chapter 47 biologic response–modifying and antirheumatic drugs copyright © 2014 by mosby, an...
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Chapter 47
Biologic Response–Modifying and Antirheumatic Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Alter the body’s response to diseases such as cancer and autoimmune, inflammatory, and infectious diseases Hematopoietic drugs Immunomodulating drugs
• Interferons
• Monoclonal antibodies
• interleukin receptor agonists and antagonists
• Miscellaneous drugs
Biologic Response–Modifying Drugs
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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
Immunomodulating Drugs
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Fourth part of cancer therapy, in addition to: Surgery Chemotherapy Radiation
Also used for other diseases Autoimmune Inflammatory Infectious
Biologic Response Modifiers (BRMs)
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Hematopoietic drugs Interferons (IFNs) Monoclonal antibodies Interleukin receptor agonists and antagonists Disease-modifying antirheumatic drugs Miscellaneous drugs
BRMs: Subclasses
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Enhancement or restoration of the host’s immune system defenses against the tumor
Direct toxic effect on the tumor cells, which causes them to lyse, or rupture
Adverse modification of the tumor’s biology, which makes it harder for the tumor cells to survive and reproduce
BRMs: Mechanisms of Action
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Two components of the immune system work together to recognize and destroy foreign particles and cells in the blood or other body tissues
Humoral immunity Mediated by B-cell functions (antibodies)
Cell-mediated immunity (CMI) Mediated by T-cell functions
The Immune System
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Tumor antigens (chemical or tumor “markers”) label tumor cells as abnormal cells
Antibodies attack tumor cells B-lymphocytes (B cells) from the humoral immune
system T-lymphocytes (T cells) from the cell-mediated
immune system
The Immune System (cont’d)
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B-lymphocytes (B cells) Originate from bone marrow When a foreign substance (antigen) is present, these
turn into plasma cells, which in turn produce antibodies
Antibody-antigen complex Memory cells
Humoral Immune System
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Antibodies also known as immunoglobulins (Ig) Monoclonal antibodies Five major types of naturally occurring
immunoglobulins IgA, IgD, IgE, IgG, IgM
Humoral Immune System (cont’d)
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T-lymphocytes (T cells) Originate from bone marrow but mature in the thymus
gland Three types with different functions
Cytotoxic T cells T-helper cells T-suppressor cells
Cell-Mediated Immune System
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Cytotoxic T cells directly kill their targets by causing cell lysis or rupture
T-helper cells direct the actions of many other components of the immune system
T-suppressor cells serve to limit or control the immune response
Cell-Mediated Immune System (cont’d)
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A healthy immune system has about twice as many T-helper cells as T-suppressor cells at any one time
Overactive T-suppressor cells may be responsible for clinically significant cancer cases by permitting tumor growth beyond immune system control
Cell-Mediated Immune System (cont’d)
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Other cells of the cell-mediated immune system help to destroy cancer cells Macrophages (derived from monocytes) Natural killer (NK) cells Polymorphonuclear (PMN) leukocytes (neutrophils)
Cell-Mediated Immune System (cont’d)
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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
Therapeutic Effects of BRMs
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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
Hematopoietic Drugs (HDs)
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HDs are used to: Decrease the duration of chemotherapy-induced
anemia, neutropenia, and thrombocytopenia Enable higher doses of chemotherapy to be given Other uses
Hematopoietic Drugs (cont’d)
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Erythropoietic drugs epoetin alfa (Epogen, Procrit) darbepoetin alfa (Aranesp)
Colony-stimulating factors (CSFs) filgrastim (Neupogen) pegfilgrastim (Neulasta) sargramostin (Leukine)
Platelet-promoting drugs oprelvekin (Neumega)
Hematopoietic Drugs (cont’d)
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Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia
Allow for higher dosages of chemotherapy Decrease bone marrow recovery time after bone
marrow transplantation or irradiation Stimulate other cells in the immune system to
