Immunosuppressive Agents Flashcards
Indications for Induction Immunosuppressive Drugs?
transplant- organ, bone marrow
autoimmune conditions- SLE, RA
chronic rejection
Hypersensativity/Inflamm diseases- asthma, atopic dermatitis
mechanism of hyperacute rejection?
pre-formed antibodies
allo-antibodies (anti-MHC1)
within minutes
mechanism of acute rejection?
Cell-mediated (CD8)
antibody mediated
1-4 weeks later
mechanism of chronic rejection?
Cell-mediated (CD8)
antibody mediated
chronic renal allograft nephropathy
months-years laer
Principles of Immunosuppression?
target and block signals at different stages of T-cell activation
Induction immunosupp
intense, prophylactic
prevents acute rejection
at time of transplant
“puts immune system to sleep”
maintenance immunosupp
less potent
given throughout life of transplanted organ
prevents late acute rejection and graft survival
induction agents?
anti-lymphocyte globulin (thymoglobulin)
alemtuzumab
basiliximab
methylprednisone
MOA muronamab
CD3 blocker- signal 1
thymoglobulin MOA
“workhorse”
IgG antibodies bind T-cells, activate complement mediated cell lysis of circulation T-cells
thymoglobulin toxicity
fever, rash, pruritis
serum sickness- 7-14 days after
thrombocytopenia
pre-medicate with tylenol, benedryl
alemtuzumab MOA and tox
mab against CD52, used commonly with B-cell lymphoma
tox: injection site rxn, anemia, thrombocytopenia
basiliximab MOA
binds alpha unit of IL2 receptor, inhibiting binding–> decreased activation
very well tolerated
methylprednisone MOA
given in HIGH DOSE for INDUCTION
anti- inflammatory corticosteroid
blocks cytokine gene expression leading to decreased immune response
impair monocyte, macrophage function
methylprednisone tox
HTN, HYPERGLYCEMIA
impaired wound healing, fluid retention
vivid dreams
Note: taper into oral prednison for maintenence
Maintenance immunosupp drugs?
Tacromilus Cyclosporine Mycophenolate Azathioprine Siromilus Everolimus Prednisone
Tacromilus MOA
Calcineurin inhibitors- inhibit calcineurin phosphatase by binding FKBP12- downstream of signal 1
leads to INHIBITION IL2 synthesis
Tacromilus tox
alopecia, HYPERGLYCEMIA, hyperkalemia, NEPHROTOXICITY, FINE TREMOR at rest
CYP450 3A4 interactions
Mycophenolate/azathioprine MOA
Anti-metabolite
Inhibits prolif of B and T cells by preventing RNA/DNA synthesis in nucleus
Mycophenolate TOX
GI INTOLERANCE-diarrhea
azathioprine tox
Hepatotoxicity- not used
elevated ALT/AST
Sirolimus/Everolimus MOA
mTOR inhibition
Binds FKBP12- complex that inhibits target of rapamycin stopping prolif of B/T cells
inhibits IL2
Sirolimus TOX
ANEMIA, hepatic artery thrombosis, hyperlipidemia, IMPAIRED WOUND HEALING, PROTEINURIA
CYP450 3A4 interactions
prednisone MOA
LOW DOSE for maintenence-taper off
corticosteroid that blocks cytokine expression and decreases immune response
prednisone TOX
HYPERGLYCEMIA, OSTEOPOROSIS (supplement Ca)
Cyclosporine MOA
Calcineurin inhibitor- binds cyclophilin which inhibits calicineurin phosphatase, inhibiting IL2 synthesis
Cyclosporine TOX
same as tacromilus, but less potent, and has HIRSUTISM and HYPERTrICHOSIS
with less neurotox and hyperglycemia
when would you use mTOR?
with delayed graft function until kidney function kicks in underlying renal insufficiency other drug intolerance calcineurin toxicity pancreas transplant
typical maintenance regimen- kidney transplant?
tacromilus+mycophenolate+prednisone
typical maintenance regimen- liver transplant?
tacromilus+mycophenolate+/-prednisone
typical maintenance regimen- pancreas transplant?
tacromilus+ sirolimus OR mycophenolate
STEROID FREE b/c of HYPERGLYCEMIA RISK
