Solid Organ Transplant

Question 1

Immunogenicity of various organs

Answer 1

Least to most:
Liver
Kidney 
Pancreas
Heart
Lungs
GI

Question 2

Induction therapy three main drugs

Answer 2

Basiliximab
Antithymocyte globulin
Alemtuzumab

Question 3

Basliximab (Simulect) MOA

Answer 3

Blocks T-cell proliferation via IL-2 receptor antagonism (anti-CD25 antibody)
Lowest immunologic risk pts. and short MOA

Question 4

Antithymocyte globulin (Thymoglobulin) MOA

Answer 4

Binds to T-cell surface antigens leading to the depletion of T-cells
Used in moderate immunologic patients

Question 5

Alemtuzumab (Campath)

Answer 5

Binds to CD52 on Tcells, Bcells, NK cells, and macrophages causing complement activation and antibody dependent cellular toxicity
1+ years of recovery, very strong and long lasting

Question 6

Maintenance therapy medications

Answer 6

Corticosteroids
Calcineurin inhibitors
Antimetabolites
mTOR inhibitors

Question 7

Corticosteroids MOA

Answer 7

Inhibition of cytokine gene expression
Modification of lymphocyte distribution and fxn
Anti-inflammatory

Question 8

Prednisone maintenance dosing

Answer 8

5-10 mg/day

Question 9

Tacrolimus MOA

Answer 9

Inhibits T-cell activity through inhibition of IL-2 production

Question 10

Tacrolimus metabolism

Answer 10

CYP3A4 (drug interxns) and p-glycoprotein (higher absorption with diarrhea)

Question 11

Tacrolimus dosing

Answer 11

Immediate release: 0.05-.1 mg/kg/day divided doses(general flat dose of 2mg bid)
Extended release: 0.1/0.2 mg/kg/day

Question 12

Tacrolimus therapeutic range

Answer 12

5-15 ng/mL

Question 13

Cyclosporine MOA

Answer 13

Inhibits T-cell proliferation through inhibition of IL-2 production

Question 14

Cyclosporine dosing

Answer 14

10-15 mg/kg/day in divided doses

Question 15

Cyclosporine therapeutic range

Answer 15

50-200 ng/mL

Question 16

Mycophenolate MOA

Answer 16

Inhibition of inosine monophosphate dehydrogenase (IMPDH) which inhibits de novo guanosine nucleotide synthesis
Prevents T and B lymphocytes proliferation

Question 17

Mycophenolate dosing

Answer 17

250-1000 mg bid (MMF)
180-720 mg bid (Myfortic)

Conversion: 1000 mg Cellcept = 720 mg Myfortic

Question 18

Mycophenolate precautions

Answer 18

Teratogenic, no pregnancy within one year

Question 19

Azathioprine MOA and uses

Answer 19

Prodrug of 6-MP which antagonizes purine metabolism and prevents T and B cell proliferation
Uses: Intolerance to mycophenolate and women that want to become pregnant

Question 20

Azathioprine dosing

Answer 20

3-5 mg/kg/day, then decrease to 1-3 mg/kg/day

Question 21

Sirolimus MOA

Answer 21

Binds to FKBP-12 which inhibits mTOR leading to supression of cytokine T-cell proliferation

Question 22

Sirolimus uses

Answer 22

May be used to replace mycophenolate or calcinerium inhibitor

Question 23

Sirolimus dosing

Answer 23

1-5 mg/day to achieve target trough levels (same as tacrolimus)

Question 24

Everolimus uses

Answer 24

Renal and heart transplant rejection prophylaxis.

Very expensive and just as effective as sirolimus

Question 25

Belatacept MOA

Answer 25

Binds to CD80 and CD86 receptors on APCs and blocking the CD28-mediated co-stimulation of T-cells

Question 26

Belatacept dosing

Answer 26

Initial: 10 mg/kg IV on select weeks
Maintenance: 5 mg/kg q 4 weeks
NO nephrotoxicity