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IHO-Week 4 > Drugs Targeting Immune System Function > Flashcards

Drugs Targeting Immune System Function Flashcards

1
Q

What are the categories of immunosuppressives?

A

glucocorticoids, antibiotics, antibodies and fusion proteins

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2
Q

What drugs are used to prevent rejection following BMT?

A

antibiotics (cyclosporin, tacrolimus), mTOR inhibitors

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3
Q

What are the glucocorticoids?

A

Dexamethasone, Prednisone

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4
Q

MOA for glucocorticoids

A

interfere with concentration, distribution and function of leukocytes; end result is a decrease in IL-2 and TNF-alpha

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5
Q

Tx uses of Glucocorticoids

A

given in pulse regimen with high doses for treatment of certain cancers

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6
Q

MOA for Cyclosporin and Tacrolimus

A

interfere with intracellular signaling that inhibits cell proliferation and cytokine production/release

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7
Q

What is the pathway for cyclosporin and tacrolimus to prevent tissue rejection?

A

bind to cytoplasmic proteins and inhibit calcineurin –> no NFAT induced transcription –> decrease IL-2 and IL-2R –> decrease cell proliferation

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8
Q

What are the antibodies and fusion proteins that inhibit the immune system?

A

alemtuzumab, denileukin difitux, ibritumomab, rituximab, tositumomab

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9
Q

What is the general MOA for the antibodies and fusion proteins?

A

selectively recruit the immune system to destroy cancer cells

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10
Q

What indications cause pt to be treated with abs or fusion proteins?

A

traditional chemo has failed or pt factors (age) prevent the use of cytotoxic drugs

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11
Q

What drugs target CD20?

A

Rituximab, Ibritumomab, Tositumomab

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12
Q

What drug targets CD52?

A

alemtuzumab

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13
Q

What is the MOA for denileukin difitux?

A

fusion protein that has diphtheria toxin coupled to IL-2 –> inhibits protein translation by inactivating EF2 –> kill cells expressing IL-2R

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14
Q

Tx uses for denileukin difitux

A

cutaneous T-cell lymphoma

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15
Q

Resistance to denileukin difitux

A

changes in target proteins preventing the binding of IL-2

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16
Q

Pharmacokinetics of denileukin difitux

A

IV admin

long-half life (3-6 months)

17
Q

Toxicity of antibodies

A

infusion rxn, hypersensitivity rxns (HAMA), infections (reactivation of TB)

18
Q

Toxicity of anti-CD abs

A

cardiac arrhythmia, tumor lysis syndrome

19
Q

What are specific toxicities seen with Alemtuzumab?

A

cough, tightness in chest

20
Q

What are specific toxicities seen with Ibritumomab and Tositumomab?

A

These abs are radiolabeled and can cause birth defects

21
Q

What cytokines are used as immune system stimulants?

A

IFN-alpha, IL-2, TNF-alpha

22
Q

What characteristics do the cytokines share?

A

short half lives, not cytotoxic on their own, recruit immune cells to do the killing, can have serious/fatal side effects

23
Q

What are uses for IL-2?

A

either used alone to induce T cell response to tumor cells or to induce LAK/CIK cells

24
Q

What are the specific toxicities for IL-2?

A 
cytokine storm (inflammation, vascular leakage, fever, chills, etc.), hand-foot syndrome,
fatal hypotension
25
Q

What is the MOA for IFN-alpha tumor cell killing?

A
  • decreases the production of Fibroblast Growth Factor (FGF) –> inhibits cell division in normal and tumor cells
  • increases MHC I expression on tumor cells (CD8+ do killing)
26
Q

What are the specific toxicities of IFN-alpha?

A

flu-like sx, hypotension, BM suppression, depression

27
Q

What is MOA for TNF-alpha tumor cell killing?

A

similar to IL-1 –> cause fibroblast proliferation, cytokine release, B cell activation
–> decrease proliferation of tumor cells specifically

28
Q

What is specific about TNF-alpha administration?

A

must be done intra-arterially because of the short half life (minutes) and bad AE

29
Q

What are the toxicities of TNF-alpha?

A

malaise and flu-like sx that can cause cause hemorrhagic necrosis

30
Q

What are the hematopoietic agents?

A

EPO, Filgrastim, IL-11, Romiplostim, Sargramostim

31
Q

What is the purpose of administering hematopoietic agents with antineoplastics?

A

BM suppression is dose-limiting complication so these drugs work to stimulate progenitor cells

32
Q

What are the cell populations stimulated by the different hematopoietic agents?

A

EPO –> RBC
Filgrastim –> neutrophils
Sagramostim –> eosinophils, basophils, monocytes
IL-11 –> platelets

IHO-Week 4 (6 decks)

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