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POD Exam 4 > Immunopharmacology > Flashcards

Immunopharmacology Flashcards

1
Q

Name two limitations of therapy

A

Increased risk of:

  • infection
  • lymphomas and related cancers
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2
Q

SOA:

Glucocorticoids

A

Glucocorticoid response elements in DNA (regulate gene transcription)

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3
Q

SOA:

Muromonab-CD3

A

T-cell receptor complex (blocks Ag recognition)

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4
Q

SOA:

Cyclosporine

A

Calcineurin (inhibits phosphatase activity)

- cyclophilin

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5
Q

SOA:

Tarcrolimus

A

Calcineurin (inhibits phosphatase activity)

- FKBP

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6
Q

SOA:

Azathioprine

A

Deoxyribonucleic acid (false nucleotide incorporation)

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7
Q

SOA:

Mycophenolate Mofetil

A

Inosine monophosphate dehydrogenase (inhibits activity)

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8
Q

SOA:

Daclizumab, Basiliximab

A

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

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9
Q

SOA:

Sirolimus

A

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

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10
Q

What does immunosuppressive drugs target?

A

T-cell Activation

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11
Q

MOA:

Cyclosporine

A

binds cyclophilin A (in cytoplasm) in T-cells –> complex –> binds and inhibits calcineurin + mediated activities:

synthesis of IL-2, IL-2R, protooncogenes

increase TGF-beta production

affects proliferation

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12
Q

Uses:

Cyclosporine, Tacrolimus, Sirolimus, Everolimus

A

prevention/treatment of organ rejection (+/- corticosteroids)

Autoimmune disorders

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13
Q

Toxicity:

Cyclosporine

A
  • Nephrotoxicity
  • Hypertension (esp in renal and cardiac transplant)
  • Hepatotoxicity
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14
Q

MOA:

Tacrolimus

A

Binds FK506 binding protein-12 (FKBP) (cytoplasmic protein)

inhibits calcineurin + mediated activities:

synthesis of IL-2, IL-2R, protooncogenes

affects proliferation

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15
Q

Which drug is more potent: Cyclosporine vs Tarcrolimus?

A

Tacrolimus

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16
Q

Toxicity:

Tacrolimus

A
  • Nephrotoxicity
  • Neurotoxicity*
  • hypertension
  • diabetes*

*different from cyclosporine

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17
Q

MOA:

Sirolimus and Everolimus

A

Binds FKBP (like Tacrolimus) and inhibits mTOR

Blocks T-cell cycle at the G1 –> S transition

Affects proliferation

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18
Q

How are Sirolimus/Everolimus and Tacrolimus similar/different?

A

Both bind FKBP
Simlar uses

Tacrolimus inhibits Calcineurin
Sirolimus/Everolimus inhibits mTOR

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19
Q

What is mTOR?

A

kinase important for T cell proliferation

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20
Q

Toxicity:

Sirolimus, Everolimus

A
  • Inc in serum cholesterol + triglycerides
  • delay graft function
  • delay wound healing
  • Anemia, leukopenia, thrombocytopenia
  • Inc risk of infection
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21
Q

Example of Glucocorticoids

A

Prednisone

Prednisolone

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22
Q

MOA:

Glucocorticoid

A

Inhibit T-cell proliferation, T-cell dependent immunity, expression of genes encoding cytokines

T cells > B cells

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23
Q

Uses:

Glucocorticoids

A

prevent organ rejection - Anti-inflammatory

Autoimmune disease

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24
Q

What do Cytotoxic drugs affect? Are they selective or non-selective?

A

DNA synthesis

non-selective

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25
Q

Which drug is Cytotoxic?

A

Azathioprine

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26
Q

What metabolite does Azathioprine get converted into in vivo?

A

6-mercaptopurine

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27
Q

MOA:

6-mercaptopurine

A

inhibits purine biosynthesis –> eventually inhibits DNA synthesis –> inhibits T-cell proliferation

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28
Q

Uses:

Azathiorprine

A

adjunct for prevention of organ transplant

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29
Q

Drug intrxn:

Azathioprine

A

Allopurinol given for gout

reduce azathioprine

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30
Q

What does allopurinol inhibit? What does this enzyme do?

A

Xanthine oxidase

Catabolizes azathioprine metabolites

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31
Q

Toxicity:

Azathioprine

A

Bone marrow suppression - leukopenia, thrombocytopenia, anemia

Inc risk for infection

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32
Q

MOA:

Mycophenolate mofetil

A

Prodrug –> mycophenolic acid (MPA)

Affects B and T lymphocyte proliferation

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33
Q

What is Mycophenolic acid?

