biologic response–modifying and antirheumatic drugs 1winter 2013
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Biologic Response–Modifying and Antirheumatic Drugs
1Winter 2013
Immunomodulators (IMs)
Include drugs from several classes◦ Immunosuppressants◦ Immunizing drugs
Biologic response modifiers (BRMs) Hematopoietic drugs Immunomodulating drugs
2Winter 2013
Immunomodulating DrugsImmunomodulating 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
3Winter 2013
Biologic Response Modifiers Biologic Response Modifiers (BRMs)(BRMs)
Fourth part of cancer therapy, in addition to:◦Surgery◦Chemotherapy◦Radiation
Also used for other diseases◦Autoimmune◦ Inflammatory◦ Infectious
4Winter 2013
BRMs: SubclassesBRMs: Subclasses
Hematopoietic drugsInterferons (IFNs)Monoclonal antibodiesInterleukin receptor agonists and
antagonistsDisease-modifying antirheumatic
drugsMiscellaneous drugs
5Winter 2013
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
6Winter 2013
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
7Winter 2013
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
8Winter 2013
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)
9Winter 2013
Hematopoietic Drugs (cont’d)
epoetin Alpha (Epogen, Procrit)◦Synthetic derivative of the hormone
erythropoietin◦Promotes the synthesis of RBCs by
stimulating RBC precursors
10Winter 2013
Hematopoietic Drugs (cont’d))
darbepoetin Alpha (Aranesp)◦Longer-acting form of epoetin Alpha◦Also used to stimulate RBC
production
11Winter 2013
Hematopoietic Drugs (cont’d)
filgrastim (Neupogen)◦Granulocyte colony-stimulating factor (G-
CSF)◦Stimulates precursor cells for the type of
WBCs known as granulocytespegfilgrastim (Neulasta)◦Longer-acting form of filgrastim
12Winter 2013
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)
13Winter 2013
Hematopoietic Drugs (cont’d)
oprelvekin (Neumega)◦Also classified as an interleukin (IL-11)◦Stimulates bone marrow cells
(megakaryocytes) that eventually become platelets
14Winter 2013
Hematopoietic Drugs:Indications
Used in patients who have experienced destruction of bone marrow cells as a result of cytotoxic chemotherapy
15Winter 2013
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
16Winter 2013
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
17Winter 2013
Hematopoietic Drugs:Adverse Effects
Usually mild◦Fever◦Muscle aches◦Bone pain◦Flushing◦Others
18Winter 2013
Hematopoietic Drugs: Epoetin
FDA warning◦Increased adverse effects when used
by patients with higher-than-normal hemoglobin Heart attack Heart failure Stroke Death
19Winter 2013
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
20Winter 2013
Interferons (IFNs)
Proteins with three basic properties◦Antiviral◦Antitumor◦Immunomodulating
Used to treat certain viral infections and cancer
21Winter 2013
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
22Winter 2013
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
23Winter 2013
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
24Winter 2013
Interferons: Adverse Effects
Flulike effects◦ Fever, chills, headache, myalgia
Dose-limiting adverse effect is fatigue
Other adverse effects◦ Anorexia◦ Dizziness◦ Nausea◦ Vomiting◦ Diarrhea
25Winter 2013
Interferons (cont’d)
Three major classes of IFNs◦Alpha◦Beta◦Gamma
26Winter 2013
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
27Winter 2013
Interferons (cont’d)
Interferon beta products◦IFN beta-1a◦IFN beta-1b
Interferon gamma products◦Interferon gamma-1b
28Winter 2013
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
29Winter 2013
30Winter 2013
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)
31Winter 2013
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
32Winter 2013
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
33Winter 2013
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
34Winter 2013
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
35Winter 2013
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
36Winter 2013
Interleukins (cont’d)
anakinra (Kineret)
◦ IL-1 receptor antagonist ◦Used to control symptoms of rheumatoid
arthritis
37Winter 2013
Rheumatoid Arthritis
Autoimmune disorder causing inflammation and tissue damage in joints
Diagnosis primarily symptomatic
Treatment consists of NSAIDs and disease-modifying antirheumatic drugs
38Winter 2013
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
39Winter 2013
Antirheumatoid Arthritis Drugs (cont’d)
Methotrexate
etanercept (Enbrel)
abatacept (Orencia)
leflunomide (Arava)
40Winter 2013
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
41Winter 2013
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 vaccines42Winter 2013
Nursing Implications (cont’d)
Teach patients to report signs of infection immediately◦Sore throat◦Diarrhea◦Vomiting◦ Fever over 100° F
43Winter 2013