Immunopharmacology Flashcards Preview

POD Exam 4 > Immunopharmacology > Flashcards

Flashcards in Immunopharmacology Deck (100):
1

Name two limitations of therapy

Increased risk of:

- infection
- lymphomas and related cancers

2

SOA:

Glucocorticoids

Glucocorticoid response elements in DNA (regulate gene transcription)

3

SOA:

Muromonab-CD3

T-cell receptor complex (blocks Ag recognition)

4

SOA:

Cyclosporine

Calcineurin (inhibits phosphatase activity)
- cyclophilin

5

SOA:

Tarcrolimus

Calcineurin (inhibits phosphatase activity)
- FKBP

6

SOA:

Azathioprine

Deoxyribonucleic acid (false nucleotide incorporation)

7

SOA:

Mycophenolate Mofetil

Inosine monophosphate dehydrogenase (inhibits activity)

8

SOA:

Daclizumab, Basiliximab

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

9

SOA:

Sirolimus

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

10

What does immunosuppressive drugs target?

T-cell Activation

11

MOA:

Cyclosporine

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

12

Uses:

Cyclosporine, Tacrolimus, Sirolimus, Everolimus

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

Autoimmune disorders

13

Toxicity:

Cyclosporine

- Nephrotoxicity
- Hypertension (esp in renal and cardiac transplant)
- Hepatotoxicity

14

MOA:

Tacrolimus

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

inhibits calcineurin + mediated activities:

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

affects proliferation

15

Which drug is more potent: Cyclosporine vs Tarcrolimus?

Tacrolimus

16

Toxicity:

Tacrolimus

- Nephrotoxicity
- Neurotoxicity*
- hypertension
- diabetes*

*different from cyclosporine

17

MOA:

Sirolimus and Everolimus

Binds FKBP (like Tacrolimus) and inhibits mTOR

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

Affects proliferation

18

How are Sirolimus/Everolimus and Tacrolimus similar/different?

Both bind FKBP
Simlar uses

Tacrolimus inhibits Calcineurin
Sirolimus/Everolimus inhibits mTOR

19

What is mTOR?

kinase important for T cell proliferation

20

Toxicity:

Sirolimus, Everolimus

- Inc in serum cholesterol + triglycerides
- delay graft function
- delay wound healing
- Anemia, leukopenia, thrombocytopenia
- Inc risk of infection

21

Example of Glucocorticoids

Prednisone
Prednisolone

22

MOA:

Glucocorticoid

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

T cells > B cells

23

Uses:

Glucocorticoids

prevent organ rejection - Anti-inflammatory
Autoimmune disease

24

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

DNA synthesis

non-selective

25

Which drug is Cytotoxic?

Azathioprine

26

What metabolite does Azathioprine get converted into in vivo?

6-mercaptopurine

27

MOA:

6-mercaptopurine

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

28

Uses:

Azathiorprine

adjunct for prevention of organ transplant

29

Drug intrxn:

Azathioprine

Allopurinol given for gout

reduce azathioprine

30

What does allopurinol inhibit? What does this enzyme do?

Xanthine oxidase

Catabolizes azathioprine metabolites

31

Toxicity:

Azathioprine

Bone marrow suppression - leukopenia, thrombocytopenia, anemia

Inc risk for infection

32

MOA:

Mycophenolate mofetil

Prodrug --> mycophenolic acid (MPA)

Affects B and T lymphocyte proliferation

33

What is Mycophenolic acid?

REVERSIBLE inhibitor of inosine monophosphate dehydrogenase (IMPDH)

34

What is the result of IMPDH inhibition?

inhibition of de novo synthesis of guanine nucleotide

35

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

Mycophenolic acid

proliferation via de novo synthesis of guanine

36

Uses:

Mycophenolate mofetil

- prophylaxis of transplant rejection

37

Toxicity:

Mycophenolate mofetil

GI effects
leukopenia

38

What decreases absorption of Mycophenolate mofetil ?

Antacids (Magnesium, Aluminum)

39

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

lymphocyte cell surface Ags

Mostly monoclonal, one polyclonal

Prevention and treatment of organ transplant rejection

40

What is the one polyclonal Ab used for immunosuppression?

Antithymocyte globulin (ATGAM)

41

MOA:

Antithymocyte globulin

Binds CIRCULATING T lymphocytes

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

42

Uses:

Antithymocyte globulin

Prevent AND Treat acute allograft rejection

43

Toxicitiy:

Antithymocyte globulin

- Serum sickness
- Nephritis
- Chills
- Fever
- Rash

44

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

Monoclonal Ab

CD3 glycoprotein (associated with the T cell receptor complex)

45

MOA:

Muromonab-CD3

Induces internalization of the T cell receptor complex

--> dec circulating T cells

46

Use:

Muromonab-CD3

Reverse transplant rejection

47

Adverse effects:

Muromonab-CD3

- Cytokine release syndrome
- Anaphylactic rxns
- CNS toxicity
- Inc risk for infection and malignancy

48

"humanized" monoclonal Abs

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

49

MOA:

Daclizumab and basiliximab

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

50

Use:

Daclizumab and basiliximab

PROPHYLAXIS of ACUTE REJECTION in RENAL transplantation

51

MOA:

Alemtuzumab (Campath-1H)

Binds CD52 glycoprotein on:

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


Induces lympholysis

52

What is lympholysis ?

Profound depletion of T cells - apoptosis mediated

53

Use:

Alemtuzumab (Campath-1H)

Chronic lymphocytic leukemia

54

MOA:

Efalizumab

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

Use:

Efalizumab

Prevent organ transplant rejection

Treat psoriasis

56

MOA:

Tocilizumab

Binds IL-6R and inhibits IL-6 action

57

Use:

Tocilizumab

Juvenile rheumatoid arthritis

58

Adverse effects:

Tocilizumab

increases risk for infection

59

MOA:

Rituximab

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

60

Use:

Rituximab

Chronic lymphoid leukemia
Non-hodgkin's lymphoma
Rheumatoid arthritis

61

Which monoclonal Immunosuppression Ab is not humanized?

Muromonab-CD3 (Orthoclone)

62

What are 3 Anti-TNF drugs?

Infliximab
Adalimumab
Etanercept

63

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

Adalimumab - humanized

Infliximab - mouse/human

Etanercept - fusion protein

64

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

TNF
IgG1

65

MOA:

Infliximab
Adalimumab
Etanercept

Bind circulating TNF --> NEUTRALIZES TNF activity

66

Use:

Infliximab
Adalimumab
Etanercept

Rheumatoid arthiritis
Psoriasis
Crohn's disease

67

Toxicity:

anti-TNF drugs

Inc risk for infection, lymphomas and other cancer

68

MOA:

Alefacept

binds CD2 on T cells

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

69

What type of fusion protein is Alefacept?

LFA-3 - IgG1

70

Use:

Alefacept

Treat psoriasis

71

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

T-cell Co-stimulation

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

72

MOA:

Abatacept/Belatacept

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

73

What type of fusion proteins are Abatacept/Belatacept?

CTLA-4 - IgG1

74

Use:

Abatacept?
Belatacept?

Toxicity?

Abatacept: treatment for juvenile idiopathic arthritis and Rheumatoid arthritis

Belatacept: prevent organ transplant rejection


- both inc risk for infection

75

What are immunostimulants used to treat? (2)

- Immunodeficiency
- bolster immunity against specific targets

76

Do immunostimulants act through cellular or humoral immunity?

Either one or BOTH

77

Magnitude of stimulation by immunostimulants can be highly ____

Variable

78

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

Nonspecific

contains all subclasses (IgG>IgM)

79

When is specific immune globulins used?

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

80

What does BCG stand for? (vaccine)

Bacillus Calmette-Guerin

81

What type of vaccine is BCG?

Live attenuated strain of Mycobacterium bovis

82

What is the active component of BCG?

Muramyl dipeptide

83

What does BCG stimulate?

NK cells and T cell activity

84

What is the primary use of BCG vaccine?

Treatment of bladder cancer

85

Toxicity:

BCG vaccine

severe hypersensitivity reaction

Shock

86

What are 3 synthetic agents that are used as immunostimulatory?

Levamisole
Isoprinosine
Thalidomide

87

Immunostimulatory function of Levamisole?

Inhibits T-suppressor cells

used for colon cancer

88

Immunostimulatory function of Isoprinosine?

Increase NK cell cytotoxicity and activity of T cells and monocytes

89

Immunostimulatory function of Thalidomide?

Decrease circulating TNF-a

90

What is Thalidomide used for?

Refractory arthritis
Erythema nodosum leprosum

91

What is a contraindication of thalidomide?

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

92

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

antiviral

Macs, T lymphocytes, NK cells

93

Use:

INF-a

Cancers
Hep B and C

94

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

both are immunostimulant

95

Toxicity

INF-a

Flu like symptoms
Pulmonary hypertension

96

MOA and Use:

IL-2

Activates cellular immunity

- metastatic melanoma, renal cell carcinoma, AIDS ptns

97

Toxicity:

IL-2

severe hypotension
Cardiovascular toxicity

Pulmonary Edema*** dose limiting

98

What does Granulocyte colony stimulating factors do?

Stimulate inc in numbers of granulocytes and monocytes

99

What produces glycoproteins (Granulocyte colony stimulating factors)?

Monocytes
Fibroblasts
Endothelial cells

100

What are granulocyte colony stimulating factors used for?

reduce neutropenia (esp due to chemotherapy)