1 / 34

Drugs affecting immune function

Explore the classification, application, and pharmacological effects of immunomodulating agents like glucocorticoids, calcineurin inhibitors, antimetabolic drugs, and immunostimulants. Learn about their clinical uses and adverse reactions.

sammiet
Download Presentation

Drugs affecting immune function

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs affecting immune function Immunopharmacology

  2. Immunomodulating agents- Classification - • Immunosuppressive agents (immunosuppressants) • Immunopotentiating agents (immunostimulants) • Immunization (prophylaxis) • Vaccines;Immune globulin

  3. Immunosuppressants • 1.Glucocorticoids(糖皮质激素类)： • prednisolone (泼尼松龙) , methylprednisolone (甲泼尼松龙) • 2. Calcineurin inhibitors (钙调磷酸酶抑制剂)： • cyclosporine (CsA, 环孢素),tacrolimus(FK506, 他克莫司) • 3. Antiproliferative and antimetabolic drugs (抗增殖/抗代谢类)： • rapamycin (雷帕霉素, sirolimus 西罗莫司), mycophenolate mofetil (MMF, 霉酚酸酯), azathioprine (Aza, 硫唑嘌呤) , cyclophosphamide (CTX, 环磷酰胺) • 4. Antibodies (抗体类)： • antithymocyte globulin (ATG, 抗胸腺细胞球蛋白) • 5. Active TCM components (中药有效成分)： • tripterygium glycosides(雷公藤总苷)

  4. Immunosuppressants- application - • 1.Organ transplantation therapy • Multi-tiered approaches to immunosuppressive drug therapy • Established rejection:blocking activated T lymphocytes, such as high dose glucocorticoids, polyclonal antilymphocyte antibodies, or muromonab-CD3 mAb • Maintenance immunotherapy:such as calcineurin inhibitors, glucocorticoids and mycophenolate mofetil • Intensive induction and lower-dose maintenance • 2. Autoimmune diseases • Rhumatic arthritis, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, polyarthritis nodosa, nephritic syndrome, etc. • 3. Others hypersensitivity

  5. Immunostimulants • 1. Microbial products: • Bacillus Calmette-Guerin (BCG,卡介苗) • 恶性黑色素瘤、白血病、肺癌 • 2. Immunological products from human or animals: • interferons (干扰素), interleukin-2 (IL-2, 白介素-2) • IFN:毛状细胞白血病、恶性黑色素瘤、对肾细胞癌 • 3. Chemical drugs: • levamisole (左旋咪唑 ) • 降低免疫缺陷的感染发生率、慢性反复细菌感染 • 4. Others: • polysaccharides (多糖类), active TCM components

  6. Immunostimulants- application - • 1. Immunodeficient diseases • 2. Chronic refractoryinfections • 3. Tumors • - Adjuvant therapy -

  7. Immunosuppressants

  8. Cell-mediated and humoral immune responses

  9. Immune responses and the actions of immunomodulating agents

  10. 1. Glucocorticoid drugs Prednisone 泼尼松 Prednisolone 泼尼松龙 H

  11. 1. Glucocorticoid drugs • Effects on immune • Suppressing immunological functions and allergy • a) inhibiting all stages of immune responses • b) inducing apoptosis of T and B lymphocytes • c) inhibiting transcription factor －such asnuclear factor B (NF-B) or activating protein-1 (AP-1)activity

  12. 1. Glucocorticoid drugs One of glucocorticoids’ actions: Inhibition of gene transcription (AP-1 and NFB)

  13. 1. Glucocorticoid drugs • Clinical uses • (1) Autoimmune disorders:reumatic fever, reumatic carditis, rhumatic arthritis, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, polyarthritis nodosa, nephritic syndrome, etc. • (2) Rejection of organ transplantation • (3) Allergic diseases:urticaria, serum sicknss, contact dermatitis, drug allergic reactions, chronic severe asthma, status asthmaticus, angioneurotic edema, etc.

  14. 2. Calcineurin inhibitors 钙调磷酸酶 他克莫司 (FK506) 环孢素

  15. 2. Calcineurin inhibitors • Cyclosporin (cyclosporin A, CsA) • Pharmacological effects • Suppressing T-cell-dependent immune mechanisms. • Inhibiting antigen-triggered signal transduction in T-cells, blunting expression of many cytokines including IL-2, and the expression of antiapoptotic proteins. • Forming a complex with cyclophilin (环孢素受体) , which binds to calcineurin, inhibiting Ca2+-stimulated dephosphorylation of the cytosolic component of NFAT. This prevents NFAT dephosphorylation such that NFAT does not enter the nucleus, gene transcription is not activated, and the T lymphocyte fails to respond to specific antigenic stimulation. • Increasing TGF-β expression, so inhibiting IL-2-stimulated T-cell proliferation and generation of cytotoxic T lymphocytes.

