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What are the 4 tests for transplant?
- Tissue matching (MHC)
- Blood type
- PRA
- Crossmatching
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How many alleles are checked on the MHC antigen for tissue matching?
6 alleles
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What is the term used when all 6 MHC alleles match between donor and recipient?
zero mismatched
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What is a Panel Reactive Antibodies (PRA) test used in transplants?
- Blood test for pre-formed anti-MHC antibodies against the lymphocytes from a population of donors
- Higher PRA indicates more chance of rejection
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What is crossmatching in transplants?
- Blood test performed shortly before the transplantation using blood from the donor and recipient to check for antibodies against the donor
- If donor's blood cells are destroyed, the test is positive and the recipient will almost certainly reject the transplant
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What are the types of graft rejection?
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What are the characteristics of a hyperacute graft rejection?
- Onset minutes to hours
- Quick loss of graft
- Prevention is the only treatment
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What are the characteristics of an acute graft rejection?
- Onset days to months
- Tissue biopsy needed to confirm
- Usually no loss of graft if managed successfully
- Therapy includes corticosteroids, polyclonal antibodies or monoclonal antibodies
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What are the characteristics of chronic graft rejection?
- Onset months to years
- Loss of graft
- Drug therapy often ineffective; consider re-transplantation
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What are the risk factors for acute graft rejection?
- Black
- Cadaveric donor
- Previous implants
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What drugs are used for transplantation?
- Prednisone
- Methylprednisolone
- Cyclosporine
- Tacrolimus
- Sirolimus
- Everolimus
- Azathioprine
- Mycophenolate mofetil (sodium salt not effective)
- Antithymocyte globulin (rabbit, horse)
- Daclizumab
- Basiliximab
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How many drugs are usually used for transplantation?
3 drugs
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Which drugs are used for induction therapy in transplantation?
- IV Corticosteroids (methylprednisolone, high dose)
- Calcineurin inhibitor
- Monoclonal antibody (Basiliximab or Daclizumab) - only for induction!
- Polyclonal antibody (Antithymocyte - rabbit or horse)
- Mycophenolate
- DO NOT use Sirolimus d/t delayed wound healing
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Which drugs are used for maintenance therapy in transplantation?
- Corticosteroid (usually Prednisone)
- Calcineurin inhibitor
- Mycophenolate mofetil
- Mycophenolic acid
- Azathioprine
- mTOR inhibitor
- PICK 1 drug from each of the 4 categories
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What are the special considerations for transplantation therapies?
- Separate Sirolimus and Cyclosporine by 4 hours to decrease potential risk for toxicities
- Tacrolimus:
- most commonly used calcineurin inhibitor in renal transplant
- more effective in decreasing incidence of acute rejections
- higher incidence of post-transplant DM
- less cosmetic effects
- Mycophenolate:
- used more than azathioprine in renal transplant d/t hepatotoxicity
- Corticosteroid dose may decrease over time and eventually stopped
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Which drugs are used for rejection therapy in transplantation?
- Acute:
- increase dose of current therapy
- Corticosteroid bursts
- Add a new immunosuppressant (but decrease current doses and start antibiotic prophylaxis - TMP/SMX, gancyclovir, nystatin, H2 blocker/PPI)
- Chronic:
- Prevent it through optimization of maintenance therapy
- re-transplant?
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What are the DI of Calcineurin inhibitors and mTOR inhibitors?
- Azoles
- Macrolides
- CCBs
- Statins
- Cimetidine
- TMP/SMX
- Grapefruit
- Seizure drugs
- TB meds
- St. John's Wort
- Cholestyramine (p-glycoprotein interaction)
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What are the complications of renal transplantation?
- Bleeding
- Wound infection
- Delayed graft function
- Graft dysfunction
- Graft rejection
- Drug-induced nephrotoxicity
- Cardiovascular/metabolic complications
- Endocrine dysfunction (bone, anemia, electrolytes)
- Myelosuppression
- GI ulceration/perforation
- Infections (less than other transplants)
- Post-transplant Lymphoproliferative Disorder (PTLD)
- Malignancies
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What is Post-transplant Lymphoproliferative Disorder (PTLD)?
- Uncontrolled proliferation of B-cells
- Potentially fatal
- Can progress to cancer (non-Hodgkin's)
- Usually associated with EBV, but not always
- Treatment:
- first-line - decrease doses of immunosuppressants
- alternative - Rituximab?
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What are some other considerations involved in the pharmacist's role in transplantation?
- No live vaccines
- No herbals (DI)
- Check with transplant team for OTCs
- Use high SPF sunblock
- Screen for DI
- Educate patient
- Be careful of water supply
- Use latex gloves when handling raw meat
- Wash all fruits and veggies
- Eat all meat well-done
- Avoid salad bars and buffet tables
- Carry meds when traveling, not in checked luggage
- Pets okay, but use caution
- Diet and exercise
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