Drugs used in Organ Transplantation

Question 1

Glucocorticoids MOA is…

Answer 1

suppress distribution and reactivity of lymphoid and myloid cells

catabolic actions at GRE

Question 2

The main use of glucocorticoids is…

Answer 2

acute use when needed or early on, or in emergencies

Question 3

Antithymocyte Globulin (ATG) and Antilymphocyte Globulin (ALG)

Answer 3

MOA- polyclonal suppression of thymocytes (T) or lymphocytes (T&B, NK cells)

Question 4

The administration of what drugs allows early temporary withdrawal of all other drugs?

Answer 4

ATG and ALG

Question 5

Muromonab-CD3 (OKT-3)

Answer 5

Is a MAB against the T- cell receptor

Question 6

Alemtuzumab

Answer 6

human MAB against Cd52 on lymphocytes, monocytes, macrophages, NK

Prolonged T and B cell depletion

Question 7

What drug is used in CLL?

Answer 7

Alemtuzumab

Question 8

Daclizumab and Basiliximab

Answer 8

humanized and chimeric MABs against IL-2 receptor on T-cell

Question 9

Daclizumab and Basiliximab are used more for…

Answer 9

acute renal rejections

Question 10

Abatacept and Belatacept

Answer 10

Fusion of Fc of IgG1 and CTLA-4 –> binds to CD80/CD86 –> suppression of T-cell activation

Question 11

Thalidomide

Answer 11

• stimulates and changes specificity of T-cells
• suppresses B-cells
• stimulates T-cells but in an immunomodulatory fashion

Question 12

What are two calcineurin inhibitors?

Answer 12

Cyclosporine (CSA)

Tacrolimus (FK-506)

Question 13

Calcineurin inhibitors…

Answer 13

block signal transduction activating t-cells

Question 14

What does Cyclosporine bind to?

Answer 14

Cyclophilin

Question 15

What does tacrolimus bind to?

Answer 15

FK-506BP12

Question 16

What are the two antiproliferative agents?

Answer 16

Sirolimus (Rapamycin)

Everolimus

Question 17

Sirolimus and Everolimus…

Answer 17

inhibit mTOR kinase activity –> prevents CDK2 phosphorylation –> blocks cell cycle progression in T-cells

Question 18

Sirolimus and Everolimus have drug-drug interactions at what enzyme?

Answer 18

CYP450s

Question 19

What antimetabolites are used for organ transplantation?

Answer 19

Mycophenolate Mofetil

Azathioprine

Question 20

MMF

Answer 20

is a prodrug

Question 21

What is MMF converted to in order to become active?

Answer 21

mycophenolic acid

Question 22

What is the MOA of MMF?

Answer 22

inhibits T and B cell inosine monophosphate dehydrogenase in purine pathway for GMP synthesis

Question 23

What is the active form of azathioprine?

Answer 23

6-MP

Question 24

What is the MOA of 6-MP or AZA?

Answer 24

inhibits ATP and GTP synthesis

Question 25

What recurrent symptom is seen with cyclosporine use?

Answer 25

gum hyperplasia in heart transplant patients

Question 26

Lip hypertrophy is seen with cyclosporine (CsA) and is reversed with…

Answer 26

Tacrolimus (FK506 inhibitor)

Question 27

Tacrolimus binds FK506 first and then binds and inhibits…

Answer 27

PP2B- phosphatase activity of calcineurin

Question 28

What drug is associated with diabetogenesis when combined with glucocorticoids?

Answer 28

Tacrolimus

Question 29

What is mTOR?

Answer 29

a serine/threonine protein kinase inhibited by sirolimus

Question 30

What drugs prevent de novo purine synthesis which is important for B- and T- cells?

Answer 30

MMF

Question 31

When combined with AZA, what drug needs to have a dose reduction due to inhibition of xanthine oxidase?

Answer 31

Allopurinol- used for hyperuricemia and crystalluria associated with cell death/gout therapy