Pharm ch 47- Biologic Response-Modifying and Antirheumatic Drugs

Interferon beta products

-interferon beta-1a, -interferon beta-1b

Disease-Modifying Antirheumatic Drugs (DMARDs)

-Modify the disease of rheumatoid arthritis. -Slow onset of action of several weeks, versus minutes to hours for NSAIDs. -Also referred to as slow-acting antirheumatic drugs (SAARDs).

T-suppressor cells

-Opposite of T helper cells. -Regulate immune response. -Allow tumors to grow. -serve to limit or control the immune response.

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.

Therapeutic Effects of Biologic Response Modifiers (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.

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. -Reversible after interleukin therapy is discontinued.

abatacept (Orencia) (a DMARD):

-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.

Hematopoietic Drugs:Adverse Effects

-Usually mild. -Most common include: ---Fever, ---Muscle aches, ---Bone pain, ---Flushing,

Monoclonal Antibodies (MABs) other disease treatment drugs

-adalimumab (Humira), -infliximab (Remicade), -natalizumab (Tysabri),

Interleukin receptor agonists

-aldesleukin (IL-2), -oprelvekin (IL-11), -denileukin diftitox, -tocilizumab (IL-6), -anakinra.

Monoclonal Antibodies (MABs) Cancer treatment drugs

-alemtuzumab (Campath), -bevacizumab (Avastin), -cetuximab (Erbitux), -gemtuzumab ozogamicin (Mylotarg).

Erythropoietic drugs (HDs drugs) examples:

-epoetin alfa (Epogen, Procrit). -darbepoetin alfa (Aranesp).

Colony-stimulating factors (CSFs) (HDs drugs) examples:

-filgrastim (Neupogen). -pegfilgrastim (Neulasta). -sargramostin (Leukine).

Nonbiologic DMARDs examples

-methotrexate, -leflunomide (Arava), -hydroxychloroquine, -sulfasalazine,

What should the patient report immediately?

-signs of infection: ---Sore throat, ---Diarrhea, ---Vomiting, ---Fever over 100.5° F (38.1° C) or higher.

Hematopoietic Drugs classes

-Erythropoietic drugs. -Colony-stimulating factors (CSFs). -Platelet-promoting drugs.

Monoclonal Antibodies (MABs): Adverse Effects

-Fewer adverse effects than traditional antineoplastic medications. -Flu-like symptoms.

Capillary Leak Syndrome may result in?

-Respiratory distress, -Heart failure, -MI, -Dysrhythmias,

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.

aldesleukin (Proleukin) (an Interleukin):

-Treatment of metastatic renal cell carcinoma and metastatic melanoma. -Off-label uses include HIV infection and AIDS, and non-Hodgkin's lymphoma.

Interferons (IFNs)

-Used to treat certain viral infections and cancer. -Alpha, beta, and gamma interferons.

filgrastim (Neupogen) (HDs drug): Mechanism of Action:

Stimulates precursor cells for the type of WBCs known as granulocytes.

Interferons: Cancer Indications

-Chronic myelogenous leukemia, -follicular lymphoma, -hairy-cell leukemia, -Kaposi's sarcoma, -malignant melanoma

Monitor for therapeutic responses:

-Decrease in growth of lesion or mass. -Improved blood counts. -Absence of infection, anemia, and hemorrhage.

Nursing Implications

-Assess for conditions that may be contraindications. -Assess baseline blood counts; perform cardiac, renal, and liver studies. -Assess for presence of infection. -Monitor the patient's response during therapy.

Rheumatoid Arthritis

-Autoimmune disorder causing inflammation and tissue damage in joints. -Diagnosis primarily symptomatic.

Biologic Response Modifiers (BRMs) Also used for other diseases, such as?

-Autoimmune. -Inflammatory. -Infectious.

Humoral Immune System includes?

-B-lymphocytes (B cells). -Antibody-antigen complex. -Memory cells. -Antibodies also known as immunoglobulins (Ig). -Monoclonal antibodies.

etanercept (Enbrel) (a DMARD): Onset of Action

1 to 2 weeks

Biologic DMARDs examples

adalimumab, anakinra, etanercept, infliximab, adalimumab, abatacept, rituximab, tocilizumab, Others.

