IMMUNE SYSTEM DRUGS

1. IMMUNE SYSTEM DRUGS Ph.Waleed M. Al Shehri Satellite Pharmacist Walshehri@kfmc.med.sa Department of pharmacy King Fahad Medical City

2. OUTLINE Definition and examples of Immunomodulating drugs. Classification and examples of immunosuppressive drugs

3. IMMUNOMODULATING AGENTS Agents that act as stimulators of immune responses. Have important therapeutic uses, including the treatment of immune deficiency diseases, chronic infectious diseases, and cancer.

4. IMMUNOMODULATING AGENTS Aldesleukin: Aldesleukin is in a class of drugs known as cytokines, Aldesleukin increases the body ability to fight cancer. Interferons: Interferons are a group of proteins produced by white blood cells, fibroblasts, or T-cells as part of an immune response to a viral infection or other immune trigger.

5. IMMUNOMODULATING AGENTS BCG (Bacille Calmette-Gu�rin): BCG is an effective immunization against tuberculosis. Thymosin: Is a hormone secreted from the thymus. Its primary function is to stimulate the production of T cells, which are an important part of the immune system.

6. IMMUNOSUPPRISSIVE DRUGS

7. WHAT IS IMMUNOSUPPRISSIVE DRUGS? Any of a variety of substances used to prevent production of antibodies. They are commonly used to prevent rejection by a recipient's body of an organ transplanted from a donor. Immunosuppressive drug has one meaning: a drug that lowers the body's normal immune response.

8. CLASSIFICATION OF IMMUNOSUPRISSIVE DRUGS

9. DRUGS ACTING ON IMMUNOPHILINS

10. CYCLOSPORINE Clinical uses: Cyclosporine was discovered in the 1970s, but was not approved for use until 1983. Cyclosporine used in solid organ transplantation and in graft-versus-host syndrome in bone marrow transplants.

11. CYCLOSPORINE Doses: Adults, children, P.O: Initial: 14-18 mg/kg/day, beginning 4-12 hr prior to organ transplantation. Maintenance: 5-10 mg/kg/day divided every 12-24 hrs; maintenance dose is usually tapered to 3-10 mg/kg/day.

12. CYCLOSPORINE Adverse effect: Nephrotoxicity is the most common and important adverse effect of cyclosporine. Infections in patient taking Cyclosporine are common and may be life-threatening. Viral infections due to herpes group. Lymphoma may occur, presumable due to immunosuppression. Other toxicities include hypertension, hyperkalemia, tremor, hirsutism, glucose intolerance, and gum hyperplasia.

13. CYCLOSPORINE Monitoring Parameters: Cyclosporine trough levels. Serum electrolytes. Renal function. Hepatic function. Blood pressure. serum cholesterol.

15. TACROLIMUS Clinical uses: It was first approved by the Food and Drug Administration (FDA) in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow, and limb transplants.

16. TACROLIMUS Doses: Cardiac transplant rejection; Prophylaxis: initial, 0.075 mg/kg/day ORALLY in 2 divided doses (given every 12 h). Liver transplant rejection; Prophylaxis: initial, 0.1 to 0.15 mg/kg/day ORALLY in 2 divided doses (given every 12 h). Renal transplant rejection; Prophylaxis: initial, 0.2 mg/kg/day ORALLY in 2 divided daily doses (given every 12 h).

17. TACROLIMUS Adverse effect: Nephrotoxicity. Hyperglycemia. Hyperkalemia. Hypomagnesaemia. Tremor. Headache. Diarrhea. Hypertension.

18. TACROLIMUS Monitoring parameters: Blood pressure. Echocardiography. Hepatic and renal function. Electrolyte (especially magnesium and potassium). Fasting glucose. CBC. signs and symptoms of rejection, serum tacrolimus levels.

20. CORTICOSTEROIDS

21. PREDNISOLONE  Clinical uses: Prednisolone is used alone or in combination with other agents in a wide variety of medical conditions involving an undesirable immunologic reaction. Used to suppress immunologic reactions in patients who undergo organ transplantation.

22. PREDNISOLONE DOSES: 0.1-2 mg/kg/day

23. PREDNISOLONE Adverse effect: Insomnia, Nervousness. Increased appetite, indigestion. Diabetes mellitus. Glaucoma. Epistaxis.

24. PREDNISOLONE Monitoring parameters: Clinical improvement. Blood pressure. Electrolyte. Blood glucose. Mental status. Ophthalmic exam (with prolonged therapy). Signs and symptoms of infection.

26. ANTIMETABOLITES

27. AZATHIOPRINE Clinical use: Azathioprine is used in autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis). As immunosuppression in renal homografts.

28. AZATHIOPRINE DOSES: I.V. dose is equivalent to oral dose. Dose should be based on ideal body weight. Children and adults: -Starting dose: 2-5 mg/kg/day. -Maintenance dose:1-2 mg/kg/day.

