Monoclonal Antibodies Flashcards

1
Q

Muromonab-CD3 side effects

A

mild flu-like symptoms, anaphylactic reactions, CNS toxicities, side effects due to suppression of the immune system (increased risk of infection and cancer)

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2
Q

Ustekinumab (Stelara) therapeutic uses

A

Psoriasis

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3
Q

Certolizumab (Cimzia)

A

pegylated humanized Fab’ fragment of a TNF-α monoclonal antibody (NO Fc region)

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4
Q

Golimumab (Simponi) side effects

A

Serious and sometimes fatal infections

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5
Q

Brentuximab vedotin (Adcatris) therapeutic uses

A

classical Hodgkin lymphoma and systemic anaplastic large cell lymphoma

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6
Q

Trastuzumab emtansine (Kadcyla) side effects

A

nausea, fatigue, headache, constipation, musculoskeletal pain, increased liver enzymes, and thrombocytopenia

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7
Q

What test should be performed BEFORE administering Vedolizumab(Entyvio)

A

Pre-existing infection including tuberculosis

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8
Q

Abciximab (Centorex, Reopro) MOA

A

Antithrombotic—helps to prevent blood clots—the Fab fragment binds to glycoprotein receptor of human platelets and inhibits aggregation
Directed against GP IIb/IIIa receptors which are integrin family of adhesion molecules
Steric hindrance of the receptor itself as opposed to direct binding to RGD binding site of the receptor
Inhibits monocyte adhesion
Inhibits vitronectin receptors (present in serum) which mediate blood coagulation as well as endothelial and smooth muscle cell proliferation

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9
Q

Ipilimumab (Yervoy)

A

Human antibody

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10
Q

Muromonab-CD3 therapeutic uses

A

Prevent acute rejection

Used to deplete T cells from donor bone marrow prior to bone marrow transplantation

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11
Q

Alirocumab (Praluent) side effects

A

injection site bruising, flu like symptoms, nose and throat irritation, GI symptoms, muscle pain, and urinary tract infection

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12
Q

Brentuximab vedotin (Adcatris) side effects

A

Chemotherapy-induced peripheral neuropathy is one of the adverse effects of the drug.

Other side effects include, nausea, vomiting, diarrhea, cough, anemia, fatigue, upper respiratory tract infection, fever, rash, thrombocytopenia, and neutropenia.

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13
Q

Ustekinumab (Stelara)

A

Human IgG1alpha monoclonal antibody

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14
Q

Ofatumumab (Arzerra)

A

Human monoclonal antibody

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15
Q

Abciximab (Centorex, Reopro) side effects

A

nausea, vomiting, dizziness, and irritation at the injection site, occasional breathing trouble, rapid or abnormal heart beat, chest pain, swelling of feet or ankles

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16
Q

Nivolumab (Opdivo)

A

Human monoclonal antibody (IgG4)

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17
Q

Ibritumomab (Zevalin)

A

Murine monoclonal antibody

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18
Q

Abciximab (Centorex, Reopro) therapeutic uses

A

emergency care in patients with heart disease caused by poor blood flow in the arteries of heart (Ischaemic cardiac complications)

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19
Q

Reslizumab (Cinqair) administration

A

Once every 4 weeks (IV infusion can take up tp 50mins)

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20
Q

Natalizumab (Tysabri) MOA

A

specific for α-4 integrin

interferes with the cellular traffic through the cellular lining of blood-brain barrier and intestines, and as a consequences produces its anti-inflammatory effects

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21
Q

Daclizumab (Zinbryta) therapeutic uses

A

Kidney transplantation

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22
Q

Panitumumab (Vectibix) MOA

A

binds to epidermal growth factor receptors (EGFR aka:HER-1) resulting in the inhibition of signal transduction pathways

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23
Q

Muromonab-CD3 MOA

A

Binds to the CD3, antigen is blocked and cannot bind to the antigen-recognition complex
Antibody binds to T lymphocytes—total circulating T cells are depleted from the blood and when the T cells reappear, the CD3 and antigen recognition complex are absent

