Immunosuppressants

Question 1

Cyclosporine: mech

Answer 1

Calcineurin inhibitor; binds cyclophilin.

Blocks T cell activation by preventing IL-2 transcription.

Question 2

Cyclosporine: use

Answer 2

Transplant rejection prophylaxis, psoriasis, rheumatoid arthritis.

Question 3

Cyclosporine: toxicity

Answer 3

Nephrotoxicity, HTN, hyperlipidemia, hyperglycemia, tremor, hirsutism, gingival hyperplasia

Question 4

Tacrolimus: mech

Answer 4

Caclineurin inhibitor; binds FK506 binding proteini (FKBP).

Blocks T cell activation by preventing transcription of IL-2.

Question 5

Tacrolimus: use

Answer 5

Transplant rejection prophylaxis, Atopic dermatitis

Question 6

Tacrolimus: tox

Answer 6

Increased risk of diabetes and neurotoxicity
GI distress, nephrotoxicity, HTN, hyperkalemia, hyperglycemia
Increased risk of lymphoma
Avoid grapefruit juice (increases tox)

Question 7

Sirolimus (Rapamycin): mech

Answer 7

mTOR inhibitor; binds FKBP

Blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction (response)

Question 8

Sirolimus (Rapamycin): use

Answer 8

Kidney transplant rejection prophylaxis

Question 9

Sirolimus (Rapamycin): tox

Answer 9

Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia
non-nephrotoxic**

Question 10

Sirolimus (Rapamycin): notes

Answer 10

Kidney “sir-vives”
Synergistic with cyclosporine.
Also used in drug-eluting stents

Question 11

Basiliximab, Daclizumab: mech

Answer 11

Monoclonal Ab; blocks IL-2R

Question 12

Basiliximab, Daclizumab: use

Answer 12

Kidney transplant rejection prophylaxis

Question 13

Basiliximab, Daclizumab: tox

Answer 13

Edema, HTN, tremor

Question 14

Azathioprine: mech

Answer 14

Antimetabolite precursor of 6-mercaptopurine.

Inhibits lymphocyte proliferation by blocking nucleotide synthesis

Question 15

Azathioprine: use

Answer 15

Transplant rejection prophylaxis, RA, Crohn disease, glomerulonephritis, other autoimmune conditions

Question 16

Azathioprine: tox

Answer 16

Leukopenia, anemia, thrombocytopenia

Question 17

Azathioprine: notes

Answer 17

6-MP degraded by xanthine oxidase; tox increased by allopurinol.

Question 18

Glucocorticoids: mech

Answer 18

Inhibits NF-kB

Suppresses both B and T cell function by decreasing transcription of cytokines

Question 19

Glucocorticoids: use

Answer 19

Transplant rejection prophylaxis, many autoimmune disorders, inflammation

Question 20

Glucocorticoids: tox

Answer 20

Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, HTN, cataracts, peptic ulcers.
Can cause iatrogenic Cushing’s syndrome
Can cause adrenal insufficiency –> dose should be tapered