transplant drugs

Question 1

What are the two kinds of drugs you give during the induction phase?

Answer 1

ATG and anti IL-2R Antibodies

Question 2

What are the lymphocyte depleting agents (anti CD3 Abs)?

Answer 2

ATG (antithymocyte globulin) (polyclonal) and OKT3 (monoclonal) (taken off market)

Question 3

MOA of ATG?

Answer 3

T cell depletion via blockade of surface receptors; ATG is preferred in pts who are high risk

Question 4

Side effects of ATG?

Answer 4

cytokine release syndrome (pulmonary edema, n/v, fever, chills), leukopenia, thrombocytopenia

Question 5

What are the anti-CD25 Antibodies (anti IL-2R Abs)?

Answer 5

Basiliximab, Daclizumab

Question 6

MOA of Basiliximab/Daclizumab?

Answer 6

IL-2 receptor (CD25) blockade; given in low risk pts

Question 7

Side effects of Basiliximab/Daclizumab?

Answer 7

hypersensitivity reactions

Question 8

What is the co-stimulation blocker?

Answer 8

Belatacept

Question 9

MOA of Belatacept?

Answer 9

blocks co-stimulation by binding to CD80/86 on APC (it is a fusion protein)

Question 10

Side effects of Belatacept?

Answer 10

PTLD (post transplant lymphoproliferative disorder) in EBV seronegative pts

Question 11

What are the calcineurin inhibitors?

Answer 11

Cyclosporine and Tacrolimus

Question 12

MOA of cyclosporine?

Answer 12

binds to cyclophillin and thereby decreases calcineurin activity –> decreases IL-2 transcription

Question 13

MOA of tacrolimus?

Answer 13

binds to FK506 and thereby decreases calcineurin activity –> decreases IL-2 transcription

Question 14

Side effects of cyclosporine/tacrolimus?

Answer 14

nephrotoxicity, increased renal vascular resistance, thrombotic microangiopathy (endothelial injury), HTN, gingival hyperplasia (cyclosporine), hyperlipidemia, diabetes, neurotoxicity, gout

Question 15

Post transplant diabetes is associated with use of what drugs?

Answer 15

steroids and calcineurin inhibitors (tacrolimus > cyclosporine)

Question 16

What are the antimetabolites?

Answer 16

Mycophenolate mofetil (MMF) and Azathioprine (AZT)

Question 17

MOA of mycophenolate mofetil/azathioprine?

Answer 17

inhibit purine synthesis and lymphocyte growth (T and B cells)

Question 18

Side effects of mycophenolate mofetil/azathioprine?

Answer 18

diarrhea, nausea, vomiting, leukopenia, anemia, thrombocytopenia; pancreatitis (azathioprine)

Question 19

What is the mTOR inhibitor?

Answer 19

rapamycin (sirolimus)

Question 20

MOA of rapamycin (sirolimus)?

Answer 20

binds FK506 and thereby inhibits mTOR and IL-2 signaling

Question 21

Side effects of rapamycin (sirolimus)?

Answer 21

severe hyerlipidemia, oral ulcerations, pneumonitis and interstitial lung disease, impair wound healing, lymphocele

Question 22

What is the corticosteroid?

Answer 22

prednisone

Question 23

MOA of prednisone?

Answer 23

inhibits transcription of inflammatory mediators (inhibits NFkB)

Question 24

Side effects of prednisone?

Answer 24

glucose intolerance, hypertension, weight gain, hyperlipidemia, osteoporosis, cataracts, gastritis

Question 25

What agents increase CNI levels?

Answer 25

macrolides (except azithromycin), non dihydropyridine CCBs (diltiazem, verapamil), antifungals (ketoconazole, fluconazole, voriconazole, itraconazole), protease inhibitors, amiodarone, grapefruit juice

Question 26

What agents decrease CNI levels?

Answer 26

rifampin, phenytoin, phenobarbital, carbamazepine, St. John Wort

Question 27

How do you treat cellular rejection?

Answer 27

Steroids, ATG (kills T cells)

Question 28

How do you treat antibody mediated rejection?

Answer 28

Steroids, Plasmapheresis, IVIG, Bortezomib (proteasome inhibitor)

Question 29

CMV prophylaxis?

Answer 29

Valganciclovir for 3 - 6 months

Question 30

Pneumocystis pneumonia (PCP) prophylaxis?

Answer 30

Bactrim/Pentamidine/Atovaguone for one year

Question 31

Fungal prophylaxis?

Answer 31

Nystatin/clotrimazole for 2 - 4 weeks