29. AZATHIOPRINE Adverse effect: Fever. Nausea. Bone marrow suppression. Thrombocytopenia. Leucopenia. Anemia. Hepatotoxicity.

30. AZATHIOPRINE Monitoring parameters: CBC, platelets counts. Total bilirubin. Alkaline Phosphatase. liver function.

32. MYCOPHENOLATE Clinical uses: The drug has been used successfully as a sole agent in Kidney, Liver, and heart transplants. In renal transplants, it�s used with low-dose cyclosporine has reduced cyclosporine-induced nephrotoxicity.

33. MYCOPHENOLATE DOSES: Cardiac transplant: 1.5 g IV/ORAL twice daily. Liver transplant: 1 g IV twice daily or 1.5 g ORALLY twice daily. Renal transplant: 1 g IV/ORAL twice daily.

34. MYCOPHENOLATE Adverse effect: 1% to 10% Thrombophlebitis and thrombosis, 4% with I.V administration.

35. MYCOPHENOLATE Monitoring parameters: Signs and symptoms of rejection. CBC. Renal function. Blood pressure. Heart rate. Electrolytes. Hepatic function. Cardiac and pulmonary function. Signs and symptoms of lymphoma. Signs and symptoms of infections.

37. ANTIBODIES AS IMMUNOSUPPRESSANT

38. ANTIBODIES AS IMMUNOSUPPRISSANT Antibodies are used as a quick and potent immunosuppression method to prevent the acute rejection reaction.

39. Lymphocyte Immune Globulin Clinical use: Used prior to bone marrow transplantation to prevent the graft-versus-host (GVH) reaction. It is also used in combination with cyclosporine or cytotoxic drugs (or both) for maintenance following bone marrow, heart, and renal transplantation.

40. Lymphocyte Immune Globulin Adverse effect: Chills or fever in most patients. May cause hypersensitivity reactions. Pain and erythema occur at injection sites. Lymphoma has been noted as late complication. Risk of developing an infection. Risk of bleeding.

41. RhO (D) Immune Globulin Clinical use: Rho (D) immune globulin is used for prevention of Rho hemolytic disease of the newborn. In women treated with Rho (D) immune globulin, maternal antibodies to Rh-positive cells are not produced in subsequent pregnancies, and hemolytic disease of the neonate is averted.

42. Monoclonal Antibodies Examples: Muromonab-CD3 Daclizumab.

43. Muromonab-CD3 Clinical use: Is used to manage a renal homograft rejection crisis.

44. Muromonab-CD3 DOSES: Cardiac transplant rejection, Steroid-resistant: 5 mg IV bolus once daily for 10 to 14 days; begin after corticosteroid therapy has failed. Renal transplant rejection: 5 mg IV bolus once daily for 10 to 14 days. Renal transplant rejection; Prophylaxis: 5 mg IV once daily for 5 to 14 days.

45. Muromonab-CD3 Adverse effect: Diarrhea, Nausea, Vomiting. Anaphylaxis, Neoplastic disease. Encephalopathy. Blindness AND/OR vision impairment level, Irreversible. Pulmonary edema. Infectious disease. Inflammatory disorder.

46. Muromonab-CD3 Monitoring parameters: Signs and symptoms of rejection. Blood pressure. Fluid status. Neurologic symptoms. CBC. Renal and hepatic function. Muromonab-CD3 plasma levels.

47. DACLIZUMAB Clinical use: These saturate the receptors and prevent T cell activation and thus prevent formation of antibodies against the transplant. Daclizumab is not used for acute rejection episodes.

48. DACLIZUMAB DOSES: Renal transplant rejection, With regimen including cyclosporine and corticosteroids: 1 mg/kg IV beginning within 24 h prior to transplant, then 1 mg/kg IV every 14 days for a total of 5 doses.

49. DACLIZUMAB Adverse effect: Edema. Hypertension. Hypotension. Tachyarrhythmia. Bleeding. Blood coagulation disorder. Dyspnea. Fever. Infectious disease.

50. DACLIZUMAB Monitoring parameters: Signs/symptoms of rejection. CBC . Renal function. Acute hypersensitivity reactions (including anaphylaxis). Signs and symptoms of infection.

51. REFERENCES Lippincott�s illustrated reviews: pharmacology, Third edition, by Richard D. Howland And Mary Mycek, 2006. Clinical pharmacology Resource Group, Robarts Research Institute, London, Ontario, Canada. Medline plus, U.S. National Library of Medicine. Pharmacology Lange, Antony J. Trevor, Bertram Katzung 6th edition. Drug information LEXI, American pharmaceutical association 2005/2006. Clinican�s Handbook, Seymour Ehrenpreis PhD Pharmacology, Chicago medical school. Pharmacotherapy Handbook 2000. MICROMEDEX� Healthcare Series, Thomson Healthcare 2007.