Immunosuppressants

Question 1

Cyclosporine

Answer 1

Mechanism: binds to cyclophilins. Complex blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL-2 and its receptor

Clinical use: suppresses organ rejection after transplantation; selected autoimmune disorders

Toxicity: nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor, gingival hyperplasia, hirsutism

Question 2

Tacrolimus (FK-506)

Answer 2

Mech: binds to FK binding protein, inhibiting calcineurin and secretion of IL-2 and other cytokines

Clinical use: Potent immunosuppressive used in organ transplant recipients

Toxicity: nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, tremor

Question 3

Sirolimus (rapamycin)

Answer 3

Mech: inhibits mTOR. Inhibits T-cell proliferation in response to IL-2

Clinical use: immunosuppression after kidney transplantation in combination with cyclosporine and corticosteroids. Also used with drug-eluding stents

Toxicity: hyperlipidemia, thrombocytopenia, leukopenia

Question 4

Azathioprine

Answer 4

Mech: anti metabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes

Clinical use: kidney transplantation, autoimmune disorders (including glomerulonephritis and hemolytic anemia)

Toxicity: bone marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase; thus toxic effects may be increased by allopurinol

Question 5

Muromonab-CD3 (OKT3)

Answer 5

Mech: monoclonal antibody that binds to CD3 (epsilon chain) in the surface of T cells. Blocks cellular interaction with CD3 protein responsible for T cell signal transduction

Clinical use: immunosuppression after kidney transplantation

Toxicity: cytokine release syndrome, hypersensitivity reaction