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Biologic Response–Modifying and Antirheumatic Drugs

Biologic Response–Modifying and Antirheumatic Drugs. Immunomodulators (IMs). Include drugs from several classes Immunosuppressants Immunizing drugs Biologic response modifiers (BRMs) Hematopoietic drugs Immunomodulating drugs. Immunomodulating Drugs.

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Biologic Response–Modifying and Antirheumatic Drugs

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  1. Biologic Response–Modifying and Antirheumatic Drugs Winter 2013

  2. Immunomodulators (IMs) Include drugs from several classes Immunosuppressants Immunizing drugs Biologic response modifiers (BRMs) Hematopoietic drugs Immunomodulating drugs Winter 2013

  3. Immunomodulating Drugs Medications that therapeutically alter a patient’s immune response to malignant tumor cells Drugs that modify the body’s own immune response so that it can destroy various viruses and cancerous cells Winter 2013

  4. Biologic Response Modifiers (BRMs) Fourth part of cancer therapy, in addition to: Surgery Chemotherapy Radiation Also used for other diseases Autoimmune Inflammatory Infectious Winter 2013

  5. BRMs: Subclasses Hematopoietic drugs Interferons (IFNs) Monoclonal antibodies Interleukin receptor agonists and antagonists Disease-modifying antirheumatic drugs Miscellaneous drugs Winter 2013

  6. Therapeutic Effects of BRMs Regulation or enhancement of the immune response Cytotoxic or cytostatic activity against cancer cells Inhibition of metastases, prevention of cell division, or inhibition of cell maturation Winter 2013

  7. Hematopoietic Drugs HDs promote the synthesis of various types of major blood components by promoting the growth, or differentiation, and function of their precursor cells in the bone marrow Produced by rDNA technology Winter 2013

  8. Hematopoietic Drugs (cont’d) HDs are used to: Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia Enable higher doses of chemotherapy to be given Other uses Winter 2013

  9. Hematopoietic Drugs (cont’d) Erythropoietic drugs epoetin Alpha (Epogen, Procrit) darbepoetin Alpha (Aranesp) Colony-stimulating factors (CSFs) filgrastim (Neupogen) pegfilgrastim (Neulasta) sargramostin (Leukine) Platelet-promoting drugs oprelvekin (Neumega) Winter 2013

  10. Hematopoietic Drugs (cont’d) epoetin Alpha (Epogen, Procrit) Synthetic derivative of the hormone erythropoietin Promotes the synthesis of RBCs by stimulating RBC precursors Winter 2013

  11. Hematopoietic Drugs (cont’d) darbepoetin Alpha (Aranesp) Longer-acting form of epoetin Alpha Also used to stimulate RBC production Winter 2013

  12. Hematopoietic Drugs (cont’d) filgrastim (Neupogen) Granulocyte colony-stimulating factor (G-CSF) Stimulates precursor cells for the type of WBCs known as granulocytes pegfilgrastim (Neulasta) Longer-acting form of filgrastim Winter 2013

  13. Hematopoietic Drugs (cont’d) sargramostim (Leukine) Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes Granulocyte-macrophage colony-stimulating factor (GM-CSF) Winter 2013

  14. Hematopoietic Drugs (cont’d) oprelvekin (Neumega) Also classified as an interleukin (IL-11) Stimulates bone marrow cells (megakaryocytes) that eventually become platelets Winter 2013

  15. Hematopoietic Drugs:Indications Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy Winter 2013

  16. Hematopoietic Drugs:Indications (cont’d) Decrease the duration of low neutrophil counts, thus reducing the incidence and duration of infections Enhance the functioning of mature cells of the immune system, resulting in greater ability to kill cancer cells as well as viral- and fungal-infected cells Winter 2013

  17. Hematopoietic Drugs:Indications (cont’d) Also enhance RBC and platelet counts in patients with bone marrow suppression resulting from chemotherapy Allow for higher doses of chemotherapy, resulting in the destruction of a greater number of cancer cells Winter 2013

  18. Hematopoietic Drugs:Adverse Effects Usually mild Fever Muscle aches Bone pain Flushing Others Winter 2013

  19. Hematopoietic Drugs: Epoetin FDA warning Increased adverse effects when used by patients with higher-than-normal hemoglobin Heart attack Heart failure Stroke Death Winter 2013

  20. Hematopoietic Drugs:Interactions Filgrastim and sargramostim should not be given within 24 hours of myelosuppressive antineoplastic therapy These two types of drugs will directly antagonize each other Winter 2013

  21. Interferons (IFNs) Proteins with three basic properties Antiviral Antitumor Immunomodulating Used to treat certain viral infections and cancer Winter 2013

  22. Interferons (cont’d) Manufactured from Escherichia coli bacteria with rDNA technology Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens Winter 2013

  23. Interferons (cont’d) Recombinantly made IFNs are identical to the IFNs that are present within the human body and have the same properties IFNs protect human cells from viruses and prevent cancer cells from dividing and replicating Winter 2013

