Immunosuppressants

Question 1

Cyclosporine

Answer 1

Calcineurin inhibitor - binds to cytosolic protein cyclophilin before inhibiting calcineurin, a calcium-dependent serine-threonine phosphatase that normally activates T-cells by upregulating IL-2 receptors

Used for transplant rejection PPx, psoriasis, and RA

Toxicity: Nephrotoxicity, HTN, HLD, hyperglycemia, gingival hyperplasia, hirsutism

Question 2

Tacrolimus

Answer 2

Calcineurin inhibitor - binds FK506 binding protein before inhibiting calcineurin, a calcium-dependent serine-threonine phosphatase that normally activates T-cells by upregulating IL-2 receptors

Used for transplant rejection PPx

Toxicity: Nephrotoxicity, HTN, HLD, hyperglycemia, NO gingival hyperplasia or hirsutism (unlike cyclosporine)

Question 3

Sirolimus (Rapamycin)

Answer 3

mTOR inhibitor - binds FK506 binding protein before inhibiting mTOR, a serine-threonine protein kinase that is normally involved in IL-2 signal transduction (T cell activation and B cell differentiation)

Used for kidney transplant rejection PPx (synergistically with cyclosporine) and in drug-eluting stents

Toxicity: anemia, thrombocytopenia, leukopenia, insulin-resistance, HLD; non-nephrotoxic

Question 4

Basiliximab

Answer 4

Monoclonal antibody that blocks IL-2 receptors

Used in kidney transplant rejection PPx

Toxicities: edema, HTN, tremor

Question 5

Azathioprine

Answer 5

Antimetabolite precursor of 6-mercaptopurine, which inhibits PRPP amidotransferase (purine synthesis; “azathio-purine”)

Used in transplant rejection PPx, RA, Crohn disease, glomerulonephritis, other autoimmune conditions

Toxicity: leukopenia, anemia, thrombocytopenia; toxicity increased by allopurinol (6-MP normally degraded by xanthine oxidase)

Question 6

Glucocorticoids

Answer 6

Inhibit NF-kB, thereby suppressing both B and T cell function by decreasing transcirption of many cytokines

Used in transplant rejection PPx, inflammation, autoimmune disorders

Toxicities: iatrogenic Cushing syndrome, cataracts, peptic ulcers