Immunosuppressive Drugs

Question 1

Immunosuppressive drugs are most often used to dampen the immune system in…

Answer 1

organ transplantation
autoimmune disease
hypersensivity

Question 2

Are primary or secondary immune responses more effectively suppressed?

Answer 2

Primary

Question 3

The immune response is more likely to be inhibited if therapy is begun ______ exposure to the immunogen

Answer 3

before

Question 4

Limitations of immunosuppressive therapy?

Answer 4

Increased risk of infection

Increased risk of lymphomas and malignancy

Question 5

Major classes of immunosuppressive drugs?

Answer 5

Glucocorticoids (anti-inflammatory steroids)
Calcineurin Inhibitors
Antiproliferative/antimetabolic drugs
Antibodies

Question 6

What immunosuppressive drug is used for autoimmune disease?

Answer 6

prednisone

Question 7

What immunosuppressive drug is used for autoimmune hemolytic anemia?

Answer 7

Prednisone

Question 8

Acute glomerulonephritis treatment?

Answer 8

Prednisone

Question 9

Autoreactive tissue disorder treatmetn?

Answer 9

Predinisone

Question 10

Organ transplant drug?

Answer 10

Cyclosporine

Question 11

2 classes of steroids synthesized by the adrenal cortex

Answer 11

corticosteroids (21C)

androgens (19C)

Question 12

2 classes of corticosteroids

Answer 12

Glucocortiocoids

mineralocorticoids

Question 13

main glucocorticoid in humans?

Answer 13

hydrocortisone (cortisol)

Question 14

main mineralocorticoid in humans?

Answer 14

aldosterone

Question 15

corticosteroids are secreted in response to _______

Answer 15

ACTH (adrenocorticotrophic hormone)

Question 16

Are glucocorticoids or mineralocorticoids anti inflammatory?

Answer 16

glucocortiocids

Question 17

Inhaled glucocorticoid benefit?

Answer 17

designed for enhanced uptake and prolonged tissue binding in the airway, as well as nearly complete hepatic first pass inactivation

Question 18

Where are glucocorticoids absorbed? Excreted?

Answer 18

Liver; Kindey

Question 19

Synthetic steroids list

Answer 19

Betamethasone
Dexamethasone
Methylprednisolone
Prednisone

Question 20

SE of large dose steroids?

Answer 20

Increased susceptibility to infection (immunosuppression)
Peptic ulceration
behavioral disturbances
cataracts
osteoporosis and vertebral compression fractures
inhibiton of grow

Question 21

Symptoms of acute renal deficiency?

Answer 21

fever
myalgia
arthralgia
malaise
death can occur with hypotension and shock

Question 22

Calcineurin inhibitors

Answer 22

Cyclosporine

Tacrolimus

Question 23

Cyclosporine

Answer 23

Binds to cytoplasmic receptor protein cyclophilin (inhibits calcineurin activity)
This blocks dephosphorylation events critical for cytokine gene expression and t cell activation.

Question 24

Long term therapy for transplantation?

Answer 24

Cyclosporine

Question 25

Major adverse effect of cyclosporine

Answer 25

renal toxicity

Question 26

Tacrolimus (FK506)

Answer 26

binds to cytoplasmic receptor protein FKBP (FK506 binding protein), resulting in inhibition of calcineurin activity. This blocks dephosphorylation event critical for cytokine gene expression and t cell activation.

Question 27

Toxicity of Tacrolimus

Answer 27

Nephrotoxic

Question 28

Sirolimus

Answer 28

Binds FKBP to inhibit enzyme in cell cycle progression (mTOR). Blocks G1 to S phase.

Question 29

Toxicity of Sirolimus (rapamycin)

Answer 29

Dose dependent increases in cholesterol and triglycerides. nephrotoxic in combination with cyclosporine increased risk of lymphoma and infection CYP3A4

Question 30

Sirolimus prevents clonal expansion of...

Answer 30

both B and T lymphocytes

Question 31

Mycophenolate Mofetil

Answer 31

A metabolite is an inhibitor in inosine monophosphate dehydrogenase (IMPDH), an important enzyme in the de nova pathway of guanine nucleotide synthesis. B and T cells are highly dependent on this pathway for cell proliferation, while others use salvage pathways

Question 32

Toxicity of Mycophonolate Mofetil

Answer 32

Hematologic and gastrointestinal. | Leukopenia, diarrhea, vomitting

Question 33

Immune proliferation vs. cancer proliferation

Answer 33

immune proliferation is in response to a specific antigen and is synchronized. cancer proliferation is unstimulated. random and in an unsynchronized fashion.

Question 34

Why is the synchronization of immune proliferation advantageous?

Answer 34

If you know the time/stage of the cell cycle it is easier to target killing, and then continue with a continuous block.

Question 35

Anti-thymocyte globulin (ATG)

Answer 35

purified immunoglobin from animals purified with human thymocytes. Immunoglobulin binds in circulation and results in lymphopenia and impaired T cell immune responses.

Question 36

Toxicity of ATG

Answer 36

immunoglobulin is recognized as foreign resulting in serum sickness and nephritis. Anaphylaxis is rare.

Question 37

Muromonab-CD3

Answer 37

Acute kindney, heart, liver rejection prevention.

Question 38

Muromonab-CD3 mechanism

Answer 38

mouse monoclonal ab that binds to e chain of CD3. T cell receptor complex is internalized preventing further antigen recognition.

Question 39

Cytokine release syndrome

Answer 39

at the onset of muromonab treatment, mild flu like illness to life threatening shock

Question 40

What should one do to prevent cytokine release syndrome when initiating Muromonab-CD3?

Answer 40

Give glucocorticoids

Question 41

Daclizumab or Basiliximab

Answer 41

Anti-IL2 receptor (CD25) antibodies | Binds to IL-2 receptor present on activated, but not resting, T cells and blocks IL-2 mediated T cell activation events.

Question 42

Toxicity of Daclizumab/Basiliximab

Answer 42

No cytokine release syndrome. Lower incidence of lymphoproliferative disorders and opportunistic infection than other immunosuppressive drugs. Anaphylactic reactions may occur.

Question 43

SOA of Glucocorticoids

Answer 43

Glucocorticoid response elements in DNA (regulate gene transcription)

Question 44

SOA Muromonab-CD3

Answer 44

T cell receptor complex (blocks antigen recognition)

Question 45

SOA Cyclosporine

Answer 45

Calcineurin (inhibits phosphatase activity)

Question 46

SOA Tacrolimus

Answer 46

Calcineurin (inhibits phosphatase activity)

Question 47

Mycophenolate mofetil

Answer 47

Inosine monophosphate dehydrogenase (inhibits activity)

Question 48

Daclizumab | Basiliximab

Answer 48

IL-2 receptor (blocks IL-2-mediated T cell activation)

Question 49

Sirolimus

Answer 49

Protein kinase involved in cell cycle progression (mTOR) (inhibits activity)