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)

A. Adalimumab (Humira) is indicated for the treatment of severe, progressive RA for which other RA therapies have failed. Trastuzumab (Herceptin) is indicated for the treatment of breast cancer. Rituximab (Rituxan) is used for the treatment of non-Hodgkin's lymphoma, and cetuximab (Erbitux) is indicated for the treatment of metastatic colorectal cancer.

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

A. For the treatment of rheumatoid arthritis, the recommend therapy with nonbiologic DMARDs usually begins with methotrexate or leflunomide for most patients. Biologic DMARDs are generally reserved for those patients whose disease does not respond to methotrexate or leflunomide. The biologic DMARDs include etanercept, infliximab, adalimumab, abatacept, and rituximab.

While teaching a patient about the possible adverse effects of the interferons, the nurse should mention which effects? (Select all that apply) A. Myalgia. B. Fever. C. Diarrhea. D. Fatigue. E. Chills. F. Dizziness.

A. Myalgia. B. Fever. C. Diarrhea. D. Fatigue. E. Chills.

An immunoglobulin that binds to antigens to form a special complex

Antibody

A substance that is recognized as foreign by the body's immune system.

Antigen

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

C. Filgrastim and sargramostim have significant drug interactions when given with myelosuppressive antineoplastic drugs. Typically filgrastim and sargramostim are not given within 24 hours of administration of myelosuppressive antineoplastics.

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.

C. Prior to administering DMARDs, it is important for the nurse to assess the patient for contraindications to the use of DMARDs such as active bacterial infections, active herpes, active/latent tuberculosis, and acute or chronic hepatitis B or C.

The nurse is monitoring a patient who has been receiving aldesleukin (IL-2) (Proleukin) for treatment of malignant melanoma. Which adverse effect, if noted on assessment, is of primary concern? A. Chills. B. Fatigue. C. Headache. D. Fluid retention.

D. Fluid retention.

oprelvekin (Neumega) (HDs drug): Mechanism of Action

Enhances synthesis of platelets

oprelvekin (Neumega) (HDs drug): Indications

For the prevention of chemotherapy-induced severe thrombocytopenia and avoidance of the need for platelet transfusions.

Biologic Response Modifiers (BRMs)

Fourth part of cancer therapy, in addition to: -Surgery. -Chemotherapy. -Radiation.

sargramostim (Leukine) (HDs drug)

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

Disease-Modifying Antirheumatic Drugs (DMARDs): Mechanism of Action

Inhibit the movement of various cells into an inflamed, damaged area, such as a joint.

T-lymphocytes (T cells).

Originate from bone marrow but mature in the thymus gland

sargramostim (Leukine) (HDs drug): Indications

Promoting bone marrow recovery after autologous (own marrow) or allogenic (donor marrow) bone marrow transplantation in patients with leukemia and lymphoma

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.

Immunomodulating Drugs: Mechanism of Action

-Therapeutically alter a patient's immune response to malignant tumor cells. -Modify the body's own immune response so that it can destroy various viruses and cancerous cells.

Biologic Response-Modifying Drugs classes

-Hematopoietic drugs. -Immunomodulating drugs.

pegfilgrastim (Neulasta) (HDs drug):

Longer-acting form of filgrastim

Cytokines that are produced by sensitized T lymphocytes upon contact with antigen particles.

Lymphokines

Interferon alfa products: "leukocyte interferons"

-Produced from human leukocytes. -Including: ---interferon alfa-2a, interferon alfa-2b, interferon alfa-n3, interferon alfacon-1, peginterferon alfa-2a, peginterferon alfa-2b.

Interferons: Viral infections Indications

-Genital warts, -hepatitis

Hematopoietic Drugs (HDs): MoreIndications

-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.

Osteoarthritis

-Another type of arthritis. -Age-related degeneration of joint tissues. -Pain and reduced function.

Interferons (IFNs); Proteins with three basic properties:

-Antiviral. -Antitumor. -Immunomodulating.

Antibodies attack which tumor cells?

-B-lymphocytes (B cells) from the humoral immune system. -T-lymphocytes (T cells) from the cell-mediated immune system.

