McPhail Exam 4 Flashcards
(130 cards)
1
Q
Mechanism of methotrexate
A
inhibits dihydrofolate reductase, which is involved in the de novo synthesis of thymine. Also causes the release of adenosine into the bloodstream and tissues, which has anti-inflammatory effects
2
Q
Methotrexate interaction
A
NSAIDs increase the blood concentrations of methotrexate
3
Q
What is the active metabolite of leflunomide
A
A77 1726
4
Q
A77 1726 mechanism
A
inhibits dihydro-orotate dehydrogenase, which is required for pyrimidine biosynthesis. It also inhibits tyrosine kinase, which would interfere with T and B cell proliferation. The cells become non-responsive to cytokines and inflammatory signals.
5
Q
Thalidomide mechanism
A
reported to decrease circulating TNF-a in patients with erythema nodosum leprosum but increase it in patients who are HIV seropositive
6
Q
Methotrexate indication
A
Rheumatoid arthritis
7
Q
Leflunomide indication
A
Rheumatoid arthritis
8
Q
Thalidomide indication
A
erythema nodosum
9
Q
Echinacea mechanism
A
has no direct antibacterial activity, but stimulates the innate immune system by increasing phagocytosis and the release of TNFs and interferons from macrophages and T cells
10
Q
Levamisole class
A
Immunorestorative agents/immunostimulants
11
Q
Levamisole mechanism
A
Mimics thymic hormone thymopoietin, which is probably why it’s effective. Restores depressed immune function of B cells, T cells, monocytes, and macrophages caused by chemotherapy.
12
Q
Imiquimod mechanism
A
toll like receptor 7 agonist that stimulates the immune system to produce interferon-α and other cytokines (IL-1,6,8,10,12, TNF-α) and activates macrophages, NK cells, TH¬1 cells, and B cells
13
Q
Vaccine definition
A
suspensions of attenuated or dead microorganisms administered for prevention amelioration, or treatment of infectious diseases
14
Q
What type of T cells do vaccines stimulate
A
TH2
15
Q
Killed (inactivated) pathogens
A
denaturing disinfectant kills pathogen, allows recovery of the surface antigens, but this risks losing antigenicity
16
Q
Live/attenuated pathogens
A
pass the pathogen through many generations of host animals to yield low virulent strain. Some viruses are too dangerous even at low virulence and they can regain virulence.
17
Q
Live/attenuated related strain
A
cowpox virus used in place of smallpox virus
18
Q
Cellular antigen from a pathogen
A
isolate the surface antigen from the pathogen, purify it and reconstitute into a vaccine preparation
19
Q
Genetically engineered pathogens
A
clone a piece of DNA encoding the surface antigen from the pathogen and over produce the antigen. This way you don’t have to expose workers to the pathogen and lower risk.
20
Q
Simple vaccine
A
contains only one kind of antigen or strain
21
Q
Multivalent vaccine
A
contains two or more kinds of antigens or strains that cause the same disease
22
Q
Polyvalent vaccine
A
contains two or more kinds of antigens or strains that cause different diseases
23
Q
Single-dose vaccine
A
needed only once during lifetime
24
Q
Multiple-dosing regimen
A
several doses needed to get full protection
25
Booster dose
needed to bolster/reinforce protection after some time
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Co-administered vaccine
only if they don’t interfere with each other
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Viral vaccines examples
smallpox, influenza, polio, chickenpox, rubella, hepatitis, measles, rotavirus, mumps, HPV
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Bacterial vaccines examples
pertussis, tuberculosis, meningococcal, cholera, haemophilus influenza type B, pneumococcal
29
Toxoids
denatured pathogens the bacteria would produce
30
What are the two subtypes of antibodies?
immunoglobulins (polyclonal) and monoclonal antibodies
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What are the two major uses for antibodies in the treatment of human disease?
to neutralize and eliminate toxic molecules or to eliminate target cells
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What are the four ways antibodies can eliminate target cells?
