Drugs for Immune System

1. Drugs for Immune System M ARIS WIDODO PPD UNISMA

2. Immune System “a biochemical complex that protects the body against pathogenic organisms and other foreign bodies. The system incorporates the humoral immune response, which produces antibodies to react with specific antigens, and the cell mediated response, which uses T-cells to mobilize tissue macrophages in the presence of a foreign body.” Mosby’s Pocket Dictionary, p. 530

3. Lines of Protection/Defense • Compare and contrast the body’s protection against pathogens. • First line (non-specific) • Second line (specific)

4. Immune System • Defends the body against invading pathogens, foreign antigens, and its own cells that become cancerous • Can also sometimes attack itself, causing “autoimmune diseases” or immune-mediated diseases • Participates in analphylaxis & tissue/organ rejection

5. Immune Response • Compare and contrast the divisions of the immune response. • Humoral • Cell mediated

6. Vaccines • Prototype: Hepatitis B Vaccine, p. 460 • .

7. Cytokines • Hormone-like substance that: • Regulate the intensity and duration of response • Mediate cell-to-cell communication .

8. Immunosuppressants • Agents that decrease or prevent an immune response, thus suppressing the immune system • Used to prevent or treat rejection of transplanted organs

9. Immunosuppressants (cont’d) • All suppress certain T-lymphocyte cells lines, preventing their involvement in the immune response • Result: a pharmacologically immunocompromised state • Mechanisms of action vary according to agent

10. Corticosteroids azathioprine muromonab-CD3 daclizumab sirolimus cyclophosphamide cyclosporine tacrolimus basiliximab glatiramer acetate Immunosuppressants (cont’d)

11. Immunosuppressants (cont’d) • Indications vary from agent to agent • Primarily indicated for the prevention of organ rejection • Some also used for immunological diseases such as rheumatoid arthritis and multiple sclerosis

12. Immunosuppressants (cont’d) • azathioprine • Used as an adjunct medication to prevent rejection of kidney transplants • Also used in the treatment of rheumatoid arthritis

13. Immunosuppressants (cont’d) • cyclosporine • Primary agent used in the prevention of kidney, liver, heart, and bone marrow transplant rejection • May be used for other autoimmune disorders • tacrolimus • Used for the prevention of liver and kidney transplant rejection

14. Immunosuppressants (cont’d) • glatiramer acetate • The only immunosuppressant agent used for the treatment of multiple sclerosis (MS) • Used to reduce the frequency of MS relapses (exacerbations) in relapsing-remitting multiple sclerosis (RRMS)

15. Immunosuppressants (cont’d) • Side effects vary according to agents, and may be devastating **All immunosuppressed clients have a heightened susceptibility to opportunistic infections**

16. Immunizing Biologicals • Biological antimicrobial agents • Also called biologicals • Antitoxins • Serum • Toxoids • Vaccines • Used to prevent, treat, or cure infectious diseases

17. Toxoids • Antigenic (foreign) preparations or bacterial exotoxins • Detoxified with chemicals or heat • Cannot revert back to a toxic form • Stimulate one’s immune system to produce a specific antibody • The production of these antibodies protect against future exposures to the antigen • Ex. Tetanus

18. Vaccines • Suspensions of live, attenuated (weakened) or killed (inactivated) micro-organisms • The weakened form prevents the person from contracting the disease

19. Vaccines (cont’d) • Also stimulate the production of antigens against a specific antibody • Vaccinations with live bacteria or virus provide lifelong immunity • Vaccinations with killed bacteria or virus provide partial immunity, and booster shots are needed periodically

20. Active Immunization • The body is exposed to a relatively harmless form of an antigen • The immune system is stimulated, and “remembers” this antigen if subsequent exposures occur • The immunizations do not cause a full-blown infection

21. Examples of Active Immunizing Agents • BCG vaccine (tuberculosis) • Diphtheria,tetanus, and pertussis toxoids, several forms • Cholera vaccine • Haemophilus influenzae type b conjugate vaccine • Hepatitis A and B virus vaccines • Measles, mumps, and rubella virus vaccine, live—several forms • Poliovirus vaccine, several forms

22. Examples of Active Immunizing Agents (cont’d) • Rabies virus vaccine • Smallpox virus vaccine • Tetanus toxoid • Varicella virus vaccine (chicken pox) • Yellow fever virus vaccine

23. Indications • Active immunization • Prevents infection caused by bacterial toxins or viruses • Provides long-lasting or permanent immunity • “Herd immunity”

24. Passive Immunization • Serum or concentrated immune globulins from humans or animals are injected into a person • The substances needed to fight off invading micro-organisms are given directly to a person • The immune system is bypassed • Short-lived compared with active immunization, but works faster

25. Passive Immunization (cont’d) • Naturally acquired passive immunity • From mother to fetus through the placenta • From mother to infant through breast milk • Artificially acquired passive immunity • Acquired from an external source, such as injection of antibodies or immunoglobulins

26. Examples of Passive Immunizing Agents • Antivenins • Diphtheria antitoxin • Hepatitis B immune globulin • Immune globulin, various forms • Rabies immune globulin (human) • Rh0(D) immune globulin (RhoGAM) • Tetanus immune globulin • Varicella zoster immune globulin (chicken pox/shingles)

27. Indications (cont’d) • Passive immunization • Antitoxins, antivenins, immune globulins • Minimizes effects of poisoning by the venoms of spiders and certain snakes • Provides quick immunity before a person’s own immune system has a chance to make antibodies (such as in cases of exposure to hepatitis B or rabies viruses)

28. Indications (cont’d) • National Advisory Committee on Immunization recommendations for adult and pediatric immunizations (Canada) • Provide specific dosages and intervals for immunizations

29. Mechanism of action:vaccines Anitgens: foreign substances Anitbodies: immunoglobulins Once the vaccine is administered the body produces immunoglobulins: IgG, IgA, IgE, IgD, IgM to attack and kill the foreign invader Anitbody titre: the amount of immunoglobulin in the body that must be present to protect the body against the pathogen Booster shot: given when antibody titre reveals low levels

30. Side Effects • Range from mild and transient to very serious or life threatening • Minor effects • Fever, minor rash, soreness at injection site, itching • Severe effects • Fever >38° C, encephalitis, convulsions, anaphylactic reaction, dyspnea, others

31. 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.

32. 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.

33. IMMUNOMODULATING AGENTS • BCG (Bacille Calmette-Guérin): 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.

34. IMMUNOSUPPRISSIVE DRUGS

35. 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.

36. CLASSIFICATION OF IMMUNOSUPRISSIVE DRUGS DRUGS ACTING ON IMMUNOPHILINS: Cyclosporine, Tacrolimus. ADRINOCORTICOIDS: Methylprednisolone, Prednisolone, Prednisone. ANTIBODIES: Lymphocyte Immune Globulin, Rh0 (D) Immune Globulin, Monoclonal antibodies. IMMUNOSUPPRISSIVE ANTIMETABOLITES: Azathioprine, mycophenolate mofetil.

37. 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.

38. 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.

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

40. 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.

41. 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).

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

43. CORTICOSTEROIDS

44. 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.

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

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

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

48. 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.

49. 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.

50. 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.