Download disease-modifying antirheumatic drugs

Biologic Response–Modifying and
Antirheumatic Drugs
Winter 2013
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Immunomodulators (IMs)

Include drugs from several classes
◦ Immunosuppressants
◦ Immunizing drugs

Biologic response modifiers (BRMs)
 Hematopoietic drugs
 Immunomodulating drugs
Winter 2013
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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
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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
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BRMs: Subclasses
Hematopoietic drugs
 Interferons (IFNs)
 Monoclonal antibodies
 Interleukin receptor agonists and
antagonists
 Disease-modifying antirheumatic
drugs
 Miscellaneous drugs

Winter 2013
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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
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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
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Hematopoietic Drugs (cont’d)

HDs are used to:
◦ Decrease the duration of chemotherapyinduced anemia, neutropenia, and
thrombocytopenia
◦ Enable higher doses of chemotherapy to be
given
◦ Other uses
Winter 2013
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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
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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
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Hematopoietic Drugs (cont’d)

darbepoetin Alpha (Aranesp)
◦ Longer-acting form of epoetin Alpha
◦ Also used to stimulate RBC
production
Winter 2013
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Hematopoietic Drugs (cont’d)

filgrastim (Neupogen)
◦ Granulocyte colony-stimulating factor (GCSF)
◦ Stimulates precursor cells for the type of
WBCs known as granulocytes

pegfilgrastim (Neulasta)
◦ Longer-acting form of filgrastim
Winter 2013
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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 colonystimulating factor (GM-CSF)
Winter 2013
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Hematopoietic Drugs (cont’d)

oprelvekin (Neumega)
◦ Also classified as an interleukin (IL-11)
◦ Stimulates bone marrow cells
(megakaryocytes) that eventually become
platelets
Winter 2013
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Hematopoietic Drugs:
Indications

Used in patients who have
experienced destruction of bone
marrow cells as a result of cytotoxic
chemotherapy
Winter 2013
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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 fungalinfected cells
Winter 2013
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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
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Hematopoietic Drugs:
Adverse Effects

Usually mild
◦
◦
◦
◦
◦
Fever
Muscle aches
Bone pain
Flushing
Others
Winter 2013
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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
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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
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Interferons (IFNs)

Proteins with three basic
properties
◦ Antiviral
◦ Antitumor
◦ Immunomodulating

Used to treat certain viral
infections and cancer
Winter 2013
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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
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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
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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
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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
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Interferons (cont’d)

Three major classes of IFNs
◦ Alpha
◦ Beta
◦ Gamma
Winter 2013
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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
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Interferons (cont’d)

Interferon beta products
◦ IFN beta-1a
◦ IFN beta-1b

Interferon gamma products
◦ Interferon gamma-1b
Winter 2013
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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
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Winter 2013
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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
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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
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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
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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
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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
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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
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Interleukins (cont’d)

anakinra (Kineret)
◦ IL-1 receptor antagonist
◦ Used to control symptoms of rheumatoid
arthritis
Winter 2013
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Rheumatoid Arthritis

Autoimmune disorder causing inflammation
and tissue damage in joints

Diagnosis primarily symptomatic

Treatment consists of NSAIDs and diseasemodifying antirheumatic drugs
Winter 2013
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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
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Antirheumatoid Arthritis Drugs (cont’d)

Methotrexate

etanercept (Enbrel)

abatacept (Orencia)

leflunomide (Arava)
Winter 2013
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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
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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
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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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