Pharmacology Nursing 3704 Corticosteroids, Immunizing,Hematopoietic, and Immunosuppressant Agents

1. PharmacologyNursing 3704Corticosteroids, Immunizing,Hematopoietic, andImmunosuppressant Agents By Linda Self

2. Immunity • Last line of defense against infection • Has characteristics of specificity, memory and inducibility to provide long-term protection against specific antigens • Must have ability to distinguish self from non-self • Normal immunity can do this by recognizing epitopes (distinctive molecules on non-self antigens)

3. Immunity cont. • Hyperactive system will create autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, others • When system is underactive, immunodeficiency diseases occur

4. Types of Immunity • Natural immunity-general protective mechanisms that protect an individual from infectious agents that cause disease in other species • Acquired immunity—active or passive. Active immunity is caused by own immune systems, passive immunity is where antibodies are “transferred” to the host. Active immunity tends to be longer lasting than passive.

5. Types of Immunity • Cellular—involving activated T lymphocytes in body tissues • Humoral immunity involves B lymphocytes and antibodies. • Interplay between two types of immunity; virtually all antigens elicit both cellular and humoral responses

6. Immunizations • Involves administration of an antigen to induce antibody formation (for active immunity) or serum from immune people (for passive immunity) • Immunizations are biologic agents • Are regulated by the U.S. FDA

7. Specific recommendations • Only use the inactivated form of polio vaccine in US; unfortunately is injectible only • Hepatitis B recommended now recommended for all newborns and for non-immunized children before starting school

8. Specific Recommendations cont. • Everyone should be immunized against diphtheria and tetanus every 7 to 10 years for life • Combining vaccinations to prompt greater compliance include: IPV with DTaP with hepatitis B (Pediarix), Haemophilus b (Hib) with hepatitis B (Comvax), and hepatitis A&B=Twinrix.

9. Agents for Active Immunity • Vaccines and toxoids • Vaccines are suspensions of microorganisms or their antigenic products that have been killed or attenuated; may have lifelong effects • Toxoids are bacterial toxins or products that have been modified to destroy toxicity while retaining antigenic properties; not permanent effects

10. Agents for Active Immunity • For maximum effectiveness, must be given before actual exposure

11. Indications for Use • Routine immunization of all children against diphtheria, Haemophilus influenza, hepatitis B, mumps, pertussis, pneumococcal infection, poliomyelitis, rubella (German measles), rubeola (red measles) and varicella

12. Indications for Use cont. 2. Immunizations of adolescents and adults against diphtheria and tetanus 3. Immunization of prepubertal girls or women of childbearing age against rubella. 4. Immunization of adults and children at high risk for exposure to a particular disease such as yellow fever, malaria, etc.

13. Contraindications to Use of agents for active immunity • Febrile illnesses • If receiving immunosuppressive therapy • In immunodeficiency states • Leukemia • Lymphoma • In pregnancy • If generalized malignancy is present

14. Agents for Passive Immunity • Immune serums are the biologic products used for passive immunity • Only create temporary immunity • Goal is to prevent or modify the disease process • Are made from the serum of individuals with high concentrations of the specific antibody or immunoglobulin required

15. Agents for Passive Immunity • Cytomegalovirus • Hepatitis B • Rabies • Rubella • Tetanus • Varicella zoster • Respiratory syncytial virus infections

16. Reporting of Vaccine preventable diseases • Report to the local or state health department • Information is then sent to the CDC • www.cdc.gov/nip/acip is authoritative site

17. Reporting of Adverse Reactions • All health care providers must report any serious adverse reactions to the Department of Health and Human Services • Website is: www.fda.gov/cber/vaers.html.

18. Storage of Vaccines • Most products require refrigeration at 2 to 8 degrees celsius (35.6 to 46.4 degrees Fahrenheit) • Protect from light

19. Vaccines and Toxoids for Active Acquired Immunity • *Haemophilus Influenza (Hib)—age 2-5 mos. Then q2mos x 3 doses; then at 12-15 mos.

