Therapeutics Iii Exam 3 - Intro To Organ Transplant Questions

Front 1

What is a xenograft?

Back 1

A transplant of organs or tissue from one species to another.

Front 2

What are the types of organs that can be transplanted?

Back 2

-kidney (deceased or living related donors)
-liver (deceased or living donor)
-pancreas
-heart (deceased donor)
-small bowel (deceased donor)
-lung (deceased donor)

Front 3

What are some absolute contraindications to organ donation?

Back 3

-chronic renal disease
-over age 70
-potentially metastasizing malignancy
-severe hypertension
-untreated bacterial sepsis
-current IV drug abuse
-hepatitis B surface antigen positive
-HIV positive
-prolonged warm ischemia (down time)

Front 4

What are some general contraindications to organ transplant?

Back 4

-obesity (BMI over 35)
-uncontrolled infection
-malignancy (must be cancer free for 2 years)
-continued substance abuse
-poor family/social support
-uncontrolled psychiatric disorder
-medical noncompliance

Front 5

What are some factors affecting graft survival?

Back 5

-cold ischemic time
-retransplantation
-race (worse for blacks)
-age
-HLA mismatches (kidney only)
-PRA - panel reactive antibody (kidney only)
-delayed graft function
-multiple early rejection episodes
-compliance/adherence

Front 6

What are the goals of immunosuppression in organ transplant?

Back 6

-prevent acute rejection and graft loss
-minimize drug induced toxicity and side effects
-maintain long-term patient and graft survival
-reduce/discontinue immunosuppressive agents over time

Front 7

What is the purpose of induction agents?

Back 7

They are given in the perioperative period and provide potent, immediate immunosuppressive effects. They allow delayed initiation of the nephrotoxic maintenance immunosuppression.

Front 8

What are some advantages and disadvantages of induction agents?

Back 8

Advantages are that they deplete or block circulating T lymphocytes. A major disadvantage is cost.

Front 9

What are the induction agents available for use?

Back 9

-IL-2 receptor antibodies (monoclonal)
-Antithymocyte globulins (polyclonal)
-High dose IV steroids (methylprednisolone)
-Mycophenolate Mofetil
-Alemtuzumab

Front 10

What is the dose and MOA of methylprednisolone?

Back 10

It is the universal agent given with almost all transplants (except pancreas). Give 500mg IVPB preoperatively. It works by decreasing IL-2 production.

Front 11

What are the IL-2 receptor antagonists and what is their MOA?

Back 11

-basiliximab and daclizumab
They block interleukin-2 receptor on activated T lymphocytes. This stops the cell cycle of immune cells.

Front 12

What is the dose of basiliximab?

Back 12

20 mg IVPB on day 0 and day 4

Front 13

What is the MOA of polyclonal antibodies: antithymocyte globulins?

Back 13

They bind to T-cell receptors and deplete circulating lymphocytes through direct cytotoxicity.

Front 14

What is the main antithymocyte globulin (polyclonal antibody) used?

Back 14

ATG (rabbit)

Front 15

What is the dose of ATG?

Back 15

1.5mg/kg for 10-14 days through a high flow vein

Front 16

What are the adverse effects of ATG?

Back 16

-fever, chills (flu in a bottle)
-leukopenia, thrombocytopenia
-skin rash, serum sickness
-infection
-all cases are worst on the first dose

Front 17

What is the common induction regimen for kidney transplant patients?

Back 17

-methylprednisolon 500 mg IVPB x 1
-MMF 2 grams IVPB x 1
-basiliximab 20 mg IVPB on days 0 and 4

Front 18

What is the common induction regimen for liver transplant patients?

Back 18

methylprednisolone 500mg IVPB x 1

Front 19

What is an alternative induction regimen for kidney transplant patients at high immunological risk?

Back 19

-ATG 2mg/kg on days 0, 1, and 3
-methylprednisolone 500mg IVPB x 1
-MMF 2gm IVPB x 1

Front 20

What is a steroid free induction regimen?

Back 20

alemtuzumab (Campath) 30mg IVPB x 1
It is usually only used in pancreas transplant.

Front 21

How does alemtuzumab work?

Back 21

It binds to CD52 antigen present on B and T lymphocytes, monocytes, macrophages, and NK cells. It affects both adaptive and innate immunity. Therefore, it works all across the immune cell cycle and depletes many immune cells.

Front 22

What are the main maintenance immunosuppressants?

Back 22

The calcineurin inhibitors: cyclosporine and tacrolimus

Front 23

What is the MOA of cyclosporine?

Back 23

It is a calcineurin inhibitor. It preferentially inhibits antigen-triggered T-cell activation and inhibits the expression of many lymphokines including IL-2. (Calcineurin dephosphorylates NFAT, which stimulates IL-2 production)

Front 24

What is the dose of cyclosporine?

Back 24

Ranges from 7-10mg/kg in two divided doses (250-500 mg BID). IV dose is 1/3 of oral dose. Dose to level ratio is linear. Doubling the dose will double the level in the body.

Front 25

What should the cyclosporine level be 1-29 days post-transplant?

Back 25

300-350 ng/ml

Front 26

What should the cyclosporine level be 30-89 days post-transplant?

Back 26

250-300 ng/ml

Front 27

What should the cyclosporine level be 90-365 days post-transplant?

Back 27

200-250 ng/ml

Front 28

What should the cyclosporine level be over 1 year post-transplant?

Back 28

100-150 ng/ml

Front 29

How is cyclosporine metabolized?

Back 29

cyclosporine is extensively hepatically metabolized leading to many CYP3A4 reactions

Front 30

What are unique cyclosporine adverse effects?

