Immunosuppresants

Question 1

Cyclosporine

Answer 1

Calcineurin inhibitor (binds cyclophilin)
Blocks T-cell activation by preventing IL-2 transcription

Use in transplant, psoriasis, Ra

Tox: nephrotocicity!!!! HTN, hyperlipidemia, neurotox, gingival hyperplasia, hirsutism

Question 2

Tacrolimus (FK506)

Answer 2

Calcineurin inhibitor (binds FK506 binding protein (FKBP))
Blocks T-cell activation by preventing IL-2 transcription

Tox: nephrotocicity!!!! neurotox!! HTN, hyperlipidemia

Question 3

Sirolimus (rapamycin)

Answer 3

mTOR inhibitor; binds FKBP
Blocks T and B cell activation by blocking response to IL-2

Use for kidney transplant prophylaxis

Tox: pancytopenia, insulin resistance, hyperlipidemia, NOT NEPHROTOXIC

Synergistic with cyclosporin; use in drug eluting stents

Question 4

Basiliximab

Answer 4

MAb to IL-2-R
Use for kidney transplant prophylaxis
Tox: edema, HTN, tremor

Question 5

Azathioprine

Answer 5

Antimetabolite precursor of 6-MP
Blocks nucleotide synth so also lymphocyte proliferation

USE: RA, CD, GN

TOX: pancytopenia

Degraded by XO, so increased toxicity in allopurinol pts

Question 6

Mycophenolate mofetil

Answer 6

Reversibly inhibits IMP dehydrogenase preventing purine synth.

USE: SLE nephritis

TOX: GI upset, pancytopenia, HTN, hyperglycemia, less nephro or neurotox

Assoc wit CMV infection

Question 7

Corticosteroids

Answer 7

Inhibit NF-kB; suppress B/T cell fxn by downreg. transcription of cytokines and inducing T-cell apoptosis

USE: autoimmunity, adrenal insufficiency, asthma, CLL, NHL

TOX: Cushing syndrome, osteoporosis, hypergly., DM, amenorrhea, adrenocortical atrophy, PUD, psychosis, catarracts, avascular necrosis

Demargination of WBC leads to artificial leukocytosis
Adrenal insuff with abrupt withdrawl