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24
Q

Ibritumomab (Zevalin) therapeutic uses and how is it administered

A

treatment of relapsed or refractory low grade, follicular, or transformed B cell non-Hodgkin’s lymphoma and in patients with rituximab refractory follicular non-Hodgkin’s lymphoma

Administered in two steps:

  1. patient initially receives a single infusion of rituximab which is administered to get rid of the majority of B cells (CD20 receptors) and to limit toxicity from radiation
  2. The immunoconjugate linked to Indium 111 is then transfused
  3. 7-9 days after the infusion a second infusion of rituximab is given followed by the administration of the immunoconjugate linked to Yttrium 90
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25
Q

Tocilizumab(Actemra) MOA

A

Inhibit IL-6 receptors

—binds to soluble as well as membrane bound interleukin-6 receptors

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26
Q

Nivolumab (Opdivo) therapeutic uses

A

unseceptible or metastatic melanoma, which no longer responds to other treatments

advanced squamous cell carcinoma of head and neck and squamous non-small cell lung cancer (not a cure—just prolongs life)

Late stage liver, renal, bladder and colorectal cancer it is used to prolong life

The inhibition of PD-1 system produces natural anti-cancer response

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27
Q

Benefits of antibodies that target CD20 receptors

A

Mature B cells go through some final changes to become plasma cells which are the cells that secrete antibodies—Stem cells and Plasma cells do NOT express CD20

When you use a drug that targets CD20 it has a lot of benefits because you are not destroying stem cells and therefore do not require bone marrow transplant and you are not destroying plasma cells so the body will continue to make some antibodies and the patient will not be completely Immunocompromised

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28
Q

Belimumab (Benlysta) therapeutic uses

A

Systemic lupus erythematosus

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29
Q

Palvizumab (Synagis) therapeutic uses

A

Directed against RSV

prevention of serious lower respiratory infection caused by respiratory syncytial virus (RSV)

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30
Q

Rituximab (Rituxan) MOA

A

IgG1 specific antibody for CD20 receptor contains human constant region and murine heavy and light chains variable regions

Fab domain of the antibody binds to CD20 marker on B cells
Fc domain recruits immune effector cells and mediators for B cell lysis—lysis can be achieved by antibody-dependent cell mediated cytotoxicity and apoptosis

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31
Q

Infliximab (Remicade)

A

Chimeric antibody

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32
Q

Centuximab (Erbitux) therapeutic uses

A

treatment of head, neck and colorectal cancers and in combination with radiation therapy it is indicated for the treatment of squamous cell carcinoma (locally or regionally advanced).
However, it is not given in combination with radiation to patients who did not exhibit a good response to platinum-based therapy (cannot give with KRAS then this will not work)

For metastatic colorectal carcinoma expressing EGFR it is administered in combination with irinotecan, provided that the patients are refractory to irinotecan-based chemotherapy

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33
Q

Ixekizumab (Taltz)

A

Humanized monoclonal antibody

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34
Q

Tocilizumab(Actemra) side effects

A

upper respiratory infection, common cold, HA, and high BP

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35
Q

Brentuximab vedotin (Adcatris) MOA

A

After binding to the cell surface of the target cell, it is internalized by endocytosis and selectively targets the tumor cells

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36
Q

Bevacizumab (Avastin) side effects

A

GI perforation, hemorrhage, hypertension*, complications with wound healing, nephritic syndrome, congestive heart failure and thromboembolic events

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37
Q

Daclizumab (Zinbryta) MOA

A

binds to alpha subunit of IL-2 receptors—prevents the binding of IL-2 to its receptors
Since alpha chain is not expressed on resting T cells, entire immune response may not be suppressed

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38
Q

Trastuzumab emtansine (Kadcyla) MOA

A

Mertansine enters tumor cells, binds to tubulin and kills them and as a result, it kills the cell

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39
Q

Trastuzumab emtansine (Kadcyla)

A

Conjugated antibody made up of Trastuzumab linked to cytotoxic agent Mertansine

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40
Q

Certolizumab (Cimzia) MOA

A

neutralizes membrane-bound and soluble human TNFα in a dose-dependent manner.

