Immunosuppresive Agents : )

Question 1

What are 3 type of drugs used for prevention of transplant rejection

Answer 1

1. Glucocorticoids
2. immunophilin ligands
3. mycophenolate

Question 2

what are the 3 types of immunophilin ligands

Answer 2

1. cyclosporine
2. tacrolimus
3. sirolimus

Question 3

explain the MOA of cyclosporine

Answer 3

cyclosporine is a peptide that binds intracellular cyclophilin to form a complex that inhibits the phosphatase cacineurin

Question 4

what is cacineurin/what is it needed for

Answer 4

Ca2+ calmodulin activated enzyme. Needed for the activation of NF-AT(transcription factor)

Question 5

what is NF-AT used for?

Answer 5

required for the expression of IL-2

Question 6

why is IL-2 needed?

Answer 6

IL-2 is essential for T-cell maturation which are involved in acute transplant rejection

Question 7

explain the MOA of tacrolimus

Answer 7

• binds to immunophilin FK-binding protein (FKBP)
• this inhibits calcineurin
• this inhibits expression of IL-2

Question 8

what is the MOA of siromilus

Answer 8

• binds immunophilins and acts similar tocromilus and cyclosporine
• also inhibits B cells

Question 9

what is a derivative of sirolimus and what is it used for

Answer 9

everolimus: used for cardiac transplantation

Question 10

what is the MOA of mycophenolate mofetil (MMF, CellCept)

Answer 10

inhibits de novo purine synthesis (guanine nucleotide)

Question 11

CU of thalidomide

Answer 11

treatment of multiple myeloma

Question 12

MOA of thalidomide

Answer 12

inhibits angiogenesis and TNF-α. —> has inflammatory activity

Question 13

S/Es of thalidomide

Answer 13

TERATOGENIC

• Amelia (absence of arm)
• phocomelia (short stumps for limbs)

Question 14

what type of agent is azathioprine

Answer 14

cytotoxic

Question 15

mercaptopurine’s prodrug is what?

Answer 15

azathioprine

Question 16

cyclophosphamide is what type of drug

Answer 16

cytotoxic agent

Question 17

describe leflunomide (CU, prodrug of…, )

Answer 17

cytotoxic agent : prodrug of pyrimidine biosynthetic inhibitor
-inhibits mitochondrial dihydroorotate dehydrogenase
CU: rheumatoid arthritis

Question 18

what type of drug is hyroxychloroquine and how does it work

Answer 18

cytotoxic agent : interferes with the antigen presentation on major histocompatability complex (MHC)

Question 19

what is hyroxychloroquine used to treat?

Answer 19

• malaria
• systemic rheumatic disorders (RA,lupus, jorgen’s syndrome, porphyria)
• post Lyme arthritis

Question 20

what does hyroxychloroquine do in inflammatory conditions?

Answer 20

blocks toll-like receptors on plasmacytoid dendritic cells (PDCs) hehe

Question 21

What is the role of toll like receptors -9?

Answer 21

TLR-9 recognize DNA immune complexes leading to the production of interferon
—>causes dendritic cells to mature and present antigen to T cells

Question 22

what happens when hyroxychloroquine decreases TLR signaling?

Answer 22

reduces the activation of dendritic cells and the inflammatory process

Question 23

what kind of inhibitor is pentostatin (nipent)

Answer 23

adenosine deaminase inhibitor

Question 24

what is pentostatin used for

Answer 24

• lymphoid malignancies
• hairy cell leukemia
• steroid refractory acute and chronic graft-versus-host disease
• chronic lymphocytic leukemia in relapsed patients

Question 25

MOA of pentostatin

Answer 25

purine analog that mimics adenosine, inhibiting adenosine deaminase interfering with DNA metabolism

Question 26

heterologous antilymphocyte globulin (HAG) and antithymocyte globulin (ATG) is used for what?

Answer 26

transplant rejection. they are monoclonal or polyclonal antibodies (idk which...eep) : (

Question 27

describe Muromonab -CD3 and what it is used for

Answer 27

monoclonal antibody against CD3 receptor. Prevents transplant rejection

Question 28

describe Immunoglobulin IV and what it is used for

Answer 28

fractionated gamma globulin from pooled serum. used for -passive immunization of certain immunodeficiencies - kawasaki disease (inflam of blood vessels) - ideopathic immunothrombocytopenic purpura

Question 29

what is Rh(D) Immune Globulin and what is it used for

Answer 29

anti Rh antibodies given to Rh (-) mothers within 24-72 hrs of delivery to prevent sensitization

Question 30

what may happen to the newborn if the mother is sensitized

Answer 30

hemolytic disease of the newborn (HDN) / erythroblastosis fetalis may occur

Question 31

alemtuzumab (campath)

Answer 31

humanized anti CD52 MAB used for B cell chronic lymphocytic leukemia

Question 32

Bevacizumab (Avastin)

Answer 32

Humanized anti VEGF MAB is antiangiogenic used for colorectal carcinomas in combination therapy.

Question 33

Cetuximab (Erbitux)

Answer 33

humanized anti EGFR MAB

Question 34

Gemtuzumab (Mylotarg)

Answer 34

humanized anti CD33 MAB used for acute myelogenous leukemia (AML)

Question 35

Gemtuzumab-ozogomycin (mylotarg)

Answer 35

combination is available for targeted delivery. Ozogomycin causes strand scission in DNA

Question 36

Rituximab (Rituxan)

Answer 36

Humanized anti CD20 MAB used for B cell non Hodgkin's lymphoma

Question 37

Trastuzumab (Herceptin)

Answer 37

humanized anti Her2 - Neu MAB used for Her2-New positive metastatic breast cancers

Question 38

what radioactive isotopes are targeted and delivered by MABs

Answer 38

99Tc, 90Y, 111In, 131I.

Question 39

how do MABS as anti-inflammatory agents work

Answer 39

they are anti-tumor necrosis factor (TNF) - alpha antibodies. TNF-alpha is a proinflammatory cytokine

Question 40

what is adalimumab (humira) and what is it used for

Answer 40

``` humanized monoclonal antibody. -rheumatoid arthritis - psoriatic arthritis(PsA) -plaque psoriasis ideopathic juvenile ankylosing spondylitis -crohns disease ```

Question 41

what is etanercept (enbrel)

Answer 41

recombinant fusion protein containing TNF-alpha receptor ligand binding domain and human Fcgamma portion

Question 42

what is etanercept used to treat

Answer 42

- rheumatoid arthritis - psoriasis, - ankylosing spondylitis, - psoriatic arthritis - - juvenile rheumatoid arthritis.

Question 43

what does infliximab (remicade) treat

Answer 43

- Crohn's/ peds chrohn's disease - rheumatoid arthritis - psoriatic arthritis - plaque psoriasis, - ankylosing spondylitis - Ulcerative colitis,

Question 44

what is infliximab and what is it composed of

Answer 44

chimeric IgG1κ monoclonal antibody. -It is composed of human constant and murine variable regions. Infliximab binds specifically to human TNFα with an association constant of 1010 M-1.

Question 45

what is Ustekinumab (Stelara) and what is used to treat

Answer 45

monoclonal antibody against IL -12 and IL-23. Treats plaque psoriasis.