Immunosuppresive Agents Flashcards
Cyclosporine
MOA: Calcineurin inhibitor. binds to cyclophilin protein–>complex inhibits calcineurin which blocks T cell activation by preventing IL-2 transcription
USES: transplant rejection prophylaxis, psoriasis, rheumatoid arthritis
TOXICITY: nephrotoxicity, HTN, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia
**calcineurin inhibitors are HIGHLY nephrotoxic
Tacrolimus
Calcineurin inhibitor. binds to FK506 binding protein–complex inhibits calcineurin which blocks T cell activation by preventing IL-2 transcription
USES: prophylaxis of transplant rejection
TOXICITY: nephrotoxicity, HTN, hyperlipidemia, hyperglycemia, tremor, (increased risk of diabetes compared to cyclosporine)
**highly nephrotoxic
Sirolimus
mTOR inhibitor; binds to FKBP and complex inhibits mTOR (kinase)–>inhibits T cell activation and B cell differentiation by preventing IL-2 signal transduction
USE: kidney transplant rejection prophylaxis
TOXICITY: anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia, NON-NEPHROTOXIC
Azathioprine
MOA: antimetabolite precursor of 6-mercaptopurine. Inhibits lymphocyte proliferation by blocking nucleotide synthesis.
USES: transplant rejection prophylaxis, rheumatoid arthritis, Crohn disease, glomerulonephritis, other autoimmune conditions
TOXICITY: 6-MP degraded by xanthine oxidase; toxicity increased by allopurinol.
Mycophenolate
Anti-proliferative agent
MOA: inhibits IMP dehydrogenase–> blocks de novo purine synthesis
PK: oral and IV; esterified prodrug, metabolized and excreted by liver
USES: prophylaxis of organ rejection in patients receiving kidney, heart, or liver transplants as part of combination therapy
TOXICITY: diarrhea, leukopenia, sepsis, opportunistic infections and secondary malignancies
Methotrexate
Anti-proliferative agent
MOA: inhibits dihydrofolate reductase; polyglutamated form inhibits thymidylate synthase (incorporation of dUTP into DNA)
PK: oral and IV; metabolized and excreted by liver
USES: management of selected adults with severe active RA, children with active polyarticular -course juvenile RA not responding to first line therapies; severe, recalcitrant, disabling psoriasis that is not responding to other therapies
TOXICITY: yell suppression,mucositis, acute renal failure, CNS effects, reproductive toxicity
Basiliximab
MOA: monoclonal antibody; blocks IL-2R
USES: kidney transplant rejection prophylaxis
TOXICITY: edema, HTN, tremor
Glucocorticoids
MOA: inhibit NF-kB. Suppress both B and T cell function by decreasing transcription of many cytokines
USES: transplant rejection prophylaxis (immune suppression), many autoimmune disorders, inflammation
TOXICITY: hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers
Epoetin Alfa
Erythropoietin
USE: anemia (especially in renal failure)
Thrombopoietin
Recombinant cytokines used for thrombocytopenia
Oprelvekin
Recombinant interleukin 11 used for thrombocytopenia
Filgrastim
Recombinant cytokine–granulocyte colony-stimulating factor used for recovery of bone marrow
Sargramostim
Granulocyte macrophage colony stimulating factor used for recovery of bone marrow
Aldesleukin
Recombinant interleukin 2 used for renal cell carcinoma, metastatic melanoma
IFN-alpha
Used to treat chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
