Solid Organ Transplant Flashcards
Immunogenicity of various organs
Least to most: Liver Kidney Pancreas Heart Lungs GI
Induction therapy three main drugs
Basiliximab
Antithymocyte globulin
Alemtuzumab
Basliximab (Simulect) MOA
Blocks T-cell proliferation via IL-2 receptor antagonism (anti-CD25 antibody)
Lowest immunologic risk pts. and short MOA
Antithymocyte globulin (Thymoglobulin) MOA
Binds to T-cell surface antigens leading to the depletion of T-cells
Used in moderate immunologic patients
Alemtuzumab (Campath)
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
Maintenance therapy medications
Corticosteroids
Calcineurin inhibitors
Antimetabolites
mTOR inhibitors
Corticosteroids MOA
Inhibition of cytokine gene expression
Modification of lymphocyte distribution and fxn
Anti-inflammatory
Prednisone maintenance dosing
5-10 mg/day
Tacrolimus MOA
Inhibits T-cell activity through inhibition of IL-2 production
Tacrolimus metabolism
CYP3A4 (drug interxns) and p-glycoprotein (higher absorption with diarrhea)
Tacrolimus dosing
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
Tacrolimus therapeutic range
5-15 ng/mL
Cyclosporine MOA
Inhibits T-cell proliferation through inhibition of IL-2 production
Cyclosporine dosing
10-15 mg/kg/day in divided doses
Cyclosporine therapeutic range
50-200 ng/mL
Mycophenolate MOA
Inhibition of inosine monophosphate dehydrogenase (IMPDH) which inhibits de novo guanosine nucleotide synthesis
Prevents T and B lymphocytes proliferation
Mycophenolate dosing
250-1000 mg bid (MMF)
180-720 mg bid (Myfortic)
Conversion: 1000 mg Cellcept = 720 mg Myfortic
Mycophenolate precautions
Teratogenic, no pregnancy within one year
Azathioprine MOA and uses
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
Azathioprine dosing
3-5 mg/kg/day, then decrease to 1-3 mg/kg/day
Sirolimus MOA
Binds to FKBP-12 which inhibits mTOR leading to supression of cytokine T-cell proliferation
Sirolimus uses
May be used to replace mycophenolate or calcinerium inhibitor
Sirolimus dosing
1-5 mg/day to achieve target trough levels (same as tacrolimus)
Everolimus uses
Renal and heart transplant rejection prophylaxis.
Very expensive and just as effective as sirolimus