A

REVERSIBLE inhibitor of inosine monophosphate dehydrogenase (IMPDH)

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34
Q

What is the result of IMPDH inhibition?

A

inhibition of de novo synthesis of guanine nucleotide

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35
Q

B and T lymphocytes are selectively sensitive to ____ because they require IMPDH for ________ via _______

A

Mycophenolic acid

proliferation via de novo synthesis of guanine

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36
Q

Uses:

Mycophenolate mofetil

A
  • prophylaxis of transplant rejection
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37
Q

Toxicity:

Mycophenolate mofetil

A

GI effects

leukopenia

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38
Q

What decreases absorption of Mycophenolate mofetil ?

A

Antacids (Magnesium, Aluminum)

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39
Q

What do immunosuppresion Ab and fusion receptor proteins target? What is the clonality of the Abs? What are they used for?

A

lymphocyte cell surface Ags

Mostly monoclonal, one polyclonal

Prevention and treatment of organ transplant rejection

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40
Q

What is the one polyclonal Ab used for immunosuppression?

A

Antithymocyte globulin (ATGAM)

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41
Q

MOA:

Antithymocyte globulin

A

Binds CIRCULATING T lymphocytes

Induces lymphopenia (complement mediated) and decreases T-cell function

42
Q

Uses:

Antithymocyte globulin

A

Prevent AND Treat acute allograft rejection

43
Q

Toxicitiy:

Antithymocyte globulin

A
  • Serum sickness
  • Nephritis
  • Chills
  • Fever
  • Rash
44
Q

Muromonab-CD3 (Orthoclone) is a ______ Ab against _______

A

Monoclonal Ab

CD3 glycoprotein (associated with the T cell receptor complex)

45
Q

MOA:

Muromonab-CD3

A

Induces internalization of the T cell receptor complex

–> dec circulating T cells

46
Q

Use:

Muromonab-CD3

A

Reverse transplant rejection

47
Q

Adverse effects:

Muromonab-CD3

A
  • Cytokine release syndrome
  • Anaphylactic rxns
  • CNS toxicity
  • Inc risk for infection and malignancy
48
Q

“humanized” monoclonal Abs

A 
Daclizumab and basiliximab
Alemtuzumab (Campath-1H)
Efalizumab 
Tocilizumab
Rituximab
49
Q

MOA:

Daclizumab and basiliximab

A

Binds IL-2R on T cells —> inhibits T cell activation via downregulation of IL-2R

50
Q

Use:

Daclizumab and basiliximab

A

PROPHYLAXIS of ACUTE REJECTION in RENAL transplantation

51
Q

MOA:

Alemtuzumab (Campath-1H)

A

Binds CD52 glycoprotein on:

B cells, T cells, monocyes, macs, NK cells

Induces lympholysis

52
Q

What is lympholysis ?

A

Profound depletion of T cells - apoptosis mediated

53
Q

Use:

Alemtuzumab (Campath-1H)

A

Chronic lymphocytic leukemia

54
Q

MOA:

Efalizumab

A

Binds CDIIa subunit of LFA-1 protein on T and B cells

–> inhibits interaction between LFA-1 and ICAM-1

–> inhibits T cell adhesion and activation

55
Q

Use:

Efalizumab

A

Prevent organ transplant rejection

Treat psoriasis

56
Q

MOA:

Tocilizumab

A

Binds IL-6R and inhibits IL-6 action

57
Q

Use:

Tocilizumab

A

Juvenile rheumatoid arthritis

58
Q

Adverse effects:

Tocilizumab

A

increases risk for infection

59
Q

MOA:

Rituximab

A

Binds CD20 on B lymphocytes –> induces B lymphocyte cell lysis

60
Q

Use:

Rituximab

A

Chronic lymphoid leukemia
Non-hodgkin’s lymphoma
Rheumatoid arthritis

61
Q

Which monoclonal Immunosuppression Ab is not humanized?

A

Muromonab-CD3 (Orthoclone)

62
Q

What are 3 Anti-TNF drugs?

A

Infliximab
Adalimumab
Etanercept

63
Q

Which Anti-TNF drug is humanized? Mouse-human? fusion protein?

