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Block 5 Pharmacology > Immunomodulators > Flashcards

Immunomodulators Flashcards

(68 cards)

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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
What is the mechonism of action of azathioprine
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?
26
How is azathioprine administered
oral | parenteral
27
How is azathioprine eliminated
Renal
28
What are 2 clinical uses of azathioprine
Prevents organ transplant rejection | Rheumatoid arthritis
29
What are 2 adverse effects of azathioprine
Bone marrow suppression | Hepatotoxicity
30
What is the mechanism of action of prednisone
Inhibits proliferation of lymphoid cells | inhibits production of inflammatory mediators like interleukins, prostaglandins, leukotrienes and histamine
31
How is prednisone administered
Oral
32
How is prednisone metabolized
ACTIVATED TO PREDNISOLONE by the liver
33
How is prednisone eliminated
Renal
34
What are 4 clinical uses for prednisone
Non hodgkins lymphoma (CHOP-R) Transplant rejection prevention Graft vs host prevention Autoimmune disease
35
What are the short term adverse effects of prednisone
well tolerated
36
What are teh long term adverse effects of prednisone
muscle wasting cushing syndrome inhibits osteoblast protein production
37
What are 2 cytokines with anticancer activity
aldesleukin | interferon alpha
38
how do cytokines in general work
produced mainly by white blood cells and regulate the growth inflammation and other immune responses
39
What is the mechanism of action of aldesleukin
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
how is aldesleukin administered
parenteral
41
how is aldesleukin eliminated
renal
42
What are the 2 clinical uses of aldesleukin
renal cell carcinoma | metastatic melanoma
43
what are the low dose adverse effects of aldesleukin
well tolerated
44
what are 3 high dose adverse effects of aldesleukin
capillary leak syndrome (hypotension) thrombocytopenia Neutropenia
45
What is the mechanism of action of interferon alpha
Is a cytokine which increases activity of immune cells which then inhibit the growth of tumor cells
46
How is interferon alpha administered
parenteral
47
How is interferon alpha eliminated
Renal
48
What are the 2 clinical uses of interferon alpha
melanoma | kaposi sarcoma
49
what are 2 adverse effects of interferon alpha
myleosuppression | flulike illness
50
What are 3 hematopoietic growth factors
G-CSF (Filgrastim) GM-CSF (Sargramostim) EPO
51
What is the mechanism of action of EPO
binds to epo receptors on red cell progenitors to stimulate proliferation and differentiation INDUCES release of ERYTHROCYTES from bone marrow
52
How is EPO administered
Parenteral
53
What are 3 clinical uses of EPO
Anemia of chronic renal failure (EPO synthed in kidney ) Cancer intermittent therapy HIV
54
What are 3 adverse effects of EPO
Hypertension thrombotic complications allergic reactions
55
What is the mechanism of action of Filgrastim
Granulocyte colony stimulating factor (G-CSF) | binds to receptors on myeloid progenitor cells to stimulate differentiation and proliferation of granulocytes
56
What is the effect of Filgrastim
increases diff/ prolif of granulocytes to: shorten duration of neutropenia dec infection rates dec days of hospitalization
57
What is the clinical use of filgrastim
Restore bone marrow cells following chemo and bone marrow transplant
58
What is the adverse effect of filgrastim
mild to moderate bone pain
59
What is the mechanism of action of Sargramostim
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
What is the effect of sargramostim
increases diff/proliff of granulocytes/macrophages to : Shorten duration of bone marrow suppression dec infection rates dec days of hospitalization
61
What is the clinical use of sargramostim
Restore bone marrow cells following chemo and bone marrow transplant
62
What are 4 adverse effects of sargramostim
fever myalgia malaise capillary leak syndrome
63
What is the mechanism of action of plerixafor
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
What is the clinical use of plerixafor
muliple myeloma | non hodgkins lymphoma
65
WHat is the use of gardasil
chemoprevention vaccine prevent cervical cancer/genetial warts from HPV 6,11,16,18 Target females and males 9-26
66
What is the MOA of Gardasil
L1 capsid protein (of HPV6 and 11 for warts) (of 16and 18 for cervical cancer) Not an attenuated virus
67
how is gardasil administered
3 im shots | 0 2 and 6 months
68
what are 3 adverse effects associated with gardasil
fever pain at injection site hypersensitivity reactions

Block 5 Pharmacology (8 decks)

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