Back 30

-hyperlipidemia
-gingival hyperplasia
-hirsutism

Front 31

What is the dose of tacrolimus?

Back 31

3 mg BID
dose adjustments are based on 12 hour trough levels

Front 32

What should the tacrolimus level be at 1-29 days post-transplant?

Back 32

10-15 ng/ml

Front 33

What should the tacrolimus level be at 30-89 days post-transplant?

Back 33

8-12 ng/ml

Front 34

What should the tacrolimus level be at 90-365 days post-transplant?

Back 34

5-10 ng/ml

Front 35

What should the tacrolimus level be at over 1 year post-transplant?

Back 35

5-8 ng/ml

Front 36

What adverse reactions are unique to tacrolimus?

Back 36

-diabetes mellitus
-alopecia

Front 37

What are the major side effects of calcineurin inhibitors?

Back 37

-cardio - HTN and hypercholesterolemia
-glucose intolerance
-nephrotoxicity
-malignancy (incidence appears to be a function of the overall exposure to immunosuppression rather than any specific agent)

Front 38

What monitoring is necessary with calcineurin inhibitors?

Back 38

-drug concentrations (trough)
-liver function
-renal function
-blood pressure
-blood glucose
-electrolytes

Front 39

What are the main drugs that increase calcineurin inhibitor levels?

Back 39

-calcium channel blockers (verapamil and diltiazem; use nifedipine instead)
-azole antifungals (reduce dose by 50% unless using tacrolimus + voriconazole then reduce dose by 66%)
-macrolide antibiotics

Front 40

What are the main drugs that decrease calcineurin inhibitor levels?

Back 40

-Anti TB agents (rifampin, rifabutin, isoniazid)
-Anticonvulsants (barbiturates, phenytoin, carbamazepine)
-St. John's wort

Front 41

Which drugs potentiate the toxic effects of calcineurin inhibitors?

Back 41

-nephrotoxic agents (NSAIDs, aminoglycosides, amphotericin)
-antacids
-statins
-IV contrast

Front 42

What are the adjuvant agents used for immunosuppression?

Back 42

-antiproliferative agents (azathioprine, mycophenolate mofetil, mycophenolic acid)
-mTOR inhibitors (sirolimus, everolimus)
-corticosteroids (prednisone)

Front 43

What is the MOA of azathioprine?

Back 43

inhibits cellular purine synthesis

Front 44

What is the dose of azathioprine?

Back 44

50-100 mg daily

Front 45

What are the major adverse effects of azathioprine?

Back 45

-leukopenia, anemia, pancytopenia, thrombocytopenia
-monitor WBC (if WBC are 3000-5000 or platelets are below 100,000 then reduce dose 50%; if WBC are below 3000 or platelets are below 50,000 then d/c drug until problem resolves)
-hepatotoxicity
-increased risk of malignancy

Front 46

What are drug interactions with azathioprine?

Back 46

allopurinol (reduce AZA dose by 1/3-1/4 of the normal dose)

Front 47

What is the MOA of mycophenolate?

Back 47

It is a reversible inhibitor or IMPDH. IMPDH is a key enzyme in the de novo pathway for the synthesis of guanine nucleotides. It is primarily found in proliferating B and T lymphocytes. Other cells in the body can use the de novo pathway and/or salvage pathways. Mycophenolic acid is therefore a selective inhibitor of lymphocyte proliferation.

Front 48

Why is mycophenolate used?

Back 48

It is used in conjunction with a calcineurin inhibitor and corticosteroids. It allows for lower doses of CNI in effort to reduce CNI associated toxicity. It increases graft survival and has less myelosuppression.

Front 49

What is the conversion of mycophenolate mofetil and mycophenolic acid?

Back 49

1 g BID of mycophenolate mofetil equals 720 mg BID or mycophenolic acid

Front 50

What are the adverse effects of mycophenolate?

Back 50

nausea
diarrhea
*both dose dependent

Front 51

What is the only mTOR inhibtor?

Back 51

sirolimus

Front 52

What is the MOA of sirolimus?

Back 52

Sirolimus inhibits T-cell activation downstream of the IL-2 receptor. It binds to and inhibits a protein kinase, mTOR, which is a key enzyme in cell-cycle progression. Sirolimus inhibits cell-cycle in all rapidly dividing cells.

Front 53

What is the dose of sirolimus?

Back 53

6 mg loading dose followed by 2 mg daily maintenance

Front 54

What are adverse effects of sirolimus?

Back 54

-hypercholesterolemia, hypertriglyceridemia
-lymphocele (cystic mass containing lymphatic drainage)
-poor wound healing - never start just after transplant due to surgical wound
-pneumonitis

Front 55

What are the therapeutic levels of sirolimus?

Back 55

10-15ng/ml (if patient is on CSA)
12-24ng/ml (if on sirolimus as primary immunosuppressant)
-administer sirolimus 4 hours after CSA

Front 56

What are drug interactions with corticosteroids?

Back 56

CYP3A4 inducers

Front 57

What are adverse effects of corticosteroids?

Back 57

-Endocrine: glucose intolerance, hyperglycemia, hyperlipidemia, osteoporosis
-Skin/appearance: Na/fluid retention, weight gain, impaired wound healing
-Other: HTN, infection, peptic ulcer disease (prophylax)

Front 58

What are the most common immunosuppressant regimens?

Back 58

CSA/MMF/Pred
TAC/MMF/Pred

Front 59

What are the most common maintenance immunosuppressant therapies for kidney transplant?

Back 59

TAC/myfortic/prednisone
CSA/myfortic/prednisone (high risk for NODAT)

Front 60

What is the most common maintenance immunosuppressant therapy for liver transplant?

Back 60

TAC/myfortic/prednisone