Most potent antibody against TNF alpha b/c it is only a fragment and can reach the tissue

It has a high affinity for TNF-α but does NOT induce antibody-dependent cellular cytotoxicity, complement activation, or apoptosis in T cells or macrophages.

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41
Q

Ixekizumab (Taltz) therapeutic uses

A

Moderate to severe psoriasis in adults

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42
Q

Trastuzumab (Herceptin)

A

Humanized monoclonal antibody (CDR grafted IgG1)

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43
Q

Infliximab (Remicade) MOA

A

Inhibits TNF alpha

Neutralizes the effects of TNF alpha which includes its effects on IL-1 and IL-6

Reduces infiltration of inflammatory cells into the inflamed areas of joints
Suppresses the expression of adhesion molecules.
Decreases IL-6 levels.
Inhibits acute phase response.

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44
Q

Centuximab (Erbitux) MOA

A

specific for epidermal growth factor receptors (HER1) which are expressed on epithelial tissue as well as on the tumors of the colon, rectum, head and neck

Causes inhibition of EGF-mediated signal transduction events including the phosphorylation and activation of various kinases associate with EGFR

The inhibition of binding of EGF to its receptors suppresses cell growth and decreases in the production of matrix metalloproteinase and vascular endothelial growth factor (VEGF)

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45
Q

Tocilizumab(Actemra)

A

Humanized antibody

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46
Q

umab

A

Human antibody

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47
Q

Panitumumab (Vectibix) therapeutic uses

A

colorectal cancer in patients who have not responded well to standard chemotherapy

Mutations called KRAS and NRAS and BRAF
—If there is a mutation in KRAS or NRAS then this antibody will not work (must test the mutations before giving the drug)

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48
Q

Reslizumab (Cinqair)

A

Humanized monoclonal antibody

49
Q

Ibritumomab (Zevalin) side effects

A

anemia, thrombocytopenia, neutropenia, increased risk of infection (monitor for infection for at least one year), allergic reactions including the bronchospasm and angioedema and GI discomfort

There is also some risk of secondary malignancy

50
Q

Brentuximab vedotin (Adcatris)

A

composed of a chimeric monoclonal antibody brentuximab, which is specific for CD30 molecules and is attached to an antimitotic agent monomethyl auristatin E

51
Q

Trastuzumab (Herceptin) administered with what other drugs

A

lapatinib or paclitaxel

52
Q

Ipilimumab (Yervoy) MOA

A

binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) which is expressed on the surface of helper T cells and transmits inhibitory signals to T cells. It is also found on regulatory T cells

CTLA-4 binds to CD80 and CD86 (B7) on antigen presenting cells
CTLA-4 regulates T cell responses in fighting disease

The antibody blocks the function of CTLA-4, resulting in a sustained immune response that attacks the cancer cells (Immune response will continue without stoping)

53
Q

Muromonab-CD3

A

100% mouse antibody

54
Q

Nivolumab (Opdivo) side effects

A

fatigue, shortness of breath, lack of appetite, GI symptoms, and musculoskeletal pain

55
Q

Natalizumab (Tysabri)

A

Humanized monoclonal antibody

56
Q

Bevacizumab (Avastin) MOA

A

directed against vascular endothelial growth factor (VEGF) receptors present on endothelial cells

VEFG promotes the proliferation of endothelial cells and formation of new blood vessels—inhibit formation of new blood vessels which will inhibit angiogenesis and the tumor dies

57
Q

Panitumumab (Vectibix)

A

Fully human monoclonal antibody (IgG2)

58
Q

Daclizumab (Zinbryta)

