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USLME Pharmacology > Immunosuppressants > Flashcards

Immunosuppressants Flashcards

1
Q

The recombinant cytokine Aldesleukin is an IL-2 used for which 2 clinical conditions?

A

RCC

metastatic melanoma

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2
Q

The recombinant cytokine Epoetin alfa is erythropoietin used in?

A

Anemias, especially in renal failure

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3
Q

The recombinant cytokine Filgrastrim is a G-CSF used to?

A

recover bone marrow

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4
Q

The recombinant cytokine Sargramostim is a GM-CSF used to?

A

recover bone marrow

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5
Q

The recombinant cytokine IFN-alpha used in?

A

Chronic hepatitis B and C
Kaposi sarcoma
malignant melanoma

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6
Q

The recombinant cytokine IFN-beta used in?

A

multiple sclerosis

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7
Q

The recombinant cytokine IFN-gamma used in?

A

Chronic granulomatous disease (NADPH oxidase deficiency -can’t take care of O2 produced and make HOCL) -more susceptible to catalase + organisms (2H2O2 –> 2H2O + O2)

“Cats Need PLACESS to hide”
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, Staphylococci, Serratia

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8
Q

The recombinant cytokines Romiplostim and eltrombopag used to treat?

A

thrombocytopenia

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9
Q

The recombinant cytokine Oprelvekin is a recombinant IL-11 used to treat?

A

thrombocytopenia b/c IL-11 can help in maturation of megakaryocytes

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10
Q

List the 3 recombinant cytokines to treat thrombocytopenia

A

-Romiplostim, eltrombopag, Oprelvekin (IL-11)

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11
Q

List the 2 recombinant cytokines used to recover bone marrow

A
  • Filgastrim (G-CSF)

- Sargramostim (GM-CSF)

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12
Q

Both cyclosporine and tacrolimus are immunosuppressants that inhibit calcinerin (impt in transcription of IL-2 for T cell activation), but they bind different proteins. State them

A

cyclosporine inhibits calcinerin by binding cyclophilin
tacrolimus inhibits calcineurin by binding FKBP

*Both block T-cell activation by blocking IL-2 transcription

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13
Q

List the 2 immunosuppressants that inhibit calcineurin. They share a very impt side effect, which is?

A

The 2 immunosuppressants: cyclosporine + tacrolimus are BOTH VERY NEPHROTOXIC

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14
Q

Cyclosporine is an immunosuppressant that inhibits calcineurin impt in transcription of IL-2 for activation of T-cell. No calcineurin = no tx of IL-2 = no activation of T cell. What are the clinical uses and side effects?

A

Clinical uses: tx rejection ppx, psorasis, rheumatoid arthritis
toxicity: nephrotoxicity, HTN, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism

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15
Q

Tacrolimus is an immunosuppressant that inhibits calcineurin (no calcineurin = no transcription of IL-2 = no activation of T cells). What are clinical uses and side effects?

A

Clinical uses: tx rejection ppx

toxicity: nephrotoxicity, increase risk of DIABETES, neurotoxicity

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16
Q

Sirolimus aka Rapamycin is an immunosuppressant that works how? What is it used in. toxicity?

A

Sirolimus (Rapamycin) is a mTOR inhibitor by binding FKBP. FKBP can bind mTOR to cause proliferation of genes. Sirolimus, as a mTOR inhibitor, blocks T cell activation and B cell differentiation by preventing response to IL-2. It is used in kidney tx rejection ppx.

Toxicity: bone marrow suppression, insulin resistance, hyperlipidemia.

17
Q

T/F: Sirolimus is syngergistic with Cyclosporine

A

Cyclosporine: calcineurin inhibitor prevents tx of IL-2 = no T cell activation
Sirolimus: mTOR inhibitor prevents T cell activation and B cell differentiation

True
*remember impt side effect of cyclosporine is nephrotoxicity; sirolimus is not nephrotoxic

18
Q

What are the 2 monoclonal antibodies used as immunosuppressant therapy to block IL-2R used in kidney tx rejection ppx? What are 3 side effects?

A
  • Basiliximab
  • Daclizumab

side effects: Edema, HTN, tremor

19
Q

Azathioprine is an anti-metabolite that is a prodrug to? It can be used as in immunosuppressant b/c? What are some side effects. Also, what drug is contraindicated?

A

Azathioprine is an antimetabolite that is a prodrug to 6-mercaptopurine that blocks nucleotide synthesis which will then inhibit lymphocyte proliferation.

Side effects are mainly bone marrow suppression. People on azathioprine or 6-mercaptopurine should not be on allopurinol b/c allopurinal is a xanthine oxidase inhibitor preventing uric acid build up but xanthine oxidase is the enzyme responsible for degrading azathioprine/6-MP.

