactivate to further dephosphorylate activated nuclear T-cell nuclear factor (NFATc) Will enter the T cell nucleus to promote IL-2 and related cytokine transcription. Cyclosporine and cyclophilin binding, can inhibit NFATc dephosphorylation; In addition, cyclosporine will inhibit the production of lymphokines and interleukin release.
Cyclosporine prevents the opening of the mitochondrial permeability transition pore (MPTP), while inhibiting the release of cytochrome c (which is a strong contributor to cell death factor). Although this machine has not been used for clinical use, but for the study of cell death has a significant impact.
Application of cyclosporine in medicine
On January 31, 1972, in a single immunosuppressive trial, Sandoz’s staff found that cyclosporine had an immunosuppressive function. Calne and his colleagues at Cambridge University found that cyclosporine was successfully used for immunosuppression of kidney transplantation; Thomas Starzl, a doctor at the University of Pittsburgh Hospital, found that it could be used for immunosuppression of liver transplantation. Until 1983, cyclosporine was officially used for clinical use.
In addition to immunosuppression for transplantation, it can also be used to treat psoriasis, severe atopic dermatitis, pyoderma gangrenosum, chronic autoimmune urticaria, rheumatoid Arthritis and other related diseases, but usually only for more serious diseases. In the United States often made ophthalmic emulsion treatment of dry eye. There are many studies on cyclosporine for autoimmune diseases, and sometimes cases of animal use, especially in immunomodulatory disorders of hemolytic anemia.
The composition of cyclosporine capsules
The main component of cyclosporine capsules is cyclosporine.Cyclosporine A is a selective immunosuppressive agent, clinically used mainly for organ transplantation and immune pathogenesis mediated disease treatment. In recent years, the application of cyclosporine A treatment of refractory primary glomerular disease has aroused more and more attention.
Cyclosporine A has a direct selective immunosuppressive effect on cellular immunity and has a certain degree of indirect effect on humoral and chronic inflammatory responses. The role of point, at the cellular level is mainly selective inhibition of T lymphocytes, in particular inhibition of helper T lymphocytes (Th cells) to produce interleukin-2 (IL-2) and other cytokines; at the molecular level is mainly Interfere with IL-2 and other cytokine gene transcription.
Pharmacology of cyclosporine capsules
Cyclosporine capsules of the main drug cyclosporine (also known as cyclosporin A) for 11 amino acids composed of cyclic peptide. This product is a potent immunosuppressive agent, reversibly specific role in lymphocytes. Animal experiments show that cyclosporine can prolong the survival time of allogeneic organs (skin, heart, kidney, pancreas, bone marrow, small intestine and lung) transplantation, inhibit cell-mediated immune response (including allogeneic immune response, delayed Skin allergic reactions, experimental allergic encephalomyelitis, Freund’s adjuvant arthritis, graft versus host response, and T-cell-dependent antibody production). This product can still inhibit the synthesis of lymphokines (including Ⅰ L-2) and release, blocking the growth cycle of lymphocytes in the G0 phase and G1 early stage. This product does not inhibit erythropoiesis, does not affect phagocytic cell function. Patients with this product compared with the use of other immunosuppressive patients compared to the low incidence of infection.
Mutation of cyclosporine capsules
Cyclosporine capsules are the most common side effects of hirsutism, tremor, gastrointestinal discomfort, gingival hyperplasia and liver, nephrotoxicity, also seen fatigue, anorexia, limb sensory abnormalities, hypertension, amenorrhea and seizures.
The interaction of cyclosporine capsules
The following drugs can affect the plasma concentration of this product should avoid the combination of drugs, if necessary, should be closely monitored cyclosporine blood concentration and adjust its dose.
Increase cyclosporine blood concentration of drugs: macrolide antibiotics, doxycycline, ketoconazole, oral contraceptives, calcium channel blockers, high-dose methylprednisolone and so on.
Drugs that reduce the concentration of cyclosporine: phenobarbital, phenytoin, analgin, rifampicin, isoniazid, amide imipramine, dinoxycin penicillin, trimethoprim and intravenous sulfonamide Methylpyrimidine and so on.
The contraindication of cyclosporine capsules
1, allergic to cyclosporine.
2, severe liver, kidney damage, uncontrolled high blood pressure, infection and malignant tumors were hanged or used with caution.
Pregnant women and lactating women medication pregnant women and lactating women disabled.