A

Humanized antibody

59
Q

omab

A

100% murine antibody

60
Q

Trastuzumab emtansine (Kadcyla) therapeutic uses

A

Specific for patients who are afflicted with HER2-positive metastatic breast cancer, and have been previously treated with Herceptin (NOT first line therapy)

patients who have already been treated for metastatic breast cancer or have re-developed tumor within six months of therapy

61
Q

Basiliximab (Simulect)

A

Chimeric monoclonal antibody

62
Q

Natalizumab (Tysabri) side effects

A

progressive multifocal leukoencephalopathy (PML), which is an opportunistic infection caused by John Cunningham (JC) virus

63
Q

Tocilizumab(Actemra) therapeutic uses

A

administered subcutaneously for moderate to severe rheumatoid arthritis and systemic juvenile idiopathic arthritis.
could be administered with or without methotrexate

64
Q

Ofatumumab (Arzerra) side effects

A

flu-like symptoms, upper respiratory infection, lower respiratory infection, rash, neutropenia and anemia

65
Q

Centuximab (Erbitux)

A

Chimeric monoclonal antibody (IgG1)

66
Q

Ixekizumab (Taltz) MOA

A

Inhibits IL-17A and IL-17A/F

IL-17 stimulates proliferation and activation of keratinocytes

67
Q

Ofatumumab (Arzerra) therapeutic uses

A

chronic lymphocytic leukemia which is refractory to fludarabine and Alemtuzumab

68
Q

Rituximab (Rituxan)

A

Chimeric monoclonal antibody

69
Q

Golimumab (Simponi) MOA

A

Inhibits tumor necrosis factor α, and used as an immunosuppressive drug

70
Q

Ixekizumab (Taltz) CI with what infection

A

Tuberculosis

71
Q

Bevacizumab (Avastin)

A

Humanized monoclonal antibody (IgG1)

72
Q

Trastuzumab (Herceptin) therapeutic uses

A

aggressive metastatic breasts cancer who over express HER-2

73
Q

Reslizumab (Cinqair) side effects

A

anaphylactic reaction, chest tightness, wheezing, light- headedness, itches, and rash

74
Q

Trastuzumab (Herceptin) side effects

A

development of ventricular dysfunction and congestive heart failure—left ventricular function must be evaluated in all patients before and during trastuzumab therapy

Patients treated with trastuzumab exhibit symptoms of cardiac dysfunction, dyspnea, peripheral edema and reduced ejection fraction.
In combination with anthracyclin and cyclophosphamide it exhibits severe cardiomyopathy.

It may cause allergic reactions, anaphylaxis and pulmonary events. Chills and fever have also been reported after first infusion.

75
Q

Golimumab (Simponi) therapeutic uses

A

administered once a month subcutaneously for the treatment of moderate to severe rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and ulcerative colitis(in adults)

76
Q

Vedolizumab(Entyvio) administration

A

Zero, two, and six weeks and then every 8 weeks

77
Q

Alemtuzumab (Lematrada) MOA

A

binds CD52 receptor which is present on the surface of normal and malignant T cells—It mediates its effects via antibody-dependent lysis of target cells (T cells) after binding to CD52 receptors (also neutralizes T cells)

CD52 is not present on erythrocytes (RBC)

78
Q

Golimumab (Simponi)

A

Human monoclonal antibody

79
Q

Ibritumomab (Zevalin) MOA

A

IgG1 conjugated to a linker—one of the two radiation sources Indium-111 or Yttrium-90

The antibody is directed against CD20 receptor which is not shed from the cell surface and is not internalized after binding to the antibody
The antibody is supplied in two vials one containing antibody conjugated to Indium-111 and the other to Yttrium-90.

