Immunosuppressants Flashcards
Gluocorticoids MOA
Genomic: Bind to cytosolic receptor and translocating to nucleus to bind to DNA
Non-genomic: Insert themselves into cell membrane, influence signaling pathways, etc.
Gluocorticoids MOA
Genomic: Bind to cytosolic receptor and translocating to nucleus to bind to DNA
Non-genomic: Insert themselves into cell membrane, influence signaling pathways, etc.
Glucocorticoid effects
Rapid decrease in peripheral lymphocytes
Decrease pro-inflammatory cytokines=> IL-1, IL-6, TNFa, Infy
Inhibit IL-2 production by T cells
Little effect on humoral immunity
Glucocorticoid therapeutic uses
Treat transplant rejection, usually co administered with something else
Treat graft vs host disease
Blocks first dose cytokine storm
Treat autoimmune disorders
Glucocorticoids adverse
Increased risk of infection
Poor wound healing
HTN
Adrenal crisis upon discontinuation
Low dose glucocorticoids
Medium dose glucocorticoids
> 7.5 mg, but
High dose glucocorticoids
> 30 mg, but
Glucocorticoids pulse therapy
> 250 mg prednisone equivalent per day for 1 day or a few days
Glucocorticoids pulse therapy
> 250 mg prednisone equivalent per day for 1 day or a few days
Glucocorticoid effects
Rapid decrease in peripheral lymphocytes
Decrease pro-inflammatory cytokines=> IL-1, IL-6, TNFa, Infy
Inhibit IL-2 production by T cells
Little effect on humoral immunity
Glucocorticoid therapeutic uses
Treat transplant rejection, usually co administered with something else
Treat graft vs host disease
Blocks first dose cytokine storm
Treat autoimmune disorders
Glucocorticoids adverse
Increased risk of infection
Poor wound healing
HTN
Adrenal crisis upon discontinuation
Low dose glucocorticoids
Medium dose glucocorticoids
> 7.5 mg, but
Azathrioprine class and MOA
Purine antimetabolite
Metabolized into 6-mercaptopurine->other metabolites, incorporated into DNA, inhibiting lymphocyte proliferation
Lymphocytes do not have a salvage pathway=>cannot compensate
Very high dose glucocorticoids
> 100 mg prednisone equivalent per day
Glucocorticoids pulse therapy
> 250 mg prednisone equivalent per day for 1 day or a few days
Cyclosporine class and MOA
Calcineurin inhibitor
Suppresses T-cell mediated immunity by forming a complex w/ cyclophilin=>binds to and inhibits calcineurin=>IL-2 (T cell growth factor) is not produced
Cyclosporine uses
Very effective for prophylaxis for organ transplants, except for renal transplants b/c it is nephrotoxic
Cyclosporine adverse
Renal dysfunciton HTN Hyperlipidemia Swollen/painful gums Hirsutism Do not drink grapefruit juice
Tacrolimus class and MOA
Calcineurin inhibitor
same MOA as cyclosporine
Tacrolimus uses
Prophylaxis of allograft rejection in solid-organ transplantation
Sirolimus adverse
Anemia/leukopenia/thrombocytopenia
hypokalemia
GI
Increased risk of infections
Azathioprine class adn MOA
Purine antimetabolite
Metabolized into 6-mercaptopurine->other metabolites, inserts into DNA, inhibiting lymphocyte proliferation
Lymphocytes do not have a salvage pathway=>cannot compensate
Azathriopine uses
Prevention of organ transplant rejection
Severe RA
Some autoimmune disorders
Azathriopine adverse
Bone marrow suppression=> leukopenia
hepatotoxicity
Increased susceptibility to infections
Mycophenolate Mofetil MOA
MMF is a prodrug, hydrolezed to MPA=>selective inhibitor of an enzyme required for synthesis of guanine =>destroys de novo pathway
Mycophenolate Mofetil uses
Transplant rejection
Lupus
Mycophenolate Mofetil adverse
leukopenia
Increased risk for CMV
Congenital abnormalities
Sirolimus MOA
Inhibits T-lymphocyte proliferation, blocks G1-S phase transition
Sirolimus Uses
Prophylaxis for organ transplant rejection
In renal transplant for pts who cannot tolerate calcineurin inhibitors
Sirolimus adverse
Anemia/leukopenia/thrombocytopenia
hypokalemia
GI
Increased risk of infections
Antithymocyte Globulin MOA
Contains antibodies from a rabbit that binds to things like CD3 (and much more CDs) to deplete human T lymphocytes
Antithymocyte Globulin uses
Induction immunosuppression
Tx of acute reaction of solid organ transplants
Antithymocyte Adverse
fevers, chills, malaise, hypotension due to release of cytokines (TNF-a)=> cytokine storm
Serum sickness
Murononab-CD3 MOA
Mouse antibody directed against CD3=> cause depletion of T lymphocytes
Muromonab-CD3 uses
Reverse glucocorticoid resistant organ transplant rejection episodes
Can only use this drug once!!
Muomonab-CD3 adverse
cytokine storm
tremor, nausea, weakness
Anti-TNFa reagants
Infliximab, adalimumab, and etanercept
Anti-TNFa MOA
prevents TNFa form binding to its receptors by binding to it directly
Infliximab
Monoclonal antibody that is part human and part murine (mouse)
Adalimumab
Recombinant human IgG1 monoclonal antibody
Etanercept
Part TNF-a receptor and part portion of human IgG1
Anti-TNFa uses
RA
Crohn’s
UC, spondylitis, etc
Anti-TNFa adverse
Increased risk for infections, lymphomas, and other malignancies