20
Q

Glucocorticoids can be used as immunosuppressants as transplant rejection ppx because it? What are some side effects of long-term use?

A

glucocorticoids inhibit NF-kb, a nuclear transcription factor, that is impt in activating immune response genes. No NF-kb = suppression of both B and T cell function due to decrease tx of many cytokines.

side effects: hyperglycemia, osteoporosis, central obestiy, muscle breakdown, psychosis, acne, HTN, cataracts, avascular necrosis ***can cause iatrogenic cushing syndrome.

21
Q

Therapeutic antibodies: Alemtuzumab targets? used in?

A

Alemtuzumab targets CD52 used in chronic lymphocytic leukemia

CLL is the most common leukemia overall due to neoplastic proliferation of naive B cells that co-express CD5 and CD20; will see SMUDGE cells on blood smear)

22
Q

Therapeutic antibodies: Bevacizumab targets? used in? Similuar to which other therapeutic ab in that it also has the same target and uses?

A

Bevacizumab targets VEGF used in colorectal cancer, RCC.

Ranibizumab is also an antibody that blocks VEGF that can be used for neovascular age-related macular degeneration. In addition to being used in colorectal cancer and RCC, bevacizumab is also used for neovascular age-related macular degeneration.

23
Q

Therapeutic antibodies: Cetuximab targets? used in?

A

Cetuximab targets EGFR used in stage IV colorect cancer, head and neck cancer.

24
Q

Therapeutic antibodies: Rituximab targets? used in?

A

Rituximab targets CD20 and used in B-cell non-Hodgkin Lymphoma, CLL, rheumatoid arthritis, Immune thrombocytopenic purpura (ITP: autoimmune production of IgG against platelet antigens by plasma cells in the spleen –> MOST COMMON cause of thrombocytopenia in children and adults)

25
Q

Therapeutic antibodies: Trastuzumab targets? used in?

A

Trastuzumab is a monoclonal antibody that targets HER2/neu (a tyrosine kinase receptor) to treat breast cancer that overexpresses HER2. (kill cells via Ab-dependent cytotoxicity

26
Q

Therapeutic antibodies: Adalimumab, Infliximab target? used in?

A

Adalimuab and Infliximab target soluble TNF-alpha used in inflammatory bowel disease [chrohn’s or ulcerative], rheumatoid arthritis, anklosing spondylitis (bamboo spine, HLA-B27), psoriasis

27
Q

How is etanercept different from adalimumab and infliximab?

A

Adalimumab and Infliximab are monoclonal antibodies that target solube TNF-alpha. Etanercept is a DECOY TNF-alpha RECEPTOR and NOT a monoclonal antibody.

28
Q

Therapeutic antibodies: Eculizumab targets? used for?

A

Eclizumab targets complement protein C5 used in paroxymal nocturnal hemoglobinuria

PNH is anacquired defect in myeloid stem cells –> ABSENT glycosylphophatidylinosoital (GPI); GPI is impt in preventing cell from getting killed by complement b/c it anchors DAF & MIRL on RBC membranes that inhibit C3 convertase; At night, we breathe shallow (respiratory acidosis) that can activate complement –> intravascular hemolysis at night
***RBCS, WBCS, and PLTS are lysed (pg 49 in pathoma)

29
Q

Therapeutic antibodies: Natalizumab targets? used for? There’s a risk for what type of side effect?

A

Natalizumab targets alpha4-integrin used in multiple sclerosis and Chrohn’s.

Alpha4-integrin is impt in cell adhesion bringing WBCs into GI and CNS. If you inhibit alpha-4 integrin and prevent movement of WBCs and inflammatory cells thru CNS can be linked to progressive multifocal leukoencephalopathy in pts with JC virus (DNA virus -polyomavirus).

30
Q

Therapeutic antibodies: Abciximab targets? used for?

A

Abciximab targets platelet glycoproteins IIb/IIIa (impt in binding fibrinogen) used as antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention.

31
Q

Therapeutic antibodies: Denosumab targets? used for?

A

Denosumab targets RANKL (on osteoclast) used to treat osteoporosis by inhibiting osteoclast maturation by mimicking osteoprotegerin.

32
Q

Therapeutic antibodies: Digoxin immune Fab targets? used for?

A

Digoxin immune Fab targets digoxin and is used as an antidote to digoxin poisoning.

33
Q

Therapeutic antibodies: Omalizumab targets and used for?

A

Omalizumab targets IgE and is used in allergic asthma, prevents IgE binding to FceRI.

34
Q

Therapeutic antibodies: Palivizumab targets and used for?

A

Palivizumab targets RSV F protein used for RSV ppx in high-risk infants.

RSV = RNA virus in paramyxovirus family along with parainfluenzae, mumps and measles –> ssRNA, nonsegmented negative linear, helical.

USLME Pharmacology (15 decks)

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