Interleukins

-Beneficial antitumor action, -Interleukin receptor agonists

T-helper cells

-Control immune system. -Direct other immune cells.

Cell-Mediated Immune System : Three types

-Cytotoxic T cells. -T-helper cells. -T-suppressor cells.

Hematopoietic Drugs (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 (HDs): Mechanism of Action

-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 (HDs):Indications

-Destruction of bone marrow cells as a result of cytotoxic chemotherapy. -Decrease the duration of low neutrophil counts = reducing incidence and duration of infections. -Enhance functioning of mature cells of the immune system, = greater ability to kill cancer cells as well as viral- and fungal-infected cells.

A patient will be starting therapy with etanercept (Enbrel) as part of treatment for severe rheumatoid arthritis. which conditions, if present, may be contraindictation for this drug? (Select all that apply) A. Latex allergy. B. Active bacterial infection. C. Diabetes mellitus. D. Latent tuberculosis. E. Acute hepatits B. F. Peanut allergy.

A. Latex allergy. B. Active bacterial infection. D. Latent tuberculosis. E. Acute hepatits B.

The nurse is reviewing the medical history of a patient who is about to receive therapy with etanercept (Enbrel). which conditions, if present, would be contraindicated or caution for therapy with this drug? (Select all that apply) A. Urinary tract infection. B. Psoriasis. C. Heart failure. D. Glaucoma. E. Latex allergy.

A. Urinary tract infection. C. Heart failure. E. Latex allergy.

When planning care for a patient who is receiving interferon therapy, the nurse must keep in mind that the major dose-limiting factor is A. fatigue. B. bone marrow suppression. C. fever. D. nausea and vomiting.

A. fatigue

Biologic Response-Modifying Drugs

Alter the body's response to diseases such as cancer and autoimmune, inflammatory, and infectious diseases.

Leukocytes of the humoral immune system.

B lymphocytes (B cells)

The nurse is conducting a class on drugs for malignant tumors for a group of new oncology staff members. Which best describes the action of interferons in the management of malignant tumors? A. Interferons increase the production of specific anticancer enzymes. B. Interferons have antiviral and antitumor properties and strengthen the immune system. C. Interferons stimulate the production and activation of T lymphocyes and cytotoxic T cells. D. Interferons help improve the cell-killing action of T cells because they are retrieved from healthy donors.

B. Interferons have antiviral and antitumor properties and strengthen the immune system.

oprelvekin (Neumega) (HDs drug):

Both a hematopoietic drug and one of the interleukins (IL-11)

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.

C. Because these drugs only target cancer cells, they do not have the adverse effects that are typically associated with chemotherapy. However, they do cause acute symptoms that are similar to classic allergy or flulike symptoms. As a result, these symptoms are managed during therapy.

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.

C. Methotrexate should be administered subcutaneously into the thigh, abdomen, or upper arm, rotating injection sites. Methotrexate should not be administered with other solutions and without use of a filter. Methotrexate is taken weekly. The development of stomatitis should be reported to the prescriber immediately.

The nurse is administering methotrexate as part of the treatment for rheumatoid arthritis and will monitor for which sign of bone marrow suppression? A. Edema. B. Tinnitus. C. Increased bleeding tendencies. D. Tingling in the extremities.

C. Increased bleeding tendencies.

In caring for a patient recieving therapy with a myelosuppressive antineoplastic drug, the nurse notes an order to begin filgrastim after the chemotherapy is completed. Which statement correcty describes when the the nurse will begin the filgrastin therapy? A. It can be started during the chemotherapy. B. It will begin immediately after the chemotherapy is completed. C. It will be initiated 24 hours after the chemotherapy is completed. D. It will not be started until at least 72 hours after the chemotherapy is completed.

C. It will be initiated 24 hours after the chemotherapy is completed.

A patient is starting therapy with adalimumab (Humira) after a course of therapy with methotrexate (Trexall) failed to improve the patient's condition. The nurse recognizes that this patient is being treated for which condition? A. Advanced-stage cancer. B. Multiple sclerosis. C. Severe rheumatoid arthritis. D. Systemic lupus erythematosus.