antibody-mediated cell growth control (bound antibodies block binding of growth factors)
antibody-mediated reticuloendothelial clearance aka macrophage system (antibody-costed target cells can be engulfed by phagocytes)
complement-mediated cytotoxicity aka CMC (IgG and IgM binding to cells elicits complement, leading to the formation of a membrane attack complex)
antibody-dependent cell-mediated cytotoxicity aka ADCC (large cells can be killed by cytotoxic substances released by macrophages and killer cells)
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human immunoglobulin examples
rabies, tetanus, hepatitis B, rho
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Digibind origin
Fab fragment of the IgG isolated from sheep immunized against digoxin
35
Digibind mechanism
It tightly binds digoxin, shifting the equilibrium away from drug receptor complex formation
36
What are the two types of anti-thymocyte globulin and what is the difference?
Thymoglobulin is from rabbits
| Atgam is from horses
37
Indication for anti-thymocyte globulin
Rejection of transplanted kidney, aplastic anemia in patients who are not suitable for bone marrow transplant, interim treatment until bone marrow transplant
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anti-thymocyte globulin mechanism
depletes circulating T-lymphocytes by direct killing, blocks lymphocyte function by binding to cell surface molecules involved in the regulation of cell function, which suppresses the cascade of immune cells.
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monoclonal antibody definition
an antibody synthesized from a single clone of B-lymphocytes or plasma cells
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polyclonal antibody definition
multiple immunoglobulins responding to different epitopes on an antigen molecule
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chimeric antibody
66% human
| constant region from human, antigen-binding region from mouse
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humanized antibody
>90% human
| only specific antigen binding sites (sugar fragments) from mice
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How do we make chimeric/humanized/fully human antibodies?
recombinant genetic engineering
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amab
rat
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emab
hamster
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imab
primate
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omab
mouse
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umab
human
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ximab
chimerized
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zumab
humanized
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Indication for MAbs that attach to a T cell receptor
used to stop rejection of transplanted organs
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What compounds did we cover that attach to a T cell receptor
muromonab-CD3 (OKT3), basiliximab, belatacept
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OKT3 generic
muromonab-CD3
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OKT3 mechanism of action
Interacts with the CD3 marker of human T cells and flags them for destruction. Decreases T cell numbers in the blood within minutes
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Basiliximab mechanism of action
binds to the IL-2 receptor of activated T cells as a competitive antagonist
56
Mechanism of action for belatacept
cytotoxic T lymphocyte associated antigen 4 (CTLA4) interrupts CD28 costimulation of T cell, resulting in an attenuation of interleukin 2 and interleukin 2 receptor (T cell anergy) and arrest of T cells at the G1 phase of the cell cycle (T cell apoptosis). Belatacept is a soluble recombinant fusion protein that mimics CTLA4
57
What MAbs did we cover for lymphomas?
rituximab, alemtuzumab, brentuximab vedotin, tositumomab I-131, and Y-90-labeled ibritumomab tiuxetan
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Indications for rituximab
cancer, follicular lymphoma, Wegener's granulomatosis, and microscopic polyangiitis
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Rituximab mechanism of action
binds to CD20, which is distributed on more than 90% of B cell non-Hodgkin's lymphomas but also present on normal B cells. However, since the cancer results in an overproduction of B cells, more of them are wiped out than the normal B cells.
60
Indication and target for alemtuzumab
indication: B-cell chronic lymphocytic leukemia
target: CD52
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Bentuximab vedotin indication
Hodgkin's lymphoma and systemic anaplastic large cell lymphoma
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Three components of bentuximab vedotin
The chimerized IgG1 antibody cAC10, specific for human CD30
The microtubule disrupting agent MMAE
A protease-cleavable linker that covalently attaches MMAE to cAC10
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Bentuximab vedotin mechanism of action
CD30 is prevalent in HL and sALCL but has limited expression in healthy cells. Binding of brentuximab to CD30 on the cell surface initiates internalization of the ADC-CD30 complex. Inside the cell, MMAE is released via proteolytic cleavage. Binding of released MMAE to tubulin disrupts the microtubule network, which interferes with cell division, inducing apoptotic cell death.
