Immunostimulants & immunosuppressants

IT HELPS TO KNOW ABOUT THE KNOWLEDGE REGARDING THE IMMUNOSTIMULANT AND IMMUNOSUPPRESSIVE DRUGS

1. IMMUNOMODULATORS - NIRALI THAKKAR (FROM SMT S.M.SHAH PHARMACY COLLEGE)

2. -These are drugs that suppress the immune response. -Their main therapeutic application is in autoimmune diseases and organ transplantation. IMMUNOSUPPRESSANTS

3. CLASSIFICATION 1.Calcineurin inhibitors: Cyclosporine , Tacrolimus 2.Antiproliferative and cytotoxin agents : Azathioprine , methotrexate,cyclophosphamide 3. mTOR (mammalian target of rapamycin ) inhibitors:Sirolimus 4.Glucocorticoids : Prednisolone , methylprednisolone 5.Biologics : (a)TNF- α inhibitors: Etanercept , Infliximab (b)IL-1 inhibitors: Anakinra (c)Antibodies: Muromonab-CD3 , anti- thymocytes and anti-lymphocyte antibodies

4. MECHANISM OF ACTION

5. 1.CALCINEURIN INHIBITORS - Cyclosporine : Very lipophilic and essentially not soluble in water administered orally , i.v . and i.v . infusion Mechanism of action : enters in target cells ↓ binds to cyclophilin ↓ cyclosporine – cyclophilin complex ↓ inhibit calcineurin and blocks activation of T cells and decresed production of IL-2 and other cytokines

6. 1.CALCINEURIN INHIBITORS Uses : -prevent and treat rejection episodes in organ transplantation like kidney,bone marrow,liver etc -treat autoimmune diseases like myasthenia gravis, rheumatoid arthritis etc.

7. 1.CALCINEURIN INHI BI TORS Adverse effects : - Nephrotoxicity - Hepatotoxicity -Hypertrophy of Gums -Hypertension -Hyperglycemia - Hyperlipidemia -Increased susceptibility to infections -Bone marrow toxicity is minimal

8. 1.CALCINEURIN INHIBITOR Drug Interaction : -Cyclosporine × Aminoglycoside / Amphotericin B/ Vancomycin / NSAIDS: Nephrotoxicity is enhanced -Cyclosporine × Rifampicin / Phenobarbitone / Phenytoin : The blood level of Cyclosporine is reduced due to induction of its metabolism -Cyclosporine × Erythromycin: The plasma level of Cyclosporine is increased as its metabolism is inhibited by erythromycin -Cyclosporine × Potassium sparing diuretics: Severe hyperkalaemia can occur

9. 2. ANTIPROLIFERATIVE AGENTS - Azathioprine : - It is a purine antimetabolite -Incorporation of false nucleotide Mechanism of action : Taken up into the immune cells ↓ Activated to 6-MP ↓ Inhibits purine synthesis ↓ Inhibition of cell Proliferation and impairment of lymphocyte funtion

10. 2. ANTI PROLIFERATIVE AGENTS Uses : -Used in combination with glucocorticoids or cyclosporine for prevention of rejection episodes in organ transplantation -Used in rheumatoid arthritis , Crohn’s disease etc Adverse effects : - Hepatotoxicity -Bone marrow suppresion -Gastrointestinal side effects

11. 3. mTOR Inhibitors Sirolimus : It inhibits T-cell activation and Proliferation. - Mechanism of action: It forms complex with an immunophilin ↓ Inhibits a key enzyme in cell cycle progression ↓ Inhibits the response of interleukin-2 ↓ That blocks activation of T-cells and B-cells

12. 3. mTOR Inhibitors Uses : -To treat and prevent graph rejection reaction Adverse effects : - Myelosuppression -Headache - Hepatotoxicity - Hypokalemia -Risk of infection -Thrombocytopenia

13. 4.GLUCOCORTICOIDS Prednisolone : Induce redistribution of lymphocytes that decrease in peripheral blood lymphocyte count . Mechanism of action : Inhibit proliferation of T-lymphocytes ↓ Decrease expression of interleukines ↓ Blocks the activation of T-cells and B-cells

14. 4.GLUCOCORTICOIDS Uses : -To prevent and treat rejection episodes during organ transplantation. -Autoimmune diseases. Adverse effects : -Osteoporosis -Hyperglycemia -Risk of Infection -Poor wound healing -A vascular necrosis of bone -Hypertension

15. 5. BIOLOGICS Infliximab : -It is a Chimeric antibody (25% mouse derived, 75% human protein) Mechanism of action : It forms a relatively stable complex ↓ Binds to soluble and membrane bound TNF ↓ That blocks activation of T-lymphocytes

16. 5. BIOLOGICS Uses : -Rheumatoid arthritis - Crohn’s Disease Adverse Effects : -Infusion reactions like fever,urticaria,hypotension , dysponea -Opportunistic infection like TB , urinart tract infection

17. IMMUNOSTIMULANTS -These are drugs that enhance the immune response by inducing activation or increasing activity of any of its componants . -It is also called as immunostimulators .

18. IMMUNOSTIMULANTS Specific : Provide antigenic specificity in immune response. such as vaccines and any antigen Non-Specific : Many endogenous substances are non-specific. such as female sex hormones , other hormones like prolactin , growth hormone , vitamin D

19. IMMUNOSTIMULANTS - Levamisole : Use as an adjuvant in colon cancer -Thalidomide: Use in Rheumatoid arthritis , Lepra reaction, Multiple myeloma -BCG vaccine: Use in carcinoma - Interferone : Use in hairy cell leukaemia , malignant melanoma , AIDS related kaposi’s sarcoma

20. IMMUNOSTIMULANTS Thalidomide : -Enhanced T cell production of cytokines IL-2 ,IFN-y -Increase TNF- α in patients who are HIV seropositive -Birth defect . -Contraindicated in women having child bearing potential .