destroy or inhibit the growth of cancer cells, as well as virus- or fungus-infected cells
Hematopoietic Drugs: Mechanism of Action
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filgrastim (Neupogen) Granulocyte colony-stimulating factor (G-CSF) Stimulates precursor cells for the type of WBCs
known as granulocytes Administered before patient develops infection
pegfilgrastim (Neulasta) Longer-acting form of filgrastim
Hematopoietic Drugs (cont’d)
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sargramostim (Leukine) Granulocyte-macrophage colony-stimulating factor
(GM-CSF) Stimulates bone marrow precursor cells that make
both granulocytes and phagocytic (cell-eating) cells; known as monocytes
Indicated for promoting bone marrow recovery after autologous (own marrow) or allogenic (donor marrow) bone marrow transplantation in patients with leukemia and lymphoma
Hematopoietic Drugs (cont’d)
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oprelvekin (Neumega) Both a hematopoietic drug and one of the interleukins
(IL-11) Enhances synthesis of platelets Indicated for the prevention of chemotherapy-induced
severe thrombocytopenia and avoidance of the need for platelet transfusions
Hematopoietic Drugs (cont’d)
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Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy
Hematopoietic Drugs:Indications
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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
Hematopoietic Drugs:Indications (cont’d)
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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
Hematopoietic Drugs:Indications (cont’d)
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Classroom Response Question
A patient’s chemotherapy has ended at 1800 on a Tuesday afternoon. When is it appropriate to start therapy with filgrastim?
A.1800 on Tuesday
B.0600 on Wednesday
C.1800 on Wednesday
D.1 week later, 1800 the next Tuesday
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Usually mild Most common include:
Fever Muscle aches Bone pain Flushing
Hematopoietic Drugs:Adverse Effects
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Proteins with three basic properties Antiviral Antitumor Immunomodulating
Used to treat certain viral infections and cancer Alpha, beta, and gamma interferons
Interferons (IFNs)
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Manufactured from Escherichia coli bacteria with rDNA technology
Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens
Interferons (cont’d)
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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
Interferons (cont’d)
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Interferons:Effects on Immune System
Restore the immune system’s function if it is impaired
Augment the immune system’s ability to function as the body’s defense
Inhibit the immune system from working Helpful in autoimmune disorders
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Viral infections Genital warts, hepatitis
Cancer Chronic myelogenous leukemia, follicular lymphoma,
hairy-cell leukemia, Kaposi’s sarcoma, malignant melanoma
Autoimmune disorders Multiple sclerosis
Interferons: Indications
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Flulike effects Fever, chills, headache, myalgia
Dose-limiting adverse effect is fatigue Other adverse effects
Anorexia Dizziness Nausea Vomiting Diarrhea
Interferons: Adverse Effects
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Interferon alfa products: “leukocyte interferons”—produced from human leukocytes interferon alfa-2a interferon alfa-2b interferon alfa-n3 interferon alfacon-1 peginterferon alfa-2a peginterferon alfa-2b
Interferons (cont’d)
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Interferon beta products interferon beta-1a interferon beta-1b
Interferon gamma products interferon gamma-1b (Actimmune)
Interferons (cont’d)
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Treatment of cancer, rheumatoid arthritis, multiple sclerosis, and organ transplantation
Specifically target cancer cells and have minimal effect on healthy cells
Fewer adverse effects than traditional antineoplastic medications
Monoclonal Antibodies (MABs)
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Cancer treatment alemtuzumab (Campath) bevacizumab (Avastin) cetuximab (Erbitux) gemtuzumab ozogamicin (Mylotarg)
Other disease processes, including rheumatoid arthritis adalimumab (Humira) infliximab (Remicade) natalizumab (Tysabri)
Monoclonal Antibodies (MABs) (cont’d)
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Classroom Response Question
Which statement regarding use of monoclonal antibodies in the treatment of cancer does the nurse identify as being true? Monoclonal antibodies
A.are not as effective as other chemotherapy drugs.
B.have few adverse effects.