C. Severe rheumatoid arthritis.

Cytokines that regulate the growth, differentiation, and function of bone marrow stem cells.

Colony-stimulating factors

A type of cytokine that promotes resistance to viral infection in uninfected cells.

Interferons

Immunomodulating drugs includes?

Interferons -Monoclonal antibodies, -interleukin receptor agonists and antagonists, -Miscellaneous drugs.

Humoral immunity

Mediated by B-cell functions (antibodies)

Cell-mediated immunity (CMI)

Mediated by T-cell functions

Interferons: Autoimmune disorders Indications

Multiple sclerosis

Treatment of Rheumatoid Arthritis

NSAIDs and disease-modifying antirheumatic drugs.

Monoclonal Antibodies (MABs): Mechanism of Action

Specifically target cancer cells and have minimal effect on healthy cells.

sargramostim (Leukine) (HDs drug): Mechanism of Action:

Stimulates bone marrow precursor cells that make both granulocytes and phagocytic (cell-eating) cells; known as monocytes.

Leukocytes of the cell-mediated immune system.

T lymphocytes (T cells)

A healthy immune system has about twice as many of which cells?

T-helper cells as T-suppressor cells at any one time

Cell-Mediated Immune System

T-lymphocytes (T cells).

Monoclonal Antibodies (MABs) : Indications

Treatment of cancer, rheumatoid arthritis, multiple sclerosis, and organ transplantation.

Interferon gamma products

interferon gamma-1b (Actimmune)

Other cells of the cell-mediated immune system help to destroy?

cancer cells

Overactive T-suppressor cells may be responsible for?

clinically significant cancer cases by permitting tumor growth beyond immune system control

Cytotoxic T cells

directly kill their targets by causing cell lysis or rupture.

Which allergies should you assess for?

egg proteins, IgG, or neomycin, latex.

IgA

found in saliva, breast milk and colostrum, and secretions of GI and respiratory tracts.

etanercept (Enbrel) (a DMARD): Contraindications

in presence of active infections. --Reactivation of hepatitis and TB have been reported.

IgD

little known, involved in parasitic infections?

IgG

main antibody (long lasting memory)

IgE

mediates allergic reactions.

Platelet-promoting drugs (HDs drug) example:

oprelvekin (Neumega)

etanercept (Enbrel) (a DMARD)

-Used to treat rheumatoid arthritis (including juvenile RA) and psoriasis. -Patients must be screened for latex allergy (some dosage forms may contain latex).

anakinra (Kineret) (an Interleukin):

-IL-1 receptor antagonist. -Used to control symptoms of rheumatoid arthritis.

Humoral Immune System: 5 major types of naturally occurring immunoglobulins:

-IgA, -IgD, -IgE, -IgG, -IgM

Which cells of the cell-mediated immune system help to kill cancer cells?

-Macrophages (derived from monocytes). -Natural killer (NK) cells. -Polymorphonuclear (PMN) leukocytes (neutrophils).

Interferons: Adverse Effects

-Flulike effects: ---Fever, chills, headache, myalgia -Dose-limiting adverse effect is fatigue. -Other adverse effects inclued: ---Anorexia, Dizziness, Nausea, Vomiting, Diarrhea

filgrastim (Neupogen) (HDs drug):

-Granulocyte colony-stimulating factor (G-CSF). -Administered before patient develops infection.

Tumor antigens

-chemical or tumor "markers". -label tumor cells as abnormal cells.

Biologic Response Modifiers (BRMs): Subclasses

-Hematopoietic drugs. -Interferons (IFNs). -Monoclonal antibodies. -Interleukin receptor agonists and antagonists. -Disease-modifying antirheumatic drugs. -Miscellaneous drugs.

Interferons protect what cells from dividing and replicating?

-Human cells from viruses. -Cancer cells.

Biologic Response Modifiers (BRMs): Mechanism of Action

-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.

What are Interferons manufactured from?

-Escherichia coli bacteria with rDNA technology. -Also obtained from pooled human leukocytes that have been stimulated by synthetic and natural antigens.

The Immune System

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. -Cell-mediated immunity (CMI).

IgM

primary antibody produced after initial contact with antigen.