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IHO Week 5 (MJ) > Immunosuppressive Drugs > Flashcards

Immunosuppressive Drugs Flashcards

1
Q

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

A

organ transplantation
autoimmune disease
hypersensivity

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2
Q

Are primary or secondary immune responses more effectively suppressed?

A

Primary

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3
Q

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

A

before

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4
Q

Limitations of immunosuppressive therapy?

A

Increased risk of infection

Increased risk of lymphomas and malignancy

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5
Q

Major classes of immunosuppressive drugs?

A

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

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6
Q

What immunosuppressive drug is used for autoimmune disease?

A

prednisone

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7
Q

What immunosuppressive drug is used for autoimmune hemolytic anemia?

A

Prednisone

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8
Q

Acute glomerulonephritis treatment?

A

Prednisone

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9
Q

Autoreactive tissue disorder treatmetn?

A

Predinisone

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10
Q

Organ transplant drug?

A

Cyclosporine

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11
Q

2 classes of steroids synthesized by the adrenal cortex

A

corticosteroids (21C)

androgens (19C)

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12
Q

2 classes of corticosteroids

A

Glucocortiocoids

mineralocorticoids

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13
Q

main glucocorticoid in humans?

A

hydrocortisone (cortisol)

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14
Q

main mineralocorticoid in humans?

A

aldosterone

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15
Q

corticosteroids are secreted in response to _______

A

ACTH (adrenocorticotrophic hormone)

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16
Q

Are glucocorticoids or mineralocorticoids anti inflammatory?

A

glucocortiocids

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17
Q

Inhaled glucocorticoid benefit?

A

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

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18
Q

Where are glucocorticoids absorbed? Excreted?

A

Liver; Kindey

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19
Q

Synthetic steroids list

A

Betamethasone
Dexamethasone
Methylprednisolone
Prednisone

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20
Q

SE of large dose steroids?

A

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

21
Q

Symptoms of acute renal deficiency?

A 
fever
myalgia
arthralgia
malaise
death can occur with hypotension and shock
22
Q

Calcineurin inhibitors

A

Cyclosporine

Tacrolimus

23
Q

Cyclosporine

A

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

24
Q

Long term therapy for transplantation?

A

Cyclosporine

25
Q

Major adverse effect of cyclosporine

A

renal toxicity

26
Q

Tacrolimus (FK506)

A

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.

27
Q

Toxicity of Tacrolimus

A

Nephrotoxic

28
Q

Sirolimus

A

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

29
Q

Toxicity of Sirolimus (rapamycin)

A

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

30
Q

Sirolimus prevents clonal expansion of…

A

both B and T lymphocytes

31
Q

Mycophenolate Mofetil

A

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

32
Q

Toxicity of Mycophonolate Mofetil

A

Hematologic and gastrointestinal.

Leukopenia, diarrhea, vomitting

33
Q

Immune proliferation vs. cancer proliferation

A

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

34
Q

Why is the synchronization of immune proliferation advantageous?

A

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

35
Q

Anti-thymocyte globulin (ATG)

A

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

36
Q

Toxicity of ATG

A

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

37
Q

Muromonab-CD3

A

Acute kindney, heart, liver rejection prevention.

38
Q

Muromonab-CD3 mechanism

A

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

39
Q

Cytokine release syndrome

A

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

40
Q

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

A

Give glucocorticoids

41
Q

Daclizumab or Basiliximab

A

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.

42
Q

Toxicity of Daclizumab/Basiliximab

A

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

43
Q

SOA of Glucocorticoids

A

Glucocorticoid response elements in DNA (regulate gene transcription)

44
Q

SOA Muromonab-CD3

A

T cell receptor complex (blocks antigen recognition)

45
Q

SOA Cyclosporine

A

Calcineurin (inhibits phosphatase activity)

46
Q

SOA Tacrolimus

A

Calcineurin (inhibits phosphatase activity)

47
Q

Mycophenolate mofetil

A

Inosine monophosphate dehydrogenase (inhibits activity)

48
Q

Daclizumab

Basiliximab

A

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

49
Q

Sirolimus

A

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

IHO Week 5 (MJ) (4 decks)

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