Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

IHO Week 4 > Immunosuppressives > Flashcards

Immunosuppressives Flashcards

1
Q

What are the three chemical types of immunosuppressives?

A
  1. Glucocorticoids
  2. Antibiotics
  3. Antibodies and fusion proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two glucocorticoids we need to know? What are they used for?

A
  • Dexamethasone
  • Prednisone
  • Treatment of cancers that express the requisite receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the two antibiotic immunosuppresives? What are they used for?

A
  • Cyclosporine
  • Tacrolimus
  • Used to prevent rejection following bone marrow transplantation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are other antibiotics that function as mTOR inhibitors?

A

Everlolimus, Temsirolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the five antibodies and fusion proteins? What are they used for?

A
  • Alemtuzumab
  • Denileukin Diftitux
  • Ibritumomab
  • Rituximab
  • Tositumomab
  • Used for special leukemia and lymphomas because they target unique CDs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the mechanism of action for glucocorticoids?

A
  • Naturally occurring compound is cortisol
  • Interfere with the concentration, distribution and function of leukocytes
  • –Inc. neutrophils, dec. T & B lymphocytes, monocytes, eosinophils and basophils
  • –End result is decrease in cytokine release, including DECREASES IN IL-2 and TNF-alpha
  • Decreases size of lymph nodes and spleen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are glucocorticoids used in cancer chemotherapy?

A

-Given at higher doses, using a “pulse” regimen (in comparison to their use with inflammatory disease like asthma, arthritis, lupus, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What specific type of cancer are glucocorticoids used for?

A

Those that express the requisite receptors (e.g. prednisone-sensitive lymphomas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What dosing is given for cancer cells?

A

Chemotherapy

-High dose, “pulse”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What dosing is given to suppress a normal immune system?

A

Immuno-suppression

-Low dose, continuous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are triggers from cell division and what type of cell division is there for cancer cells and for the normal immune system?

A

Cancer cells - Unstimulated, Random Cell Division

Normal Immune System - Cell division is triggered by a specific antigen and cell division is synchronized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are immunosuppressive antibiotics used for?

A
  1. Prevent rejection following bone marrow transplant

2. Angiogenesis inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What immunosuppressive antibiotics prevent rejection of bone marrow transplants?

A

Cyclosporine, Tacrolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What immunosuppressive antibiotics act as angiogenesis inhibitors?

A

Everolimus, Temsirolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What two pathways involved in cell proliferation are these immunosuppressive antibiotics involved in?

A
  1. NFAT-mediated regulation of interleukin synthesis

2. mTOR regulation of cell growth and angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the MOA for immunosuppressive antibiotics?

A

Interfere with intracellular processes that are key for cell proliferation and cytokine production and release

  1. The 1st step in the process that leads to IL-2 mediated cell proliferation is activation of receptor tyrosine kinases (RTKs)
  2. Immunosuppressive antibiotics do not interfere with this process; they interfere with one of two intracellular signaling cascades
17
Q

What are the two intracellular signaling cascades immunosuppressive antibiotics interfere with?

A
  • Antirejection

- Anti-angiogeneis and anti-proliferation

18
Q

How does antirejection occur with immunosuppressive antibiotics?

A

-Binds to cytoplasmic proteins and inhibit calcineurin
–Cyclosporine binds to cyclophilin
–Tacrolimus binds to FK-binding protein
Calcineurin is necessary for activation of NFAT, a T cell specific transcription factor that is involved in the synesis of interleukins by activated T cells –> decreased release of IL-2 –> decreased activation of IL-2 receptor –> decreased cell proliferation

19
Q

How does anti-angiogenesis and anti-proliferation occur with immunosuppressive antibiotics?

A
  • Receptor tyrosine kinases can also increase expression of mTOR, an intracellular signaling molecule that increases cell division, increases bioenergetics and facilitates angiogenesis in many cell types
  • EVEROLIMUS and TEMSIROLIMUS also function as mTOR inhibitors
20
Q

What are the 5 antibodies and fusion proteins?

A
  1. Alemtuzumab
  2. Denileukin Diftitux
  3. Ibritumomab
  4. Rituximab
  5. Tositumomab
21
Q

What types of antibodies have been designed to selectively recruit the immune system to destroy cancer cells?

A
  • Ones that target CDs (CD 20 in NHL, and CD52 in B-CLL)

- Ones that target cell surface proteins (HER2, VEGF, EGFR) that are overexposed in specific cancers

22
Q

What are general concepts of antibodies and fusion proteins?

A
  • Typically prescribed when traditional chemotherapy has failed or when patient factors (esp. age) prevent the use of cytotoxic drugs
  • Goal is to get the immune system to recognize, and kill the cell that is expressing antigen
  • –Use immune system to suppress itself
23
Q

What is the Target & Use of Rituximab, Ibritumomab (90Y), and Tositumomab (131I)?

A

Target - CD20

Use - B cell non-hodgkin lymphoma (NHL)

24
Q

What is the Target & Use of Alemtuzumab?

A

Target - CD52

Use - B cell chronic lymphocytic leukemia (B-CLL)

25
Q

What is Denileukin Diftitux? How does it work? What is it used for?

A
  • Fusion protein that has diphtheria toxin coupled to IL-2
  • –Diptheria toxin catalyzes the ADP-ribosylation of elongation factor-2 –> inhibits protein translation by inactivating EF2
  • Goal is to kill cells expressing IL-2 receptors (activated T-lymphocytes, B lymphocytes and macrophages)
  • Approved for use in cutaneous T-cell lymphoma
26
Q

What resistance has developed against antibodies and fusion proteins?

A

-Changes in target protein that prevent the antibody from recognizing its antigen

27
Q

What are the pharmacokinetics of antibodies and fusion proteins?

A
  • IV admin.

- Long half-lives - detectable at least 3-6 months after completion of treatment

28
Q

What toxicities are common to all antibodies?

A
  1. Infusion reactions (77% of patients on rituximab)
  2. Other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis
    - Mouse (MO)&raquo_space; chimeric (XI) > humanized (ZU) for HAMA reaction
  3. Infections - esp. reactivation of tuberculosis
    - -Unknown effects on immunization, carcinogenesis, mutagenesis, impairment of fertility, pregnancy, nursing infants (human IgG is secreted in milk)
29
Q

What toxicities are specific for anti-CD antibodies?

A
  • Cardiac arrhythmias
  • Tumor lysis syndrome
  • ALEMTUZUMAB: cough, tightness in chest
  • Suspicion that radiolabelled antibodies (IBRITUMOMAB, TOSITUMOMAB) may be more likely to cause birth defects (this hasn’t been tested!)

IHO Week 4 (25 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions