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Block 5 Pharmacology > Immunomodulators > Flashcards

Immunomodulators Flashcards

1
Q

What are immunomodulators for and what are 4 agents considered these

A

modulate activity of immune cells

  • Immunosuppressants
  • cytokines
  • Hemnatopoietic Growth Factors
  • Vaccines
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2
Q

What are immunosuppressants for and what are 3 agents considered these

A

Used to prevent organ rejection and graft vs host and used to treat autoimmune disease

  • Immunophilin Ligands
  • DNA synthesis inhibitors
  • Glucocorticoids
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3
Q

What are 2 commonly utilized immunophillin ligands

A

Sicrolimus

Cyclosporine

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4
Q

What are 2 common DNA synthesis Inhibitors

A

Mycophenolate Mofetil

Azathioprine

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5
Q

How are drugs utilized after transplant

A

Various combinations and drugs of immunomodulators

also antimicrobials given prophylactically and therapeutically for infections

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6
Q

What is the mechanism of action of Cyclosporine

A

Cyclosporine enters the cell and binds to Cylclophilin and the complex inhibits calcineurin activity
This prevents IL-2 synthesis and blocks T cell proliferation

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7
Q

How is cyclosporine administered

A

Parenteral
oral
topical

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8
Q

How is cyclosporine metabolized

A

Hepatic

P450 Cyp 3A4

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9
Q

What are the 4 clinical uses of Cyclosporine

A

Prevents Trasnplant rejection
Prevents Graft vs Host Disease
Severe dry ey syndrome
autoimmune diseases

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10
Q

What are 2 adverse effects of cyclosporine

A

nephrotoxicity

Diabetogenic (+glucocorticoids)

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11
Q

What is the Mechanism of action of Sirolimus

A

Immunophilin ligand
Binds FKBP12 to inhibit mTOR
This inhibits the progression of cell cycle progression by inhibiting protein synthesis
Thus it inhibits t and b cell proliferations

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12
Q

How is Sirolimus administered

A

Oral

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13
Q

How is Siroliumus Metabolized

A

P450

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14
Q

What are the 2 clinical uses of Sirolimus

A

Transplat rejection prevention

Graft vs host disease prevention

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15
Q

What are 2 adverse effects of sirolimus

A

myelosuppression

hyperlipidemia

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16
Q

What is the mechanism of action of Mycophenolate mofetil

A

DNA synthesis Inhibitor
ACTIVE VERSION IS mycophenolic acid (MPA)
Hydrolyzed to active MPA in the liver and non competitively inhyibits inosine monophosphate dehydrogenase (IMPDH)

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17
Q

How does mycophenolate mofetil get its selectivity towards t and b lymphocytes

A

inhibits impdh which is esssential for the de novo purine pathway
de nobo pathway is mostly used in t and b lymphocytes, other cells can use the salvage pathway

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18
Q

How is mycophenolate mofetil administered

A

oral

parenteral

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19
Q

How is mycophenolate mofetil administered

A

decreased absorption with antacids / aluminum and magnesium containing food

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20
Q

How is mycophenolate mofetil eliminated

A

Renally

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21
Q

How is mycophenolate mofetil metabolized

A

MM (prodrug) in liver –> MPA (active) –> MPAG (glucuronidated inactive)

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22
Q

What are the 2 common clinicical uses of mycophenolate mofetil

A

prevents transplant rejection

prevents graft vs host disease

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23
Q

What is an adverse effect seen with myophenolate mofetil

A

GI irritation N/D/V

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24
Q

What drug interacts with mycophenolate mofetil and how

A

Tacrolimus
Decreases elimination by blocking the conversion of active MPA to inactive MPAG
this causes fatal infections and increases GI toxicity

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25
Q

What is the mechonism of action of azathioprine

A

converted to 6 mercaptopurine (6-MP) through non enzymatic removal of the nitroimidazole group and inhibits DNA synthesis in t cells
JUST LIKE 6MP and 6TG only can be given orally?

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26
Q

How is azathioprine administered

A

oral

parenteral

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27
Q

How is azathioprine eliminated

A

Renal

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28
Q

What are 2 clinical uses of azathioprine

A

Prevents organ transplant rejection

Rheumatoid arthritis

29
Q

What are 2 adverse effects of azathioprine

A

Bone marrow suppression

Hepatotoxicity

30
Q

What is the mechanism of action of prednisone

A

Inhibits proliferation of lymphoid cells

inhibits production of inflammatory mediators like interleukins, prostaglandins, leukotrienes and histamine

31
Q

How is prednisone administered

A

Oral

32
Q

How is prednisone metabolized

A

ACTIVATED TO PREDNISOLONE by the liver

33
Q

How is prednisone eliminated

A

Renal

34
Q

What are 4 clinical uses for prednisone

A

Non hodgkins lymphoma (CHOP-R)
Transplant rejection prevention
Graft vs host prevention
Autoimmune disease

35
Q

What are the short term adverse effects of prednisone

A

well tolerated

36
Q

What are teh long term adverse effects of prednisone

A

muscle wasting
cushing syndrome
inhibits osteoblast protein production

37
Q

What are 2 cytokines with anticancer activity

A

aldesleukin

interferon alpha

38
Q

how do cytokines in general work

A

produced mainly by white blood cells and regulate the growth inflammation and other immune responses

39
Q

What is the mechanism of action of aldesleukin

A

is a recombinant version of the t cell growth factor IL2

so it activates and induces proliferation of t cells, also activates and recurits t and b cells

40
Q

how is aldesleukin administered

A

parenteral

41
Q

how is aldesleukin eliminated

A

renal

42
Q

What are the 2 clinical uses of aldesleukin

A

renal cell carcinoma

metastatic melanoma

43
Q

what are the low dose adverse effects of aldesleukin

A

well tolerated

44
Q

what are 3 high dose adverse effects of aldesleukin

A

capillary leak syndrome (hypotension)
thrombocytopenia
Neutropenia

45
Q

What is the mechanism of action of interferon alpha

A

Is a cytokine which increases activity of immune cells which then inhibit the growth of tumor cells

46
Q

How is interferon alpha administered

A

parenteral

47
Q

How is interferon alpha eliminated

A

Renal

48
Q

What are the 2 clinical uses of interferon alpha

A

melanoma

kaposi sarcoma

49
Q

what are 2 adverse effects of interferon alpha

A

myleosuppression

flulike illness

50
Q

What are 3 hematopoietic growth factors

A

G-CSF (Filgrastim)
GM-CSF (Sargramostim)
EPO

51
Q

What is the mechanism of action of EPO

A

binds to epo receptors on red cell progenitors to stimulate proliferation and differentiation
INDUCES release of ERYTHROCYTES from bone marrow

52
Q

How is EPO administered

A

Parenteral

53
Q

What are 3 clinical uses of EPO

A

Anemia of chronic renal failure (EPO synthed in kidney )
Cancer intermittent therapy
HIV

54
Q

What are 3 adverse effects of EPO

A

Hypertension
thrombotic complications
allergic reactions

55
Q

What is the mechanism of action of Filgrastim

A

Granulocyte colony stimulating factor (G-CSF)

binds to receptors on myeloid progenitor cells to stimulate differentiation and proliferation of granulocytes

56
Q

What is the effect of Filgrastim

A

increases diff/ prolif of granulocytes to:
shorten duration of neutropenia
dec infection rates
dec days of hospitalization

57
Q

What is the clinical use of filgrastim

A

Restore bone marrow cells following chemo and bone marrow transplant

58
Q

What is the adverse effect of filgrastim

A

mild to moderate bone pain

59
Q

What is the mechanism of action of Sargramostim

A

Granulocyte-Macrophage colony stimulating factor (GM-CSF)
binds to receptors on myeloid progenitor cells to stimulate differentiation and proliferation of granulocytes and monocytes/macrophages

60
Q

What is the effect of sargramostim

A

increases diff/proliff of granulocytes/macrophages to :
Shorten duration of bone marrow suppression
dec infection rates
dec days of hospitalization

61
Q

What is the clinical use of sargramostim

A

Restore bone marrow cells following chemo and bone marrow transplant

62
Q

What are 4 adverse effects of sargramostim

A

fever
myalgia
malaise
capillary leak syndrome

63
Q

What is the mechanism of action of plerixafor

A

Binds to CXCR4 on HSC to prevent binding to SDF1a on marrow thus freeing it
mobilizes hematopoietic stem cells which is what all blood cells derive from
combine with GCSF to mobilize hsc to the peripheral blood for subsequent transplant
More effective than bone marrow aspirate and gcsf alone

64
Q

What is the clinical use of plerixafor

A

muliple myeloma

non hodgkins lymphoma

65
Q

WHat is the use of gardasil

A

chemoprevention vaccine
prevent cervical cancer/genetial warts from HPV 6,11,16,18
Target females and males 9-26

66
Q

What is the MOA of Gardasil

A

L1 capsid protein (of HPV6 and 11 for warts) (of 16and 18 for cervical cancer)
Not an attenuated virus

67
Q

how is gardasil administered

A

3 im shots

0 2 and 6 months

68
Q

what are 3 adverse effects associated with gardasil

A

fever
pain at injection site
hypersensitivity reactions

Block 5 Pharmacology (8 decks)

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