After binding to cells expressing CD20 receptors the antibody delivers radiation which enhances its killing effect and induces apoptosis and the radiation causes further damage to the cells by the formation of the free radicals

The B cells recover in about 9 months since CD20 receptor is not expressed on B cell precursors

80
Q

Alemtuzumab (Lematrada)

A

Humanized antibody (CDR grafted IgG1)

81
Q

Vedolizumab(Entyvio) therapeutic uses

A

ulcerative colitis and inflammatory disease

Used in patients who do not respond well to anti-TNFα therapies

82
Q

Certolizumab (Cimzia) therapeutic uses

A

RA and Chron’s

83
Q

Vedolizumab(Entyvio) MOA

A

Inhibits integrin α4β7 (LPAM-1, lymphocyte Peyer’s patch adhesion molecule 1)

Inhibiting the function of integrin α4β7 activity causes anti-inflammatory effect

84
Q

Natalizumab (Tysabri) therapeutic uses

A

Multiple sclerosis and Chron’s

lesions in multiple sclerosis are caused by T lymphocytes passing through the blood-brain barrier through their interaction with the adhesion molecules on endothelial cells (high endothelial venules)

By inhibiting the adhesion molecules, we block the migration of cytotoxic and inflammatory cells into the brain or the bowel/GI tract

85
Q

Certolizumab (Cimzia) side effects

A

decrease body’s ability to fight infection and increase the risk of serious or life-threatening infections, including severe bacterial, fungal, and/or viral infections.
GI discomfort, intestinal obstruction, diarrhea, upper respiratory infection, urinary tract infection, and arthralgia

86
Q

Adalimumab (Humira) MOA

A

binds to TNF alpha and blocks its interaction with p55 and p75 cell surface TNF alpha receptors

Modulates biological responses that are induced or regulated by TNF alpha including the changes in the levels of the adhesion molecules

Rapidly decreases acute phase proteins, serum cytokines, and metalloproteinase

87
Q

Adalimumab (Humira) cannot be given with what other drugs

A

TNF alpha inhibitors

88
Q

ximab

A

Chimeric antibody

89
Q

Infliximab (Remicade) therapeutic uses

A

treat rheumatoid arthritis and Crohn’s Disease and it may alter other immune cells

90
Q

Belimumab (Benlysta) MOA

A

inhibits B cell activating factor. B-cell (BAFF) also referred to as B-lymphocyte stimulator, is responsible for the development and survival of B cells (inhibit production of antibodies)

91
Q

Ofatumumab (Arzerra) MOA

A

specific for CD20 protein—its epitope is distinct from rituximab
Inhibits early stage B cell activation and cytotoxic to cells expressing CD20 (ADCC)

92
Q

Basiliximab (Simulect) MOA

A

binds to IL-2 receptor alpha chain (CD-25 antigen) on the surface of activated T lymphocytes (IL-2 receptor alpha chain are the high affinity receptors)

inhibits IL-2 mediated activation of T cells

While in circulation it impairs the response of the immune system to the antigenic challenge

93
Q

Adalimumab (Humaria) therapeutic use

A

Treat RA and Chron’s disease

94
Q

Palvizumab (Synagis)

A

CDR grafted antibody

95
Q

Rituximab (Rituxan) side effects

A

Most side effects are felt after the first treatment—immediate side effects include fever, chills and respiratory symptoms; other infusion reactions include nausea, angioedema, headache, hypertension, puritus, uticaria, rash and vomiting

96
Q

Ustekinumab (Stelara) MOA

A

Inhibits p40 subunit of the IL-12 and IL-23 cytokines.

IL-12 is also known as natural killer stimulatory factor or cytotoxic lymphocyte maturation factor. This cytokine is made up of a 40 kDA and a 35 kDA subunit—IL-12 p40 subunit is shared by IL-23.
• IL-23 plays an important role in inflammatory response
• In conjunction with other cytokines (IL-6, TGFβ) IL-23 stimulates naïve CD4+ T cells to differentiate into TH17 cells and TH22 cells, which are distinct from TH1 and TH2 cells.

