Immunosuppressive Medications

Question 1

what are the 5 main immunosuppressive medications?

Answer 1

• corticosteroids
• antiproliferative agents
• agents which block T cell activation
• antibodies
• fusion proteins

Question 2

Corticosteroids bind to GC receptors and NF-kappa-B (TF) in order to:

Answer 2

-upregulate and downregulate genes that result in:

immunosuppression and anti-inflammatory effects (macrophages, B cells, leukocytes)

Question 3

what are the most common corticosteroids used for immunosuppression?

Answer 3

• prednisone (oral)

- methylprednisolone (IV)

Question 4

What are the side effects of corticosteroids?

Answer 4

• infection: aggressive hep B, TB reactivation
• HTN
• hyperlipidemia
• glucose intolerance/ DM
• weight gain
• skin changes: fragility, striae, photosensitivity, acne
• osteopenia, osteoperosis
• avascular necrosis
• muscle atrophy/weakness
• cataracts
• poor wound healing
• mood changes
• accelerated atherosclerotic disease
• risk of adrenal insufficiency with prolonged use (ACTH feedback inhibition)

Question 5

List common antiproliferative agents (prevents proliferation of lymphocytes involved in autoimmunity/rejection):

Answer 5

• cyclophosphamide: prevent DNA synthesis/cell proliferation
• azathioprine: purine analog
• mycophenolic acid: block purine synthesis
• leflunomide: block pyrimidine synthesis
• methotrexate: block folic acid action

Question 6

what is the major toxicity of anti-proliferative agents?

Answer 6

Bone marrow suppression (rapidly dividing cells)

Question 7

what cancer treatment is commonly used for immunosuppresion?

what are the side effects?

Answer 7

cyclophsphamide: leukemia, lymphoma, breast cancer, ovarian cancer

SE: hematuria, neutropenia, ovarian failure, bladder cancer, leukemia

Question 8

what are SE of antiproliferative agents in general?

Answer 8

• neutropenia (due to suppression of cell proliferation)

- hepatotoxicity, pancreatitis, GI upset

Question 9

how does sirolumus work?

Answer 9

• mTOR inhibitor: prevents cytokine-dependent cell proliferation (block G1–> S transition)
• also prevents proliferation of some cancers (renal cancer)

Question 10

What are two major calcineurin inhibitors (CnI)?

How do they work?

Answer 10

• cyclosporine
• tacrolimus

block T cell response and decrease cytokine production and lymphocyte proliferation (prevents production of IL-2)

Question 11

what conditions are CnI good for treating?

Answer 11

• transplant
• glomerulonephritis
• psoriasis (topical)
• Rheumatoid arthritis
• ophthalmic disease (drops)

Question 12

How are monoclonal antibodies delivered for immunosuppressive therapy?

Answer 12

IV or SC

Question 13

how does the following mAb work: Basiliximab

Answer 13

• binds IL-2 receptor on T cell (alpha chain of CD25)–> T cell not activated
• prophylactic, not used after rejection

Question 14

how does the following mAb work: Infliximab

Answer 14

• anti-TNF alpha antibody, prevents TNF-alpha from binding to its receptor –> apoptosis of TNF-alpha expressing T cells
  uses: IBS, ankylosing spondylitis , psoriasis

Question 15

What polyclonal antibody is used for immunosuppression therapy?

How many antigens does it contain Abs against?

How does it work?

Answer 15

Thymoglobulin

(made by injecting human thymus into animal to stimulate Ab production)

• 40+ antigens
• T cell depletion mechanism, some activity against B cells and dendritic cells

Question 16

What is a main SE of thymoglobulin?

Answer 16

prolonged lymphopenia (CD4/CD8 ratio stays abnormal for many years after transplant)

Question 17

What is IVIg

Answer 17

-intravenous immunoglobulin

(pooled Ig from thousands of donors)

*doesn’t increase risk of infx or malignancy!

Question 18

What is IVIg used to treat?

Answer 18

• ITP
• Kawasaki disease
• myasthenia gravis
• chronic demyelinating polyneuropathy
• transplantation (rx rejection)

Question 19

How does IVIg work?

Answer 19

• inhibits Abs (Abs that inhibits Ab!)
• -inhibits complement
• inhibits B cells
• inhibits adhesion molecules

Question 20

What are fusion proteins?

Answer 20

They are proteins that join Fc part of Ab with receptor on target molecules–> prevents other molecules from binding to and activating the target molecule

• end in “-cept”

Question 21

What is Etanercept?

Answer 21

• a fusion protein
• TNF-alpha blocker: TNF receptor and Fc IgG: blocks TNFalpha from binding to WBC receptor
• treats: IBD

Question 22

What is abatacept/belatacept?

Answer 22

• fused Fc portion of IgG and extracellular domain of CTLA-4

- prevents costimulation of T cells (binds B7 on APC to prevent B7-CD28 interaction)

Question 23

What is often the first line rx of IBD?

Answer 23

5-ASA: 5-aminosalicylic acid (sulfa drug)

Question 24

What immunossupressive drug may cause macular toxicity and was originally an antimalarial drug?

Answer 24

Hydroxychloroquine

Question 25

What do the following mAb do to immune mediators? - alemtuzumab - rituximab - eculizumab - natalizumab

Answer 25

alemtuzumab: anti CD25 (lymphoma, depletes T and B cells) - rituximab: anti CD20 Ab (depletes B cells: lymphoma, rejection, glomerulonephritis, vasculitis) - eculizumab: mAb against C5 compliment protein (rejection) - natalizumab: anti alpha4 integrin Ab (MS, **risk of multifocal leukoencephalopathy)