64
Tositumomab I-131 target
CD20
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Tositumomab mechanism of action
induces normal immunological reactions and radioimmunoconjugates deliver cytotoxic ionization radiation. High energy beta particles emitted by I-131 are cytotoxic over distances of about 1-2mm, therefore also kills cells that are inaccessible to the antibody.
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Y-90-labeled ibritumomab tiexetan target
CD20
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HER2
an oncogene in breast cancer that stimulates cell division
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Anti-HER2 MAbs
Tratuzumab, Ado-tratuzumab emtansine
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Trastuzumab mechanism of action
Anti-HER2 antibodies inhibit HER2-mediated signaling in cancer cells by blocking the extracellular receptor of HER2/neu, ultimately upregulating the levels and activity of p27 (Kip1) protein (an important cell dependent kinase (Cdk) inhibitor), which leads to cell cycle G1 arrest and growth inhibition.
At least six signaling targets and pathways are modulated by trastuzumab
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mechanism of emtansine/DM1
a maytansinoid that disrupts microtubule function
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MAbs that bind to epidermal growth factor receptor
Cetuximab, panitumumab
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Indication for cetuximab and panitumumab
EGFR expressing metastatic colorectal cancer (after disease progression following all available chemotherapy regimens).
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cetuximab and panitumumab mechanism of action
prevents ligand binding at the epidermal growth factor receptor, which inhibits cancer cell growth
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MAbs for rheumatoid arthritis and Crohn's disease
infliximab, adalimumab, tocilizumab, etanercept
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Infliximab mechanism of action
binds to both free and membrane bound TNF-α. Blocking TNF-α slows the progression of the disease
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infliximab indications
rheumatoid arthritis, Crohn’s disease, and ankylosing spondylitis
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adalimumab target
TNF-alpha
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tocilizumab target
IL-6 receptor
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etanercept mechanism of action
binds TNF-α, slowing down/stopping joint damage by preventing it from binding to immune cells
80
MAbs for asthma and allergic rhinitis
omalizumab, mepolizumab
81
omalizumab mechanism of action
selectively binds to circulating IgE, so prevents binding of IgE to mast cells and other effector cells. Without surface-bound IgE, these cells are unable to recognize allergens, so prevents cellular activation by antigens and the subsequent allergic reactions
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mepolizumab target
IL-5 receptor on eosinophils
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efalizumab indication
psoriasis
84
efalizumab mechanism of action
Inhibits the interaction of CD11a (LFA-1) with various ICAM molecules. Because ICAM-1 (CD54) is expressed on activated endothelial cells and antigen presenting cells (APCs), the antibody inhibits both the APC-T cell interaction and the T cell adhesion to endothelial cells, preventing trans-endothelial migration so immune cells can’t get into the tissues
85
Interferon alpha 2b indications
Hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposi’s sarcoma, chronic hepatitis B, Roferin-A also has the indication of Chronic Granulomatous Disease
86
Interferon beta-1a indications
neurological exacerbations in relapsing-remitting multiple sclerosis
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Interferon beta-1b indications
neurological exacerbations in relapsing-remitting MS
88
How does commercial IL-2 differ from natural IL-2
commercial IL-2 differs from native IL-2 in that it’s not glycosylated, has no terminal alanine, and a serine is substituted for cysteine-125 (serine has an OH and cysteine has an SH)
89
IL-2 indications
cancer, especially metastatic renal cell carcinoma
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IL-11 indications
following myelosupressive chemotherapy in patients with nonmyeloid malignancies
91
Effects on anakinra
When given alone or in combination with methotrexate it improves clinical signs and symptoms, decreases radiographic progression, improves patient function, decreases pain and fatigue, and slows bone erosion and degradation of the joint.