TH17 cells promote the production of IL-17 which is a pro-inflammatory cytokine that enhances T cell priming and enhance the production of IL-1, IL-6, TNFα, and chemokines

97
Q

Ixekizumab (Taltz) side effects

A

flu like symptoms, infection, pain at the site of injection, nausea, and oropharyngeal pain

98
Q

Alirocumab (Praluent)

A

Human monoclonal antibody

99
Q

Centuximab (Erbitux) side effects

A

immunogenecity, electrolyte depletion and infusion reactions

100
Q

Nivolumab (Opdivo) MOA

A

It blocks immune checkpoint (immunologic brake) PD-1 (Programed death-1) (PD-1 receptor is present on T cells and B cells)
It blocks the activation of PD-1 receptors through their ligand, PD-L1–Binding of PD-L1 to PD-1 receptors causes the inhibition of T cells
PD-1, then allows the immune response to be produced in the closed vicinity of the tumor

Immune checkpoint—functions as a negative feedback for immune response (downregulate immune response)
Inhibit T cell function in secondary lymphoid organs and enhance the function of regulatory T cells

Antibody itself is not treating the disease—it is inhibiting the immune checkpoint to allow the immune response to continue without any inhibition

101
Q

Belimumab (Benlysta) side effects

A

nausea, diarrhea, fever, hypersensitivity, and infusion-site reactions, increased risk of infection

102
Q

Belimumab (Benlysta)

A

Human monoclonal antibody

103
Q

MOA of Alirocumab (Praluent)

A

Inhibits PCSK9 which will inhibit degradation of LDL receptors and increase removal of LDL cholesterol from circulation

104
Q

Vedolizumab(Entyvio)

A

Humanized antibody

105
Q

Infliximab (Remicade) side effects

A

Infection, cough, back pain, nausea, vomiting

106
Q

Reslizumab (Cinqair) therapeutic uses

A

Severe asthma and the eosinophilic phenotype (latest onset and very severe)
NOT used for an acute asthma attack

107
Q

Adalimumab (Humira) side effects

A

Infections, neurologic events and malignancies

108
Q

Ipilimumab (Yervoy) therapeutic uses

A

Malignant melanoma

109
Q

Adalimumab (Humira)

A

Human antibody

110
Q

Alirocumab (Praluent) therapeutic uses

A

second line treatment to reduce LDL cholesterol levels and used in patients who do not respond well to diet, exercise, statins or are intolerant to statins

111
Q

zumab

A

Humanized (human like) or CDR grafted antibody

112
Q

Abciximab (Centorex, Reopro)

A

Chimeric monoclonal antibody

113
Q

Vedolizumab(Entyvio) side effects

A

Flu like symptoms, GI problems, liver dysfunction, pain and swelling

114
Q

Reslizumab (Cinqair) MOA

A

Inhibits IL-5

IL-5 is responsible for the proliferation, maturation, differentiation, and effector function of eosinophils)

115
Q

Golimumab (Simponi) CI with what other drugs

A

abatacept
kineret
other TNFα blockers

116
Q

Trastuzumab (Herceptin) MOA

A

Binds to human epidermal growth factor type 2 receptor protein (HER-2). HER are transmembrane tyrosine kinase receptors involved in cell growth, differentiation and proliferation of epithelial cells and cytoblasts

mutation in the HER-2 receptor causes an increased amount of the growth factor receptor protein on the tumor cell surface which increases proliferation of the cells

inhibits the proliferation of tumor cells over expressing HER-2–causes HER-2 receptor down regulation by binding to the receptor and causing endocytosis of some receptors as well as limiting the signal for cell growth.

Fc region causes lysis via antibody-dependent cell-mediated cytotoxicity

117
Q

Bevacizumab (Avastin) therapeutic uses

A

In combination with a standard chemotherapeutic regimen (5-fuouracil-based) it is used for the treatment of patients with malignant colon or rectal cancer

Some forms of renal, ovarian, lung, and brain cancers

118
Q

Rituximab (Rituxan) therapeutic uses

A

Non-Hodgkin’s lymphoma.

Fifty percent of the patients have responded to the treatment with full or partial remission

119
Q

Alemtuzumab (Lematrada) therapeutic uses

A

multiple sclerosis and tissue transplantation