Immunologic pharmacotherapies Flashcards
why are immunosuppressants frequently combined in therapeutic regimens
to increase efficacy with lower toxicity
what kind of immunity do immunosuppressants inhibit
cellular immunity; lymphocyte activation and proliferation is inhibited
what are the risks of chronic immunosuppression
infection and malignancy
what is the mechanism of action of cyclosporine
inhibits calcineurin by binding cyclophilin; blocks T cell activation by preventing IL-2 transcription
what is cyclosporine used to treat
transplant rejection prophylaxis, psoriasis, rheumatoid arthritis
what are the toxicities of cyclosporine
nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia
how does tacrolimus work
inhibits calcineurin by binding FK506 (FKBP) binding protein; blocks IL-2 transcription to prevent T-cell proliferation
what is tacrolimus used for
transplant rejection prophylaxis
what are the toxicities of tacrolimus
similar to cyclosporine, but no gingival hyperplasia or hirsutism (just nephrotoxicity, hypertension, hyperlipidemia, and hyperglycemia)
how does sirolimus (rapamycin) work
binds FKBP to inhibit mTOR; blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction
what is sirolimus (rapamycin) used for
kidney transplant rejection prophylaxis
what are the toxicities of rapamycin
edema, hypertension, tremor
how does azathioprine work
precursor of 6-mercaptopurine; inhibits lymphocyte proliferation by blocking nucleotide synthesis
what is azathioprine used for
transplant rejection prophylaxis, rheumatoid arthritis, Chron’s disease, glomerulonephritis, other autoimmune conditions
what are the toxicities of azathioprine
leukopenia, anemia, thrombocytopenia
what enzyme is responsible for degrading 6-MP and what drug blocks this enzyme leading to increased azathioprine toxicity
xanthine oxidase;
allopurinol increases toxicity by inhibiting xanthine oxidase
how do glucocorticoids acts as immunosuppresants
inhibit NF-kappaB to decrease cytokine transcription and thereby suppress both B and T cell function
what are glucocorticoids used for
transplant rejection prophylaxis (immune suppression), many autoimmune disorders, inflammation
what are the toxicities of glucocorticoids
hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts and peptic ulcers,
(iatrogenic Cushing’s)
what recombinant cytokine is used to treat anemias (especially in renal failure)
erythropoetin alpha
what two recombinant cytokines are used to treat thrombocytopenia
thrombopoietin and oprelvekin (interleukin 11)
which recombinant cytokines are used to treat bone marrow loss
filgrastim (G-CSF) and sargramostim (GM-CSF)
what is aldesleukin and what does it treat
aldesleukin (interleukin-2) is a recombinant cytokine and is used to treat renal cell carcinoma and metastatic melanoma
what is IFN-alpha used to treat
HBV, HCV (with ribavirin), Kaposi sarcoma, condyloma acuminatum, hairy cell leukemia, renal cell carcinoma, malignant melanoma
