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60 Cards in this Set
- Front
- Back
What is a xenograft?
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A transplant of organs or tissue from one species to another.
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What are the types of organs that can be transplanted?
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-kidney (deceased or living related donors)
-liver (deceased or living donor) -pancreas -heart (deceased donor) -small bowel (deceased donor) -lung (deceased donor) |
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What are some absolute contraindications to organ donation?
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-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) |
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What are some general contraindications to organ transplant?
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-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 |
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What are some factors affecting graft survival?
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-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 |
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What are the goals of immunosuppression in organ transplant?
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-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 |
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What is the purpose of induction agents?
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They are given in the perioperative period and provide potent, immediate immunosuppressive effects. They allow delayed initiation of the nephrotoxic maintenance immunosuppression.
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What are some advantages and disadvantages of induction agents?
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Advantages are that they deplete or block circulating T lymphocytes. A major disadvantage is cost.
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What are the induction agents available for use?
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-IL-2 receptor antibodies (monoclonal)
-Antithymocyte globulins (polyclonal) -High dose IV steroids (methylprednisolone) -Mycophenolate Mofetil -Alemtuzumab |
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What is the dose and MOA of methylprednisolone?
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It is the universal agent given with almost all transplants (except pancreas). Give 500mg IVPB preoperatively. It works by decreasing IL-2 production.
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What are the IL-2 receptor antagonists and what is their MOA?
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-basiliximab and daclizumab
They block interleukin-2 receptor on activated T lymphocytes. This stops the cell cycle of immune cells. |
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What is the dose of basiliximab?
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20 mg IVPB on day 0 and day 4
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What is the MOA of polyclonal antibodies: antithymocyte globulins?
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They bind to T-cell receptors and deplete circulating lymphocytes through direct cytotoxicity.
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What is the main antithymocyte globulin (polyclonal antibody) used?
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ATG (rabbit)
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What is the dose of ATG?
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1.5mg/kg for 10-14 days through a high flow vein
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What are the adverse effects of ATG?
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-fever, chills (flu in a bottle)
-leukopenia, thrombocytopenia -skin rash, serum sickness -infection -all cases are worst on the first dose |
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What is the common induction regimen for kidney transplant patients?
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-methylprednisolon 500 mg IVPB x 1
-MMF 2 grams IVPB x 1 -basiliximab 20 mg IVPB on days 0 and 4 |
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What is the common induction regimen for liver transplant patients?
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methylprednisolone 500mg IVPB x 1
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What is an alternative induction regimen for kidney transplant patients at high immunological risk?
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-ATG 2mg/kg on days 0, 1, and 3
-methylprednisolone 500mg IVPB x 1 -MMF 2gm IVPB x 1 |
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What is a steroid free induction regimen?
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alemtuzumab (Campath) 30mg IVPB x 1
It is usually only used in pancreas transplant. |
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How does alemtuzumab work?
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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.
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What are the main maintenance immunosuppressants?
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The calcineurin inhibitors: cyclosporine and tacrolimus
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What is the MOA of cyclosporine?
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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)
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What is the dose of cyclosporine?
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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.
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What should the cyclosporine level be 1-29 days post-transplant?
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300-350 ng/ml
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What should the cyclosporine level be 30-89 days post-transplant?
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250-300 ng/ml
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What should the cyclosporine level be 90-365 days post-transplant?
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200-250 ng/ml
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What should the cyclosporine level be over 1 year post-transplant?
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100-150 ng/ml
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How is cyclosporine metabolized?
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cyclosporine is extensively hepatically metabolized leading to many CYP3A4 reactions
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What are unique cyclosporine adverse effects?
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-hyperlipidemia
-gingival hyperplasia -hirsutism |
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What is the dose of tacrolimus?
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3 mg BID
dose adjustments are based on 12 hour trough levels |
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What should the tacrolimus level be at 1-29 days post-transplant?
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10-15 ng/ml
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What should the tacrolimus level be at 30-89 days post-transplant?
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8-12 ng/ml
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What should the tacrolimus level be at 90-365 days post-transplant?
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5-10 ng/ml
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What should the tacrolimus level be at over 1 year post-transplant?
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5-8 ng/ml
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What adverse reactions are unique to tacrolimus?
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-diabetes mellitus
-alopecia |
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What are the major side effects of calcineurin inhibitors?
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-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) |
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What monitoring is necessary with calcineurin inhibitors?
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-drug concentrations (trough)
-liver function -renal function -blood pressure -blood glucose -electrolytes |
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What are the main drugs that increase calcineurin inhibitor levels?
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-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 |
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What are the main drugs that decrease calcineurin inhibitor levels?
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-Anti TB agents (rifampin, rifabutin, isoniazid)
-Anticonvulsants (barbiturates, phenytoin, carbamazepine) -St. John's wort |
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Which drugs potentiate the toxic effects of calcineurin inhibitors?
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-nephrotoxic agents (NSAIDs, aminoglycosides, amphotericin)
-antacids -statins -IV contrast |
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What are the adjuvant agents used for immunosuppression?
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-antiproliferative agents (azathioprine, mycophenolate mofetil, mycophenolic acid)
-mTOR inhibitors (sirolimus, everolimus) -corticosteroids (prednisone) |
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What is the MOA of azathioprine?
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inhibits cellular purine synthesis
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What is the dose of azathioprine?
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50-100 mg daily
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What are the major adverse effects of azathioprine?
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-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 |
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What are drug interactions with azathioprine?
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allopurinol (reduce AZA dose by 1/3-1/4 of the normal dose)
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What is the MOA of mycophenolate?
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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.
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Why is mycophenolate used?
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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.
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What is the conversion of mycophenolate mofetil and mycophenolic acid?
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1 g BID of mycophenolate mofetil equals 720 mg BID or mycophenolic acid
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What are the adverse effects of mycophenolate?
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nausea
diarrhea *both dose dependent |
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What is the only mTOR inhibtor?
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sirolimus
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What is the MOA of sirolimus?
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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.
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What is the dose of sirolimus?
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6 mg loading dose followed by 2 mg daily maintenance
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What are adverse effects of sirolimus?
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-hypercholesterolemia, hypertriglyceridemia
-lymphocele (cystic mass containing lymphatic drainage) -poor wound healing - never start just after transplant due to surgical wound -pneumonitis |
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What are the therapeutic levels of sirolimus?
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10-15ng/ml (if patient is on CSA)
12-24ng/ml (if on sirolimus as primary immunosuppressant) -administer sirolimus 4 hours after CSA |
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What are drug interactions with corticosteroids?
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CYP3A4 inducers
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What are adverse effects of corticosteroids?
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-Endocrine: glucose intolerance, hyperglycemia, hyperlipidemia, osteoporosis
-Skin/appearance: Na/fluid retention, weight gain, impaired wound healing -Other: HTN, infection, peptic ulcer disease (prophylax) |
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What are the most common immunosuppressant regimens?
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CSA/MMF/Pred
TAC/MMF/Pred |
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What are the most common maintenance immunosuppressant therapies for kidney transplant?
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TAC/myfortic/prednisone
CSA/myfortic/prednisone (high risk for NODAT) |
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What is the most common maintenance immunosuppressant therapy for liver transplant?
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TAC/myfortic/prednisone
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