Immunomodulators uses and side effects .pptx

Immunomodulators uses adverse effects. organ transplantation treatment and regimen.

1. IMMUNOMODULATORS

2. Immunomodulators Drugs which either Suppress the immune system - Immunosuppressants Stimulate the immune system – Immunostimulants

3. Characteristics of an ideal immunomodulator It Should Stimulate both specific and non specific immune response Act as an adjuvant along with vaccine Active through oral route Compatible with other drugs Short withdrawal period with low tissue residues Inexpensive

4. Should not be Toxic Antigenic Pyrogenic Long side effects in the body

5. Uses Immunodeficiency disorders Chronic infections Cancer Autoimmunity Organ transplantation

6. Immunosuppressants DRUGS Calcineurin inhibitors:– Cyclosporine, Tacrolimus Antiproliferative / antimetabolic : – Sirolimus, Azathioprine, Methotrexate , Cyclophosphamide

7. Immunomodulators Glucocorticoids – Prednisolone Antibodies - Polyclonal antibody:- Antithymocyte Globulin Monoclonal antibody:- Anti-IL-2 Receptor Anti-TNF Reagents

8. Calcineurin Inhibitors Cyclosporine:- Most effective immunosuppressant drugs in routine use Target the intracellular signaling pathway induced by T cell receptor activation Selectively inhibits T lymphocyte proliferation, IL-2 & other cytokine production Given orally or i.v , plasma half life 24 hr Adverse effect: Renal dysfunction, hyperuricemia, nephrotoxicity, hypertension

9. TACROLIMUS More potent than cyclosporine Inhibits T cell activation by inhibiting Calcineurin Binds to intracellular protein Administered orally & i.v Plasma half life is 12hrs Metabolized by CYP3A Tacrolimus + cyclosporine  synergistic nephrotoxicity

10. Antiproliferative & Antimetabolic Drugs Sirolimus:- Inhibits T-cell activation & proliferation Does not affect calcineurin activity Oral bioavailability 15%, Fat meals reduces its bioavailability Plasma half life 62 hr Adverse effect:- increases Serum cholesterol ,Triglycerides Anemia, Fever, Nephrotoxicity Thrombocytopenia, Tumors

11. Azathioprine Purine antimetabolite Prodrug of 6-mercaptopurine Marked effect on T lymphocytes Suppresses cell mediated immunity Side effect:- bone marrow suppression, leukopenia, alopecia

12. Methotrexate Oldest antineoplastic drugs Inhibits dihydrofolate reductase Depresses cytokine production, cellular immunity, anti-inflammatory property Uses: rheumatoid arthritis, myasthenia gravis, uveitis

13. Cyclophosphamide Effect on humoral immunity compared to cell mediated immunity uses:- prevent graft rejection in organ transplant prevent/control autoimmune disorder such as rheumatoid arthritis, psoriasis, Atopic dermatitis, inflammatory bowel disease

14. Glucocorticoids First hormonal agents recognized as having lympholytic properties Anti inflamatory & immunosuppressant effect Cellular immunity is more affected than humoral immunity

15. Antibodies Polyclonal antisera generated by repeated injections of human thymocytes or lymphocytes - animals Serum immunoglobulin is purified Preparations vary in efficacy & toxicity Adverse effect:- Serum sickness, risk of infection Hematologic complications include leukopenia & thrombocytopenia

16. Anti-TNF α antibodies Adalimumab, infliximab Antibodies that bind TNF-  Blocking TNF-  from binding to TNF receptors on inflammatory cell surfaces

17. Immunostimulants Levamisole Thalidomide BCG Recombinant Cytokines Immunization Passive Active

18. Immunostimulants Levamisole Stimulates B, T lymphocytes, macrophages,monocytes Combined with 5-Fluorouracil improves survival of patients suffering from colon cancer

19. Bacillus Calmette Guerin An attenuated live culture of Calmette Guerin strains of Mycobacterium bovis Induces granulomatous reaction at site of administration By unclear mechanism this preparation is active against tumors , carcinoma Adverse effect- hypersensitivity,fever,malaise,chills

20. Recombinant Cytokines Interferons Bind to specific cell-surface receptors that initiate a series of intracellular events: -- Increased phagocytosis by macrophages --Augmentation of specific cytotoxicity by T lymphocytes Uses: hairy cell leukemia , malignant melanoma, follicular lymphoma & AIDS (Kaposi's sarcoma )

21. Immunization Active or passive Active immunization - stimulation with antigen to develop immunologic defense against future exposure Passive immunization - administration of preformed antibodies to an individual who is already exposed or is about to be exposed to antigen.

22. Vaccines Active immunization Administration of antigen Booster doses are often required, especially when killed (inactivated) organisms are used as immunogen

23. Immune Globulin Passive immunization is indicated --when individual is deficient in Abs because of congenital or acquired immunodeficiency -- Protection provided usually lasts from 1 to 3 months Immune globulin is derived from pooled plasma of adults Specific immune globulin preparations are available for hepatitis B, rabies, tetanus, varicella-zoster, cytomegalovirus

24. contd... Rho Immune globulin Prophylaxis against hemolytic disease of newborn due to Rh incompatibility between mother and fetus Binds Rho antigens, thereby preventing sensitization Adverse effects: Injection site discomfort, low-grade fever myalgia, lethargy, anaphylactic shock have been reported.

25. Management of organ transplant rejection I mmunosuppressants are essential for successful organ transplantation. 3 types of regimens are used I . Induction regimen: given in perioperative period: starting just before transplant to about 2-12 weeks after it. --drugs used: cyclosporine/ tacrolimus/ sirolimus + prednisolone + Mycophenolate mofetil/azathioprine 2.Maintenance regimen: given for prolonged periods, may be life-long. -- drugs used cyclosporine/tacrolimus, sirolimus, prednisolone, azathioprine

26. 3. Antirejection regimen: given to suppress an episode of acute rejection. -- drugs used: Steroid pulse therapy (methylprednisolone 0.5- 1 g i.v. daily for 3- 5 days) is effective Adverse effects: increases risk of bacterial, fungal, viral and opportunistic infections also lymphomas & related malignancies