immunosuppressants Flashcards
what are the indications for immunosuppressants?
transplantation - prophylaxis and acute rejection
autoimmune
inflammatory diseases
what are the major classes of immunosuppressive agents?
glucocorticoids
calcineurin inhibitors
antiproliferative / antimetabolic agents
biologicals
what are the adverse effects of immunosuppressive agents?
infectious disease
malignancy
what are the calcineurin inhibitors?
cyclosporine
tacrolimus
what are the antiproliferative / antimetabolic agents?
azathioprine
mycophenolate mofenil
sirolimus
what are the biological immunosuppressants?
antithymocyte globulin
muromonab-CD3
anti-TNFa
what are the general effects of glucocorticoids?
genomic - up to 1% of DNA influence via cytosolic receptors, inhibition of transcription factors
non-genomic - cell signaling pathways, cell membrane
what are the key specific effects of glucocorticoids?
- downregulation of proinflammatory cytokines (IL-1, IL-6)
- inhibit IL-2 (anti-T cell proliferation)
- decrease in peripheral WBCs
- reduce neutrophil chemotaxis
what are the adverse effects of glucocorticoids?
growth retardation increased risk of infection poor wound healing hypertension avascular necrosis of bone cataracts hyperglycemia adrenal crisis upon rapid discontinuation
what is considered a low dose of glucocorticoid?
below 7.5 mg prednisone equivalent per day
what is considered a medium dose of glucocorticoid?
7.5 - 30 mg prednisone equivalent per day
what is considered a high dose of glucocorticoid?
30 - 100 mg prednisone equivalent per day
what is considered a very high dose of glucocorticoid?
over 100 mg prednisone equivalent per day
what is considered pulse therapy for glucocorticoid?
over 250 mg per day for 1 day or a few days
what drug is the standard for glucocorticoid dosing regimens?
prednisone
what is the MOA of cyclosporine?
- suppresses T cell immunity
- forms complex with cyclophilin, which then binds to calcineurin and eventually leads to prevention of transcription and translation of certain cytokines
what is the main adverse toxicity associated with cyclosporine?
nephrotoxicity
what is the preferred calcineurin inhibitor for transplantation due to ease of blood level monitoring?
tacrolimus
what is the main therapeutic use for tacrolimus?
prophylaxis of allograft rejection in solid organ transplantation
what are the main adverse effects of tacrolimus?
nephrotoxicity
HTN
diabetes
grapefruit
what is the MOA of azathioprine?
- metabolized to 6-mercaptopurine
- metabolites incorporated into DNA
- inhibition of lymphocyte proliferation (lymphocytes do not have a salvage pathway)
what are the adverse reactions of azathioprine?
bone marrow suppression
hepatotoxicity
VZV, HSV
what is the MOA of mycophenolate mofetil?
- knock out de novo synthesis of guanine nts
2. inhibits lymphocyte proliferation
what are the therapeutic uses for mycophenolate mofetil?
propylaxis for graft rejection
SLE
what are the adverse reactions of mycophenolate mofetil?
hematologic
GI
contraindicated for pregnancy
what is the MOA of sirolimus?
inhibits T cell proliferation via prevation of mTOR activation
what drug has allowed combination use with cyclosporine and tacrolimus?
sirolimus
what is the main therapeutic use of sirolimus?
renal transplant patients that cant tolerate calcineurin inhibitors due to high-risk nephrotoxicity
what is the MOA of antithymocyte globulin?
- antibodies that bind to CDs (especially CD3) and HLAs on T cells
- depletion of circulating T cells via a) complement cytotoxicity and b) prevention of T cell activation
what is the MOA of muromonab CD3?
anti-CD3 antibodies cause depletion of T cells
what is the main therapeutic use of muromoab CD3?
reversal of glucocorticoid resistant organ transplant rejection episodes
what is the main adverse reaction of muromonab CD3?
cytokine storm
what is the MOA of the anti-TNFa reagents?
binds directly and prevents TNFa from binding to its receptors
what are the anti-TNFa agents?
infliximab
adalimumab
etanercept
what are the therapeutic uses of the anti-TNFa agents?
RA
IBD
what class of drug is cyclosporine?
calcineurin inhibitor
what class of drug is tacrolimus?
calcineurin inhibitor
what class of drug is azathioprine?
antiproliferative / antimetabolite
what class of drug is mycophenolate mofenil?
antiproliferative / antimetabolite
what class of drug is sirolimus?
antiproliferative / antimetabolite
what class of drug is antithymocyte globulin?
biologic
what class of drug is muromonab-CD3?
biologic
what class of drug is anti-TNFa?
biologic
