Immunosuppressants For Organ Transplant Flashcards
Classes of immunosuppressants and their uses
Protein based biologics: induction during or immediately after transplant to prevent acute rejection
Non-biologics: maintenance, to maintain viability of the organ
Glucocorticoids MOA and AE
MOA: binds GR to inhibit gene expression of pro-inflamm genes (IL2, TNFa), blocks prostaglandins
AE: infxn, stunt growth, osteopenia, wound healing, HTN, DM
What makes glucocorticoids even more diabetogenic
When combined with calcineurin inhibitors
Examples of cytotoxic antimetabolites
Azathioprine
MM
Main mechanism of cytotoxic antimetabolites
Inhibit clonal expansion of lymphocyte/T cell population
Azathioprine
MOA: 6MP/thiodGTP incorporated into DNA -> T/B cell supp
AE: myelosuppresion, drug intxn w/ allopurinol, Ace-i
Drug interaction between Azathioprine and Allopurinol
allopurinol inhibits XO metab of 6mp –> life threatening immunosuppresion (reduce aza dosage
Drug intxn between azathioprine and ACE-i
potentiated myelosuppression
Why should you consider genotyping patients who you are giving azathioprine to?
if inactive allele of TPMT, build up can lead to massive myelosuppression
Comparison in selectivity in MM vs azathioprine
MM is newer and more selective for suppressing immune cells
Mycophenolate mofetil MOA, AE
MOA: inhibits type 2 IMPDH in b/t cells –> suppressed
AE: diarrhea, vomit, leukopenia, birth defects
Dec dose with tacrolimus
List the calcineurin and mTOR inhibitors
Calcineurin: cyclosporine, tacrolimus
MTOR: sirolimus
Main mechanism of calcineurin/mTOR inhibitors
Block intracellular signaling in T cells to block activation and expansion
Calcineurin: blocks IL2
MTOR: blocks protein synthesis
Cyclosporine use, MOA, AE
Use: organ transplant
MOA: binds cyclophilin, inhib calcineurin, inactive NFAT, dec IL2
AE: RENAL, HTN, infections/malig
Tacrolimus MOA, AE
MOA: binds FKBP-12, calcineurin inhib, inactive NFAT, dec IL2
AE: WORSE renal, HTN, neurotoxicity