20. Vaccines and Toxoids for Active Immunity • *Hepatitis B—children at birth, repeat in one month then again six months later; different preparations such as Recombivax and Engerix • *Measles, Mumps and Rubella—12-15 months; 2nd dose at 4-6 years.

21. Immunizations cont. • *Poliomyelitis—sub Q injection. Give at 2, 4, 6-18 mos then at 4-6 years • Influenza—may start at greater than 6 months. Give one dose then follow by 2nd dose in one month. If 9 years or older, require only one dose. • Meningococcal—effective against Neisseria meningitidis. Type A should only be given to infants and children <2years

22. Immunizations • *Pneumococcal 7 valent conjugate (Prevnar) give at 2, 4, and 6 mos. then again at 12-15 months. • *Varicella—12 months or older, follow by a second dose 4-8 weeks after the first dose; booster at age 12 years

23. Immunizations using toxoids • *DTaP—at 2, 4, 6 months, at 15-18 mos. then a booster of Td at age 4-6 years.

24. Immune Serums for Passive Immunity • Cytomegalovirus • Hepatitis B • Immune globulin in case of hepatitis A, measles, varicella, rubella, bacterial infections • Rabies immune globulin • RSV immune globulin • RhoGAM

25. New vaccines • HPV—bivalent and quadravalent vaccines • Herpes Zoster • HIV • Immunizing the unborn eg RSV • Malaria vaccinate the infected to prevent passage to others

26. Key points in Immunizations • Determine whether patient has any conditions that contraindicate administration of immunizing agents • For children with chronic illnesses such as asthma, heart disease, diabetes and others, flu vaccine is recommended annually after 6 months of age

27. Key Points in Immunizations • For children with HIV, live viral and bacterial vaccines are contraindicated as they can cause disease (MMR, varicella, bacillus Calmetter-Guerin). • Annual influenza vaccine and one time pneumococcal vaccine at 65 years recommended for healthy older adults and those with chronic conditions.

28. Key Points in Immunizations • To avoid rubella induced abnormalities in fetal development, women of childbearing age must avoid becoming pregnant for 3 months following being immunized • Likewise for Varicella • After receiving Varicella vaccine, aboid close contact with newborns, pregnant women and anyone who is immunocompromised

29. Key Points in Immunizations • After receiving a vaccine, stay in the area for approx. 30 minutes • Give DTP in lateral thigh muscle of infant • Aspirate carefully before IM or Sub-q injection of any immunizing agent • With varicella vaccine, salicylates my increase risk of Reye’s

30. Hematopoietic and Immunostimulant Drugs • Cytokines or biologic response modifiers are given to restore normal function or to increase the ability of the immune system to eliminate potentially harmful invaders • Examples are colony-stimulating factors, several interferons and two interleukins

31. Definitions • Interferons are glycoproteins with antiviral activity • Interleukins are cytokines that enable communication among leukocytes and other cells active in inflammation or the cell-mediated immune response. Result—a maximized response to a microorganism or other foreign antigen.

32. Cytokines • Are substances produced by bone marrow cells, activated helper T cells, activated macrophages and other cells. • Regulate cellular activities by acting as chemical messengers among cells. • Helper T cells and macrophages are the main producers of cytokines • Act by binding to receptors on the membranes of numerous types of target cells. • Are the key components in producing hematopoietic and immunostimulant drugs

33. Hematopoietic and Immunostimulant Drugs • Most hematopoietic and immunostimulant drugs are facsimiles of cytokines • The endogenous cytokines control the reproduction, growth and differentiation of stem cells and colony forming units; these agents are simulated. • The manufactured cytokines involve inserting the identified genes that are involved in their production into yeasts or bacteria; thus producing the substances exogenously.

