Immunosuppressant Drugs Flashcards
Mechanism of cyclosporine
calcineurin inhibitor
binds cyclophilin
Blocks T-cell activation by preventing IL-2 transcription
Use of cyclosporine
transplant rejection prophylaxis, psoriasis, rheumatoid arthritis
Toxicity of cyclosporine
NEPHROTOXICITY
hypertension, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism
Mechanism of tacrolimus
calcineurin inhibitor
binds FK506 binding protein (FKBP)
blocks T-cell activation preventing IL-2 transcription
Use of tacrolimus
transplant rejection prophylaxis
Toxicity of tacrolimus
NEPHROTOXICITY
increased risk of diabetes and neurotoxicity
NO gingival hyperplasia and NO hirsutism
Mechanism of sirolimus
mTOR inhibitor that binds FKBP
blocks T-cell activation and B-cell differentiation by preventing response to IL-2
Difference between mechanism of cyclosporine/tacrolimus versus sirolimus in terms of IL-2
cyclosporine/tacrolimus prevent TRANSCRIPTION of IL-2
sirolimus prevents RESPONSE to IL-2
Use of sirolimus
kidney transplant rejection prophylaxis (because spares kidney)
synergistic with cyclosporine
Used in drug-eluting stents
Toxicity of sirolimus
anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia
NO nephrotoxicity
What are the IL-2R monoclonal antibodies?
Daclizumab and Basiliximab
Mechanism of daclizumab and basiliximab
monoclonal antibodies against IL-2R
Use of daclizumab and basiliximab
kidney transplant rejection prophylaxis
Toxicity of daclizumab and basiliximab
edema, hypertension, tremor
Mechanism of azathioprine
Antimetabolite precursor of 6-mercaptopurine
inhibits lymphocyte proliferation by blocking nucleotide synthesis
Use of azathioprine
transplant rejection prophylaxis, RA, Crohn’s disease, glomerulonephritis, autoimmune conditions
Toxicity of azathioprine
leukopenia, anemia, thrombocytopenia
Special consideration when using azathioprine
6-MP degraded by xanthine oxidase; toxicity increased by allopurinol which blocks xanthine oxidase
Do not use in GOUT patients on allopurinol or consider dose reduction
Mechanism of glucocorticoids
inhibit NF-kappaB
suppress both B and T cell function by decreased transcription of many cytokines
Use of glucocorticoids
transplant rejection prophylaxis (immunosuppression)
many autoimmune disorders
inflammation
Toxicity of glucocorticoids
Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, avascular necrosis
Can cause IATROGENIC Cushing syndrome