92
Target for anakinra
blocks the binding of IL-1
93
growth factor definition
control the expansion, proliferation, and differentiation of myeloid cells
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G-CSF
granulocyte colony stimulating factor
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M-CSF
macrophage colony stimulating factor
96
GM-CSF
granulocyte macrophage colony stimulating factor
97
Multi-CSF
multi-lineage colony stimulating factor
98
EPO
erythropoietin
99
TPO
thrombopoietin
100
What produces/secretes CSFs
activated T cells or macrophages
101
What produces/secretes erythropoietin
endothelial cells and fibroblasts
102
What is the difference between filgrastim and pegfilgrastim?
pegfilgrastim has polyethylene glycol attached
103
mechanism of action of the G-CSF analogs
stimulates the bone marrow to produce more white blood cells
104
G-CSF analog examples
filgrastim, pegfilgrastim
105
G-CSF analog indication
neutropenia due to non-myeloid cancer chemotherapy or severe chronic neutropenia or after bone marrow transplant
106
G-CSF risk
could promote growth of malignant myeloid cells in blood cancers
107
GM-CSF examples
sargramostim, erythopoietin
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sargramostim indication
autologous bone marrow replacement
109
sargramostim mechanism
hastens myeloid reconstitution
110
epoetin alfa indications
kidney dialysis, chemotherapy in non-myeloid malignancies
111
Difference between epoetin alfa and darbepoetin alfa
Darbepoetin alfa differs from epoetin alfa by having two extra carbohydrate chains, which gives it greater metabolic stability – it has a three-fold longer half-life
112
Indications for darbepoetin alfa
anemia associated with chronic renal failure, cancer chemotherapy
113
induction of immunosuppression
Medications given immediately after transplantation in intensified doses for the purpose of preventing acute rejection (up to 30 days)
Not used for long-term for immunosuppressive maintenance
Includes methylprednisolone, atgam, thymoglobulin, OKT3, and basiliximab
114
maintenance of immunosuppression
Medications given before, during or after transplant with the intention to maintain them long-term
Maintenance immunosuppression does not include any immunosuppressive medications given to treat rejection episodes or for induction of immunosuppression
Includes prednisone, cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, or rapamycin
115
anti-rejection immunosuppression
Medications given for the purpose of treating an acute rejection episode during the initial post-transplant period or during a specific follow up period, usually up to 30 days after the diagnosis of acute rejection
Includes methylprednisolone, atgam, OKT3, thymoglobulin, and basiliximab
116
role of analgesics in treating RA
relieve pain
117
role of NSAIDs in treating RA
relieve pain and reduce inflammation
| *only stops the prostaglandin inflammation process, the other pathways keep going
118
role of steroids in treating RA
relieve pain and reduce inflammation
119
role of DMARDs in treating RA
reduce pain, swelling, and tenderness as well as slow joint damage
120
role of biologic medicines in treating RA
targeted treatment to relieve pain and swelling and slow joint damage
121
old treatment for RA
used to relieve symptoms until it got too bad then address the disease
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new treatment for RA
treat to stop it from progressing as far as the patient gets older
123
RA pathophysiology
Activated T cells stimulate macrophages and fibroblast-like synoviocytes. These generate proinflammatory mediators and proteases, which induces a synovial inflammatory response and destroys the cartilage and bone. Proinflammatory cytokines released by synovial macrophages include TNF-α, IL-1, 6, 12, 15, 18, and 23.
124
Biologic agents whose main indication is RA
infliximab, adalimumab, ankinra, rituximab, tocilizumab, etanercept
125
nonpharmacological treatments for RA
exercise, diet (less animal products and more leaves), stress reduction, physical therapy, and surgery
126
Medication based therapies for RA
NSAIDs, nonbiologic and biologic DMARDs, immunosuppressants, and corticosteroids
127
Comparison of DMARDs and biologics in regards to deliver method
DMARDs are usually oral, and methotrexate is usually given just once a week. Biologics are usually injected under the skin or given IV, and administration ranges from daily to monthly
128
Comparison of DMARDs and biologics in regards to drug target
DMARDs target the entire immune system, while biologics work by targeting specific steps in the inflammatory process.
129
Comparison of DMARDs and biologics in regards to response time
it can take months before it is known whether a DMARD is working. With biologics, results are likely seen within 4-6 weeks, after just a few treatments. In the meantime, an NSAID or a steroid medication may relieve pain and swelling.
130
Comparison of DMARDs and biologics in regards to risks
both DMARDs and biologics can increase risk for infections. Serious infections, such as pneumonia, are the biggest risk of taking a biologic.