  24. Interferons: Indications Viral infections Genital warts, hepatitis Cancer Chronic myelogenous leukemia, follicular lymphoma, hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma Autoimmune disorders Multiple sclerosis, others Winter 2013

  25. Interferons: Adverse Effects Flulike effects Fever, chills, headache, myalgia Dose-limiting adverse effect is fatigue Other adverse effects Anorexia Dizziness Nausea Vomiting Diarrhea Winter 2013

  26. Interferons (cont’d) Three major classes of IFNs Alpha Beta Gamma Winter 2013

  27. Interferons (cont’d) Interferon alpha products: “leukocyte interferons”—produced from human leukocytes Interferon Alpha-2a, Interferon Alpha-2b Interferon Alpha-n3, Interferon Alphacon-1 Peginterferon Alpha-2a Peginterferon Alpha-2b Winter 2013

  28. Interferons (cont’d) Interferon beta products IFN beta-1a IFN beta-1b Interferon gamma products Interferon gamma-1b Winter 2013

  29. Monoclonal Antibodies (MABs) Used to target specific cancer cells Minimal effect on healthy cells Fewer adverse effects than traditional antineoplastic medications Used to treat cancers and rheumatoid arthritis Winter 2013

  30. Winter 2013

  31. Monoclonal Antibodies (MABs) (cont’d) Cancer treatment alemtuzumab (Campath) bevacizumab (Avistatin) cetuximab (Erbitux) gemtuzumab ozogamicin (Mylotarg) Other disease processes, including rheumatoid arthritis adalimumab (Humira) infliximab (Remicade) natalizumab (Tysabri) Winter 2013

  32. Monoclonal Antibodies (MABs) (cont’d) Mechanisms of action and adverse effects vary with each drug Used for specific types of cancer and in organ transplantation Extremely specific drugs that target certain tumor cells and bypass normal cells Winter 2013

  33. Interleukins and Related Drugs Beneficial antitumor action Interleukin receptor agonists aldesleukin (IL-2, Proleukin) oprelvekin (IL-11, Neumega)* denileukin diftitox (Ontak) IL-1 receptor antagonist anakinra (Kineret) *Also classified as an HD Winter 2013

  34. Interleukins (cont’d) Aldesleukin acts indirectly to stimulate or restore immune response Aids in causing T cells to multiply, including lymphokine-activated killer (LAK) cells LAK cells recognize and destroy only cancer cells, and ignore normal cells Used for metastatic renal cell carcinoma and malignant melanoma Under study for use in other types of cancer Winter 2013

  35. Interleukins: Capillary Leak Syndrome Severe toxicity of aldesleukin therapy Capillaries lose ability to retain vital colloids in the blood; these substances are “leaked” into the surrounding tissues Result: massive fluid retention Respiratory distress Heart failure MI Dysrhythmias Reversible after interleukin therapy is discontinued Winter 2013

  36. Interleukins (cont’d) denileukin diftitox IL-2 receptor antagonist (IL-2Ra) Binds to cell-surface IL-2 receptors on normal as well as certain malignant cells Causes cell death Winter 2013

  37. Interleukins (cont’d) anakinra (Kineret) IL-1 receptor antagonist Used to control symptoms of rheumatoid arthritis Winter 2013

  38. Rheumatoid Arthritis Autoimmune disorder causing inflammation and tissue damage in joints Diagnosis primarily symptomatic Treatment consists of NSAIDs and disease-modifying antirheumatic drugs Winter 2013

  39. Antirheumatoid Arthritis Drugs Also known as disease-modifying antirheumatic drugs (DMARDs) Slow onset of action—several weeks May take 3 to 6 months to see full effects Can have much more toxic adverse effects than NSAIDs Antiinflammatory, antiarthritic, immunomodulating effects Winter 2013

  40. Antirheumatoid Arthritis Drugs (cont’d) Methotrexate etanercept (Enbrel) abatacept (Orencia) leflunomide (Arava) Winter 2013

  41. Antirheumatoid Arthritis Drugs (cont’d) etanercept (Enbrel) Used to treat rheumatoid arthritis (including juvenile RA) and psoriasis Patients must be screened for latex allergy (some dosage forms may contain latex) Onset of action: 1 to 2 weeks Contraindicated in presence of active infections Reactivation of hepatitis and TB have been reported Winter 2013

  42. Antirheumatoid Arthritis Drugs (cont’d) abatacept (Orencia) Used to treat rheumatoid arthritis Caution if history of recurrent infections or COPD Patients must be up-to-date on immunizations before starting therapy May increase risk of infections associated with live vaccines May decrease response to vaccines Winter 2013

  43. Nursing Implications (cont’d) Teach patients to report signs of infection immediately Sore throat Diarrhea Vomiting Fever over 100° F Winter 2013

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