Immunosuppresants

Question 1

Calcineurin inhibitor; binds cyclophilin. Blocks T-cell activation by preventing IL-2 transcription.

Answer 1

Cyclosporine

Question 2

What toxicity associated with Cyclosprine?

When do we use it?

Answer 2

Toxicity: Nephrotoxicity, hypertension, hyperlipidemia, neurotoxicity, gingival hyperplasia, hirsutism.

Use: Transplant rejection prophylaxis, psoriasis, rheumatoid arthritis.

Question 3

Calcineurin inhibitor; binds FK506 binding protein (FKBP).

Blocks T-cell activation by preventing IL-2 transcription

Answer 3

Tacrolimus

Use: Transplant Rejection

Question 4

What is the side effect profile of Tacrolimus?

Answer 4

Use: prophylaxis for transplant rejection

HIGH risk of NEPHROTOXICITY and increase risk of diabetes and neurotoxic

Question 5

What two drugs prevent IL-2 transcription and are calcineurin inhibitors?

Answer 5

Cyclosporine: calcinurin inhibitor; no IL-2 NO T cell activation

Tacrolimus: calcinurin inhibotor by binding FK506: no IL-2, NO T cell activation

Question 6

mTOR inhibitor; binds FKBP.

Blocks T-cell activation and B-cell differentiation by preventing response to IL-2

Answer 6

Sirolimus: for kidney transplant rejection prophy

Question 7

What side effects do we see in Siroliumus?

What calcinurein inhbitor does it work synergistically with?

MOA?

Answer 7

Anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia; not nephrotoxic.

Works with Cyclosprine

mTOR inhibitor; binds FKBP. Blocks T-cell activation by preventing IL-2 transcription.

Question 8

Monoclonal antibodies; block IL-2R.

For Kidney transplant rejection prophylaxis.

Answer 8

Daclizumab, basiliximab

see edema

Question 9

Antimetabolite precursor of 6-mercaptopurine.: Inhibits lymphocyte proliferation by blocking nucleotide synthesis.

Drug?

uses?

Drug interactions?

Answer 9

Azothiprine: leukopenia and anemia

transplant rejection prophylaxis, rheumatoid arthritis, Crohn disease, glomerulonephritis, other autoimmune conditions.

6-MP degraded by xanthine oxidase; toxicity 􏰁 by allopurinol.

Pronounce “azathio- purine.”

Question 10

Mechanims of Glucocorticoids

Side effects

Answer 10

Inhibit NF-κB. Suppress both B- and T-cell function by 􏰀DECREASING transcription of many cytokines.

Sides: Hyperglycemia, osteoporosis, central obesity, muscle breakdown, psychosis, acne, hypertension, cataracts, avascular necrosis.

Question 11

Inhibit NF-κB. Suppress both B- and T-cell function by 􏰀DECREASING transcription of many cytokines.

Answer 11

Glucocortocoids

Question 12

When would we use

Filgrastim (G-CSF)

Sargramostim (GM-CSF)

Answer 12

For recovery of bone marrow

Question 13

What pts would benefit from using INF-Alpha

Answer 13

Chronic hepatitis B and C, Kaposi sarcoma, malignant melanoma

Question 14

What pts benefit from INF-gamma?

What about INF- B?

Answer 14

INF-gamma = Chronic granulomatis disease

INF-B = MS

Question 15

What are INfliximab and Adalimumab used for?

Mechanims?

Answer 15

Soluble TNF-Alpha antiBody

Uses: IBD, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 16

Natalizumab

MOA?

Uses

Answer 16

MOA: soluble α4-integrin antiB

Uses: Multiple sclerosis, Crohn disease

Sides: α4-integrin: WBC adhesion Risk of PML in patients with JC virus

Question 17

Antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention

MOA: Platelet glycoproteins IIb/IIIa antiBody

Answer 17

Abciximab

IIb times IIIa equals “absiximab”

Question 18

Treats Osteoporosis; i_nhibits osteoclast maturation_ (mimics osteoprotegerin)

Answer 18

Denosumab : antiB for RANLK

Denosumab affects osteoclasts

Question 19

Allergic asthma; prevents IgE binding to FcεRI

Answer 19

Omalizumab