Drugs for new era

1. IMMUNOMODULATORS
MODERATORS
Dr R Ramesh, MD, Professor
Dr K Thulasiram, MD, Associate Professor
Dr V Rushendrakumari, MD, Assistant Professor
Dr Aparna, MD, Assistant Professor
Presented by,
Dr Arun R M

2. INTRODUCTION
• Etymology of immunity
• Definition of immunity
• Types of immunity

3. COMPONENTS OF IMMUNE SYSTEM
• Granulocytes
• Complement synthesis & Antibody formation
• Cellular immunity
• Mucocutaneous barriers

4. MECHANISM OF IMMUNOMODULATON
• Ag recognition & phagocytosis
• Lymphocyte proliferation/differentiation
• Antibody synthesis
• Ag-Ab interaction
• Release of mediators
• Modification of target tissue response

5. IMMUNOSUPPRESSANTS
• Glucocorticoids
• Calcineurin inhibitors
• Antiproliferative agents
• Antibodies

6. GLUCOCORTICOIDS
• MECHANISM OF ACTION
Lymphocyte homing
Down regulation of IL 2,3,6
Inhibition of T cell proliferation
Increased destruction of lymphoid cells

7. • USES
Transplant rejection
BM transplantation
AI diseases
Psoriasis
IBD

8. • TOXICITY
Infection
Poor wound healing
DM
HTN
Cataract
AVN of bone
Growth retardation

9. CALCINEURIN INHIBITORS

10. CYCLOSPORIN
• Cyclic peptide composed of 11 AA
• Inhibit T cell proliferation & IL2
• Lymphocytes arrested at G0/G1 phase
• Binds to cytosolic protein cyclophilin of T lymphocytes
• Complex of cyclosporin & cyclophilin inhibit calcineurin

11. • USES
Organ transplantation
AI diseases

12. • TOXICITY
Nephrotoxicity
Hyperuricemia
Hyperplasia of gum
Hirsutism
Tremor

13. TACROLIMUS (FK506)
• Macrolide that is isolated from soil fungus
• Binds to FK506 binding protein
• Inhibit calcineurin
• Block transcription of IL2

14. • TOXICITY
Nephrotoxicity
Neurotoxicity
DM
Infections

15. ANTIPROLIFERATIVE/ANTIMETABOLIC DRUG
• Sirolimus
• Azathioprine
• Mycophenolate mofetil
• Methotrexate
• Cyclophosphamide

16. SIROLIMUS
• Macrolide antibiotic
• Binds to FK506 binding protein
• Inhibit mTOR
• metabolized by CYP3A4
• Eliminated by biliary route

17. USES
Prophylaxis of organ transplant
Toxicity
Anemia
Thrombocytopenia
Hypokalemia
dyslipidemia

18. AZATHIOPRINE
• Purine antimetabolite
• Affects differentiation & function of T cells
• Inhibit T lymphocytes
• Prevention of organ transplant rejection
• Used in RA also

19. TOXICITY
 Bone marrow suppression
Hepatotoxicity
Alopecia

20. MYCOPHENOLATE MOFETIL
• Prodrug of Mycophenolic acid
• Inhibit Inosine monophosphate dehydrogenase enzyme in guanine
synthesis
• Inhibit lymphocyte proliferation

21. USES
Prophylaxis of renal transplant rejection
Non nephrotoxic combination in patients developing nephropathy
TOXICITY
Leucopenia
Diarrhea

22. CYCLOPHOSHAMIDE
• Effect on B cells & Humoral immunity
• Short course high dose in BM transplantation
• Reserve drug in other organ transplantation

23. USES
RA
SLE
ITP
Pemphigus
TOXICITY
Haemorrhagic cystitis
Alopecia
Cardiac toxicity

24. METHOTREXATE
• Folate antagonist
• Decrease cytokine production & cellular immunity
• Used in
RA
Psoriasis
Pemphigus

25. TOXICITY
BM suppression
Hepatotoxicity
Acute renal failure
Ulcerations in GIT & skin

26. FINGOLIMOD
• Sphingosine 1 phosphate receptor agonist
• Lymphocyte homing
• Protect graft from T cell mediated attack
• Immunosuppression therapy in prevention of a/c graft reaction

27. TOXICITY
Lymphopenia
Macular edema
Bradycardia

28. ANTIBODIES
• Ant thymocyte globulin
• Monoclonal Antibodies
• Anti TNF agents

29. ANTITHYMOCYTE GLOBULIN
• Polyclonal antibody purified from horse or rabbits, immunized with
human thymic lymphocytes
• Binds to T lymphocytes & depletes them
• Induction of immunosuppression in transplantation
• Toxicity
Hypersensitivity reaction

30. ANTI CD3 ANTIBODY
• Muromonab
• Binds to CD3 on Helper T cells
• Used in a/c organ transplant rejection
• Toxicity
cytokine release syndrome
Aseptic meningitis
Pulmonary edema

31. ANTI IL2 ANTIBODY
• Daclizumab
• Block IL2 mediated T cell activation
• Prophylaxis of a/c organ rejection
• Toxicity
Anaphylaxis
Opportunistic infections

32. ANTI TNF AGENTS
• INFLIXIMAB
• Used in
RA
IBD
Psoriasis
• Toxicity
Infusion reactions

34. IMMUNOSTIMULANTS
• Levamisole
• Thalidomide
• BCG
• Interferons
• IL2

35. LEVAMISOLE
• Orally active levo isomer of Tetramisole
• Restores depressed T cell function
• Acts by raising c-GMP level
• Used in
malignancy
recurrent aphthous
recurrent Herpes

36. THALIDOMIDE
• Increase T cell production of Cytokines- IL2, IFN gamma
• NK cell mediated cytotoxicity against tumor cells
• Used in multiple myeloma & ENL

37. BCG VACCINE
• Immunological enhancer to stimulate intact immune system
• Muramyl dipeptide is the immunostimulant component
• Principle target cell is T lymphocytes
• Stimulate macrophage function & phagocytic activity

38. INTERFERONS
• Low molecular weight glycoprotein cytokines produced by host cells
in response to viral infection
• Binds to cell surface receptor
• Inhibit viral replication

39. INTERFERON ALPHA 2b
Uses
Hairy cell leukemia
Malignant melanoma
Kaposi Sarcoma
Toxicity
Flu like symptoms
CNS depression
Arrhythmia

40. IL-2 ( ALDESLEUKIN)
• Promotes T cell differentiation
• Used in
Metastatic RCC
Malignant melanoma
• Toxicity
flu like symptoms
hupotension

41. IMMUNOGLOBULINS
INDICATIONS
Immunodeficiency
When time is inadequate for active immunization
Rabies
Hepatitis B

42. Rh IMMUNOGLOBULIN
• Antibody against Rh Ag on RBC surface
• Binds with Rh Ag & does not allow them to induce Ab formation
• Used for preventing HDN
• Given at 28th week of pregnancy

43. THANK YOU