A

Adalimumab - humanized

Infliximab - mouse/human

Etanercept - fusion protein

64
Q

Etanercept is a fusion protein consisting of the ligand binding domain of ____ receptor fused to ____ fragment

A

TNF

IgG1

65
Q

MOA:

Infliximab
Adalimumab
Etanercept

A

Bind circulating TNF –> NEUTRALIZES TNF activity

66
Q

Use:

Infliximab
Adalimumab
Etanercept

A

Rheumatoid arthiritis
Psoriasis
Crohn’s disease

67
Q

Toxicity:

anti-TNF drugs

A

Inc risk for infection, lymphomas and other cancer

68
Q

MOA:

Alefacept

A

binds CD2 on T cells

–> inhibits interaction between LFA-3 and CD-2 —> inhibits T cell adhesion and activation

69
Q

What type of fusion protein is Alefacept?

A

LFA-3 - IgG1

70
Q

Use:

Alefacept

A

Treat psoriasis

71
Q

What can be targeted in order to inhibit T cell Activation?

A

T-cell Co-stimulation

interaction: CD80/CD86 (APC) : CD28 (T cell)

72
Q

MOA:

Abatacept/Belatacept

A

binds CD80/CD86 on APC cells –> INHIBITS CO-STIMULATORY pathway

73
Q

What type of fusion proteins are Abatacept/Belatacept?

A

CTLA-4 - IgG1

74
Q

Use:

Abatacept?
Belatacept?

Toxicity?

A

Abatacept: treatment for juvenile idiopathic arthritis and Rheumatoid arthritis

Belatacept: prevent organ transplant rejection

  • both inc risk for infection
75
Q

What are immunostimulants used to treat? (2)

A
  • Immunodeficiency

- bolster immunity against specific targets

76
Q

Do immunostimulants act through cellular or humoral immunity?

A

Either one or BOTH

77
Q

Magnitude of stimulation by immunostimulants can be highly ____

A

Variable

78
Q

Use of Immune globulin for passive immunity is (specific vs nonspecific)?

A

Nonspecific

contains all subclasses (IgG>IgM)

79
Q

When is specific immune globulins used?

A

used in various immunodeficiency states such as measles, HepA, Autoimmune hemolytic disease, tetanus, rabies

80
Q

What does BCG stand for? (vaccine)

A

Bacillus Calmette-Guerin

81
Q

What type of vaccine is BCG?

A

Live attenuated strain of Mycobacterium bovis

82
Q

What is the active component of BCG?

A

Muramyl dipeptide

83
Q

What does BCG stimulate?

A

NK cells and T cell activity

84
Q

What is the primary use of BCG vaccine?

A

Treatment of bladder cancer

85
Q

Toxicity:

BCG vaccine

A

severe hypersensitivity reaction

Shock

86
Q

What are 3 synthetic agents that are used as immunostimulatory?

A

Levamisole
Isoprinosine
Thalidomide

87
Q

Immunostimulatory function of Levamisole?

A

Inhibits T-suppressor cells

used for colon cancer

88
Q

Immunostimulatory function of Isoprinosine?

A

Increase NK cell cytotoxicity and activity of T cells and monocytes

89
Q

Immunostimulatory function of Thalidomide?

A

Decrease circulating TNF-a

90
Q

What is Thalidomide used for?

A

Refractory arthritis

Erythema nodosum leprosum

91
Q

What is a contraindication of thalidomide?

A

Teratogenic properties in women who are pregnant or who may become pregnant

92
Q

Interferon alpha is part of _____ defense. It activates ____ (3 things).

A

antiviral

Macs, T lymphocytes, NK cells

93
Q

Use:

INF-a

A

Cancers

Hep B and C

94
Q

Is INF-a immunosuppresant or stimulant? IL-2?

A

both are immunostimulant

95
Q

Toxicity

INF-a

A

Flu like symptoms

Pulmonary hypertension

96
Q

MOA and Use:

IL-2

A

Activates cellular immunity

  • metastatic melanoma, renal cell carcinoma, AIDS ptns
97
Q

Toxicity:

IL-2

A

severe hypotension
Cardiovascular toxicity

Pulmonary Edema*** dose limiting

98
Q

What does Granulocyte colony stimulating factors do?

A

Stimulate inc in numbers of granulocytes and monocytes

99
Q

What produces glycoproteins (Granulocyte colony stimulating factors)?

A

Monocytes
Fibroblasts
Endothelial cells

100
Q

What are granulocyte colony stimulating factors used for?

A

reduce neutropenia (esp due to chemotherapy)

POD Exam 4 (3 decks)

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