34. General Characteristics cont. • Very powerful biologic response modifiers • May be difficult to maintain an effective dose levels for prolonged treatment periods • Can have untoward and unanticipated side effects • Can act as antiproliferative and immunoregulatory agents; can augment the activity of natural killer cells and/or enhance activities of immune cells

35. General Characteristics cont. • Cannot be take orally • May have substantial side effects decreasing patient compliance

36. Hematopoietic Agents • Epogen or Procrit (Darbepoetin alfa and epoetin alfa)==drug preparations of erythropoietin • Use to treat anemias • Dosage is adjusted according to response; should be adjusted with when hematocrit approaches 36%; check HCT 2x/weekly

37. Colony Stimulating Factors • Neupogen (filgrastim),Neulasta (pegfilgrastim) are used to stimulate blood cell production by the bone marrow in patients with bone marrow transplantation or chemotherapy-induced neutropenia • Leukine (sargramostim) GM-CSF used as above but also useful as angiogenetic in ischemic heart disease

38. Interleukins • Proleukin (aldesleukin) is a recombinant DNA version of interleukin 2. Function is to activate cellular immunity; produces tumor necrosis factor and inhibits tumor growth • Used to treat metastatic renal cell CA and melanoma; others under investigation.

39. Interleukins cont. • Proleukin is contraindicated in recent organ transplantation or with serious cardiopulmonary disease • Proleukin may cause renal and/or hepatic impairment • Toxicity of this agent can cause: GI bleed, CNS coma, cardiac dysrhythmias or respiratory embarrassment

40. Interleukins cont. • If toxicity occurs, dosage reduction is not the recommendation. Either DC the drug or withhold one or two doses. • Neumega (oprelvekin) is recombinant IL-11. Used to prevent severe thrombocytopinia and to reduce the need for platelet tranfusions in patients receiving cancer chemotherapy.

41. Interferons • Interferon alfa-2a and 2b are used to treat hairy cell leukemia and Kaposi’s sarcoma • Interferon alfa-2b useful also for tx of chronic hepatitis and condyloma acuminata • Interferon alfa-n1 approved for tx of chronic hepatitis C • Interferon beta for multiple sclerosis • Other uses under investigation • Main SE are flu-like S/S

42. Bacillus Calmette-Guerin • Suspension of attenuated Mycobacterium bovis • Stimulates cell-mediated immunity • Used as a topical agent for superficial cancers of the urinary bladder with an 80% response rate • Contraindicated in immunosuppression as can cause TB in high risk populations

43. Corticosteroids and Immunosuppressants • These drugs are used to decrease an inappropriate or undesirable immune response for certain conditions. Examples include RA, SLE, asthma or suppression of transplant rejection

44. Corticosteroids Glucocorticoids • Reduce immune response and reduce inflammation • Used as anti-inflammatory, immunosuppressive, antiallergic and antistress • SE include infection, decreased wound healing, HPA axis suppression, osteoporosis, hyperglycemia, and muscle wasting

45. Corticosteroid effects on the body • Increase production and decrease utilization of glucose in the blood • Catabolic—protein depletion • Decrease inflammatory response by stabilizing lysosomal membranes • Decrease immune response by decreasing antibody production, lymphocytes, eosinophils, macrophages and lymphoid tissue. • More neutrophils leave marrow but fewer are involved in inflammatory processes

46. Corticosteroids cont. • Stabilize mast cells thus the release of histamine • Affect stomach mucous contributing to the development of peptic ulcers • Muscle atrophy • Adrenal cortex suppression

47. Corticosteroids • Prednisone is the prototype • Celestone (betamethasone) • Decadron (dexamethasone) • Solucortef (methylprednisolone) • Kenalog (triamcinolone)

48. Indications for Steroids • Asthma, COPD, arthritis • Adrenal insufficiency • Cancer—inhibit cell reproduction and are cytotoxic to lymphocytes; excellent for tx of cerebral edema, GVHD after bone marrow transplantation • Chemotherapy-induced emesis

49. Immunosuppressant Drugs • Used in conjunction with steroids • Used in autoimmune disorders • Used to reduce the immune response when foreign tissue is transplanted into the body • Older drugs depressed immune system; had unfortunate SE. Infections, cancer, hypertension and metabolic bone disease.

50. Immunosuppressants • Have developed new agents that modify the immune response • Newer agents target specific components of the immune response so will have less global effect on patient’s total immunity, susceptibility to infection