C.may cause flulike effects but do not cause the typical adverse effects associated with chemotherapy.
D.are only used in cases of last resort when other chemotherapy drugs have failed.
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Beneficial antitumor action Interleukin receptor agonists
aldesleukin (IL-2) oprelvekin (IL-11)* denileukin diftitox tocilizumab (IL-6) anakinra
*Also classified as an HD
Interleukins
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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
Interleukins: Capillary Leak Syndrome
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aldesleukin (Proleukin) Treatment of metastatic renal cell carcinoma and
metastatic melanoma Off-label uses include HIV infection and AIDS, and
non-Hodgkin’s lymphoma
Interleukins (cont’d)
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anakinra (Kineret) IL-1 receptor antagonist Used to control symptoms of rheumatoid arthritis
Interleukins (cont’d)
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Autoimmune disorder causing inflammation and tissue damage in joints
Diagnosis primarily symptomatic Treatment consists of NSAIDs and disease-
modifying antirheumatic drugs
Rheumatoid Arthritis
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Another type of arthritis Age-related degeneration of joint tissues Pain and reduced function
Osteoarthritis
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Modify the disease of rheumatoid arthritis Exhibit antiinflammatory, antiarthritic, and
immunomodulating effects Inhibit the movement of various cells into an
inflamed, damaged area, such as a joint Slow onset of action of several weeks, versus
minutes to hours for NSAIDs Also referred to as slow-acting antirheumatic
drugs (SAARDs)
Disease-Modifying Antirheumatic Drugs (DMARDs)
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methotrexate leflunomide (Arava) hydroxychloroquine sulfasalazine
Nonbiologic DMARDs
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adalimumab anakinra etanercept infliximab adalimumab abatacept rituximab tocilizumab Others
Biologic DMARDs
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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
Disease-Modifying Antirheumatic Drugs (DMARDs) (cont’d)
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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
Disease-Modifying Antirheumatic Drugs (DMARDs) (cont’d)
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Assess for allergies, specifically allergies to egg proteins, IgG, or neomycin
Assess for conditions that may be contraindications
Assess baseline blood counts; perform cardiac, renal, and liver studies
Assess for presence of infection
Nursing Implications
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Follow specific guidelines for preparation and administration of drugs
Monitor the patient’s response during therapy
Nursing Implications (cont’d)
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Teach patients to report signs of infection immediately Sore throat Diarrhea Vomiting Fever over 100.5° F (38.1° C) or higher
Nursing Implications (cont’d)
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Monitor for therapeutic responses Decrease in growth of lesion or mass Improved blood counts Absence of infection, anemia, and hemorrhage
Monitor for adverse effects
Nursing Implications (cont’d)
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Case Study
A 40-year-old female patient is seen in the clinic. She has been newly diagnosed with rheumatoid arthritis. Which medication does the nurse anticipate being ordered for the patient?
A.methotrexate
B.adalimumab
C.infliximab
D.etanercept
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Case Study (cont’d)
Prior to administering methotrexate, it is most important for the nurse to assess the patient for
A.allergy to eggs.
B.congestive heart failure.
C.latent tuberculosis.
D.hypothyroidism.
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Case Study (cont’d)
The patient is scheduled for discharge. Which information does the nurse include when teaching the patient about methotrexate therapy?
A.You can expect to develop mouth sores that will improve with time when taking this medication.
B.Administer the methotrexate injection daily in the early morning.
C.Mix the methotrexate with sterile saline prior to administration.
D.Administer the methotrexate subcutaneously into the thigh, abdomen, or upper arm, rotating injection sites.
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Case Study (cont’d)
The patient improved within the first three months of treatment with methotrexate. Six months later, the patient experienced worsening of symptoms. The prescriber will most likely order which monoclonial antibody for the treatment of rheumatoid arthritis?
A.adalimumab (Humira)
B.trastuzumab (Herceptin)
C.rituximab (Rituxan)
D.cetuximab (Erbitux)
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