  16. 2. Calcineurin inhibitors • Clinical uses • Organ transplantation(kidney, liver, heart, and other organs) • Autoimmune disorders(systemic lupus erythematosus, rheumatoid arthritis, psoriasis (银屑病), etc.)

  17. 2. Calcineurin inhibitors • Adverse reactions • Renal dysfunction: especially combined with other renal toxic drugs • Hepatic toxicity • CNS toxicity: tremor, convulsion, coma, etc. • Increased risk of neoplasia • Increased susceptibility to infections • Others: hirsutism, hypertension, hyperlipidemia, and gum hyperplasia , etc.

  18. 2. Calcineurin inhibitors • Tacrolimus (FK506) • Binding to FKBP (FK506-binding protein) • Used in organ transplantation • CNS, renal, reproductive toxicities

  19. 3. Antiproliferative and antimetabolic drugs 霉酚酸酯 西罗莫司

  20. 3. Antiproliferative and antimetabolic drugs • Rapamycin (Rapa, sirolimus) • Pharmacological effects • Inhibiting T-cell activation and proliferation downstream of the IL-2 and other T-cell growth factor receptors • It binds to and inhibits a protein kinase, designated mammalian target of rapamycin (mTOR), which is a key enzyme in cell-cycle progression

  21. 3. Antiproliferative and antimetabolic drugs • Clinical uses • prophylaxis of organ transplant rejection in combination with a calcineurin inhibitor and glucocorticoids

  22. 3. Antiproliferative and antimetabolic drugs • Adverse reactions • Gastrointestinal effects • Other adverse effects:anemia, leukopenia, thrombocytopenia, hypokalemia or hyperkalemia, fever. Delayed wound healing may occur with sirolimus use.

  23. 3. Antiproliferative and antimetabolic drugs • Mycophenolate mofetil (霉酚酸酯，MMF) • A prodrug of mycophenolic acid (MPA) • Pharmacological effects • a selective, noncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH, 次黄嘌呤单核苷磷酸脱氢酶) , which is an important enzyme in the de novo pathway of guanine nucleotide (鸟嘌呤苷酸) synthesis and B and T lymphocytes are highly dependent on this pathway for cell proliferation

  24. 3. Antiproliferative and antimetabolic drugs • Clinical uses • Prophylaxis of transplant rejection, and it typically is used in combination with glucocorticoids and a calcineurin inhibitor, but not with azathioprine • Systemic lupus erythematosus, rheumatoid arthritis, psoriasis (银屑病) , etc.

  25. 3. Antiproliferative and antimetabolic drugs • Adverse reactions • Gastrointestinal and hematologic toxicitiesincluding diarrhea, vomiting and leukopenia

  26. 3. Antiproliferative and antimetabolic drugs • Azathioprine (Aza)

  27. 3. Antiproliferative and antimetabolic drugs Phamacological effects • Interfering purine nucleotide synthesis in lymphocytes. • Azathioprine appears to be a more potent immunosuppressive agent than 6-mercaptopurine, which may reflect differences in drug uptake or pharmacokinetic differences in the resulting metabolites.

  28. 3. Antiproliferative and antimetabolic drugs • Clinical uses • Organ transplantation, systemic lupus erythematosus, rheumatoid arthritis, etc.

  29. 3. Antiproliferative and antimetabolic drugs • Adverse reactions • Bone marrow suppression, including leukopenia (common), thrombocytopenia (less common), and/or anemia (uncommon) bone marrow suppression, including leukopenia (common), thrombocytopenia (less common), and/or anemia (uncommon) • Increased susceptibility to infections(especially varicella and herpes simplex viruses), • Hepatotoxicity, alopecia, GI toxicity, pancreatitis, and increased risk of neoplasia

  30. 4. Antibodies • Antithymocyte globulin (抗胸腺细胞球蛋白) • Inducing immunosuppression:renal transplant patients with delayed graft function to avoid early treatment with the nephrotoxic calcineurin inhibitors and thereby aid in recovery from ischemic reperfusion injury. • Also used for acute rejection of other types of organ transplants and for prophylaxis of rejection. • Inducing allergic reactions, including fever and chills with the potential for hypotension. including fever and chills with the potential for hypotension.

  31. 4. Antibodies • Muromonab-CD3 (OKT3, 莫罗单抗-CD3, • anti-CD3 monoclonal antibodies ) • Binding to the εchain of CD3, a monomorphic component of the T-cell receptor complex involved in antigen recognition, cell signaling, and proliferation • Acute organ transplant rejection • “Cytokine release syndrome":high fever, chills/rigor, headache, tremor, nausea/vomiting, diarrhea, abdominal pain, malaise, myalgias, arthralgias, and generalized weakness.

More Related