Final Exam

Question 1

calcineurin inhibitors MOA

Answer 1

inhibition of calcineurin phosphatase enzyme within T-cell -> inhibits T-cell activiation

Question 2

cyclosporine target trough

Answer 2

100-400 ng/ml

Question 3

cyclosporine metabolism

Answer 3

cyp3a4 and p-glycoprotein

Question 4

cyclosporine adverse effects

Answer 4

1. hirsutism
2. gingival hyperplasia
3. HTN
4. Hypertriglyceridemia
5. Hypercholesterolemia

Question 5

which one has a more variable t1/2: cyclosporine or tacrolimus?

Answer 5

cyclosporine

Question 6

tacrolimus target trough

Answer 6

5-15 ng/ml

Question 7

tacrolimus metabolism

Answer 7

cyp3a4

Question 8

tacrolimus adverse effects

Answer 8

1. alopeica
2. hyperglycemia -> PTDM
3. neurotoxicity (insomnia, headache, dizziness)

Question 9

tacrolimus brand names

Answer 9

1. Prograf
2. Astagraf XL
3. Envarsus XR

Question 10

cyclosporine brand names

Answer 10

1. sandimmune (non-modified)
2. Neoral (modified)
3. Gengraf (modified)

Question 11

cyp450 inducers (decrease CSA/FK conc)

Answer 11

1. phenytoin
2. carbamazepine
3. phenobarbital
4. rifampin

Question 12

cyp450 inhibitors (increase CSA/FK conc)

Answer 12

1. erithromycin, clarithromycin
2. azoles
3. diltiazem, verapamil
4. ritonavir
5. grapefruit juice

Question 13

Which one alters the PK of CNIs: renal or liver dysfunction?

Answer 13

liver dysfunction

Question 14

Azathioprine (AZA) MOA

Answer 14

AZA converted to 6-MP which is incorporated into nucleic acids, so RNA and DNA synthesis is inhibited (and therefore immune cell proliferation)

Question 15

Azathioprine brand name

Answer 15

Imuran

Question 16

Does AZA require TDM?

Answer 16

No

Question 17

AZA drug interactions

Answer 17

allopurinol, febuxostat

Question 18

AZA adverse effects

Answer 18

1. GI: N/V/D, pain
2. Bone marrow suppression -> anemia, leukopenia, neutropenia, thrombocytopenia

Question 19

Which antimetabolite is most commonly used in combination with CNIs?

Answer 19

Mycophenolate (usually with tacrolimus)

Question 20

Mycophenolate MOA

Answer 20

Inhibits de novo synthesis pathway of purine synthesis -> limits progression of activated T and B cells

Question 21

Mycophenonlate brand names

Answer 21

1. Mycophenolate mofetil: CellCept (IR)
2. Mycophenolate sodium: Myfortic (DR)

Question 22

Can mycophenolate be used in pregnancy?

Answer 22

NO - category D/teratogenic

Question 23

Mycophenolate REMS program

Answer 23

Formal consent for women of childbearing potential - 2 forms of birth control required

Question 24

Mycophenolate drug interactions

Answer 24

Other myelosuppressive drugs (i.e. valganciclovir, sirolimus) leads to additive myelosuppression

Question 25

Calcineurin inhibitors

Answer 25

Tacrolimus (FK) Cyclosporine (CSA)

Question 26

Antimetabolites

Answer 26

Azathioprine (AZA) Mycophenolic acid (MPA)

Question 27

mTOR inhibitors

Answer 27

Sirolimus (SRL) Everolimus (EVR)

Question 28

Sirolimus brand name

Answer 28

Rapamune

Question 29

Everolimus brand name

Answer 29

Zortress

Question 30

Sirolimus indication

Answer 30

kidney transplant rejection prophylaxis

Question 31

Everolimus indication

Answer 31

kidney and liver transplant rejection prophylaxis

Question 32

Sirolimus and Everolimus adverse effects

Answer 32

1. Edema 2. Hyperlipidemia 3. Hypertriglyceridemia 4. Impaired wound healing 5. Mouth ulcers 6. Proteinuria

Question 33

Why are you unable to use mTOR inhibitors immediately post-op?

Answer 33

Because of impaired wound healing (and risk of thrombosis)

Question 34

Which immunosuppressive drugs may cause hypertriglyceridemia?

Answer 34

Cylcosporine Sirolimus Everolimus

Question 35

T-cell co-stimulation blocker

Answer 35

Belatacept (Nulojix)

Question 36

Belatacept is contraindicated in what?

Answer 36

1. Liver transplant 2. EBV seronegative patients

Question 37

How is belatacept administered?

Answer 37

Every 4 weeks IV at an infusion clinic

Question 38

Belatacept place in therapy

Answer 38

Replacement of adjunct to CNIs

Question 39

Drug of choice - PJP

Answer 39

SMX-TMP (atovaquone if sulfa allergy)

Question 40

Drug of choice - CMV

Answer 40

ganciclovir (IV) or valganciclovir (PO)

Question 41

Drug of choice - aspergillus

Answer 41

Posoconazole

Question 42

Typical immunosuppressive 3-drug regimen

Answer 42

Tacrolimus + Mycophenolate +/- prednisone