Pharmacology Nursing 3704 Corticosteroids Immunizing Hematopoietic and Immunosuppressant

Pharmacology Nursing 3704 Corticosteroids, Immunizing, Hematopoietic, and Immunosuppressant Agents By Linda Self

Immunity n n 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 nonself Normal immunity can do this by recognizing epitopes (distinctive molecules on non-self antigens)

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

Types of Immunity n n 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.

Types of Immunity n n n 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

Immunizations n n n 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

Specific recommendations n n 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

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

Agents for Active Immunity n n n 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

Agents for Active Immunity n For maximum effectiveness, must be given before actual exposure

Indications for Use 1. Routine immunization of all children against diphtheria, Haemophilus influenza, hepatitis B, mumps, pertussis, pneumococcal infection, poliomyelitis, rubella (German measles), rubeola (red measles) and varicella

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.

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

Agents for Passive Immunity n n 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

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

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

Reporting of Adverse Reactions n n 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.

Storage of Vaccines n n Most products require refrigeration at 2 to 8 degrees celsius (35. 6 to 46. 4 degrees Fahrenheit) Protect from light

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

Vaccines and Toxoids for Active Immunity n n *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; 2 nd dose at 4 -6 years.

Immunizations cont. n n n *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 2 nd 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 <2 years

Immunizations n n *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

Immunizations using toxoids n *DTa. P—at 2, 4, 6 months, at 15 -18 mos. then a booster of Td at age 4 -6 years.

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

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

Key points in Immunizations n n 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

Key Points in Immunizations n n 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.

Key Points in Immunizations n n n 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

Key Points in Immunizations n n 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

Hematopoietic and Immunostimulant Drugs n n 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

Definitions n n 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.

Cytokines n n n 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

Hematopoietic and Immunostimulant Drugs 1. 2. 3. 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.

General Characteristics cont. n n 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

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

Hematopoietic Agents n n n 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 2 x/weekly

Colony Stimulating Factors n n 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

Interleukins n n 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.

Interleukins cont. n n n 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

Interleukins cont. n n 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.

Interferons n n n Interferon alfa-2 a and 2 b are used to treat hairy cell leukemia and Kaposi’s sarcoma Interferon alfa-2 b useful also for tx of chronic hepatitis and condyloma acuminata Interferon alfa-n 1 approved for tx of chronic hepatitis C Interferon beta for multiple sclerosis Other uses under investigation Main SE are flu-like S/S

Bacillus Calmette-Guerin n n 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

Corticosteroids and Immunosuppressants n 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

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

Corticosteroid effects on the body n n n 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

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

Corticosteroids n n n Prednisone is the prototype Celestone (betamethasone) Decadron (dexamethasone) Solucortef (methylprednisolone) Kenalog (triamcinolone)

Indications for Steroids n n 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

Immunosuppressant Drugs n n 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.

Immunosuppressants n n 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

Immunosuppressants—Cytotoxic, Antiproliferative Agents n n n Damage or kill cells that are able to reproduce Used primarily in cancer Imuran (azathioprine) is an antimetabolite that interferes with the production of DNA and RNA so blocks cellular reproduction, growth and development

Cytotoxic Agents cont. n n n Imuran targets rapidly proliferating cells including T and B lymphocytes Well abosorbed orally Used mainly to prevent organ graft rejection but has little effect on acute rejection Lifelong administration Dosage depends on WBC count

Cytotoxic Agents n n Rheumatrex (methotrexate) is a folate antagonist. Inhibits biosynthesis of DNA and cell reproduction of immune cells, especially T cells. Used both for cancer and for autoimmune or inflammatory disorders (psoriasis and arthritis). Also used to prevent graft-versus-host disease.

Conventional Antirejection Agents n n Sandimmune (cyclosporine) and Prograf (tacrolimus) are fungal metabolites with strong immunosuppressive effects. Action is to inhibit synthesis of a cytokine, IL-2, necessary for activation of T cells and B cells. Rapamune (sirolimus) affects T cell activation and proliferation secondary to several interleukins.

Antirejection Agents cont. n n Sandimmune is used to prevent rejection reactions and prolong graft survival after solid organ transplantation, or to treat chronic rejection Water insoluble so prepared in etoh or olive oil for oral admin. And in castor oil or etoh for IV admin.

Antirejection Drugs cont. n n Prograf (tacrolimus) prevents rejection of transplanted organs by inhibiting growth and proliferation of T lymphocytes Multiple drug interaction as metabolized by cytochrome p 450 Is a macrolide Showing promise in preventing liver and intestinal transplantations

Antibody Preparations n n n Prepared in lab or in animals injected with human lymphoid tissue to stimulate an immune response May be monoclonal or polyclonal mixtures of antibodies (eg Ig. A, Ig. D, Ig. E, Ig. G, or Ig. M) Designed to suppress the specific components of the immune system that are causing the damage

Antibody Preparations Monoclonal antibodies n Remicade (infliximab) humanized Ig. G monoclonal antibody used to treat RA and Crohn’s. Inhibits cytokine, TNF-alfa, from binding to its receptors. n Can cause hypersensitivity reactions n Can cause infections and hypersensitivity reactions

Miscellaneous Immunosuppressants n n n Enbrel (etanercept) is a manufactured TNF receptor binder that prevents it from binding with normal receptors. TNF is a cytokine that enhances leukocyte migration into areas of tissue injury and induces the production of other cytokines. Used to treat RA

Misc. Immunosuppressants cont. n n n Arava (leflunomide) has both antiproliferative and antiinflammatory activities Inhibits the synthesis of pyrimidines, essential for RNA and DNA synthesis. Used to treat RA.

Immunosuppressants cont. n n Imuran—be aware of bone marrow depression With Sandimmune—closely monitor for s/s of renal or hepatic compromise, hypertension, anaphylaxis or CNS toxicity (seizures, tremors) Methotrexate—bone marrow depression, hepatotoxicity and GI disorders Remicade—infusion reactions, GI upset and resp. s/s