Immunosuppressants and Transplants (Rx)

Question 1

Describe Induction Therapy.

Answer 1

• Group biologic depleting agents and immune modulators.
• Delay the use of Calcineurin inhibitors
• Intensity of initial immunosuppressive therapy in high risk patients

Question 2

Describe Maintenance Therapy.

Answer 2

• use of multiple drugs to achieve synergistic effects
• calcineurin inhibitor, glucocorticoids, mycophenolate mofetil
• use protocols without steroids

Question 3

What is the therapy for established rejection.

Answer 3

Agents against T-cell functions

Question 4

Define the purpose of Calcineurin inhibitors. Provide 2 examples.

Answer 4

-Prevent transplantation rejection for kidney, liver, heart and other organs
-given IV/orally, peak: 1.5-2 hours at maintenance doses
-renal toxicity can occur with unfavorable drug interactions (p450 enzyme drugs)
Ex:) Cyclosporine and Tacrolimus

Question 5

Define mTOR inhibitors (purpose, admin, toxicity). Provide 2 examples.

Answer 5

-therapeutic uses: autoimmune conditions
-mTOR downstream of IL-2
-1 hour after oral administration
-dose-dependent increase in cholesterol/TG
-anemia/leukopenia
-affects CYP3A4 and enhances renal toxicity
Ex:) Sirolimus and Everolimus

Question 6

Define Cytotoxic drugs.

Answer 6

Medications that kill/ damage infected cells

Question 7

Describe Azathioprine.

Answer 7

• Prevents kidney rejection and can be given as a treatment for severe RA. Can also be used as an anti-cancer drug.
• MOA: inhibits DNA synthesis as a purine analogue
• toxicity: increased risk of neoplastic infections

Question 8

Define Mycophenolate Mofetil (MOA, clinical use and side effect).

Answer 8

• Cytotoxic drug that’s an inhibitor of IMP Dehydrogenase (reduces de novo purine synthesis; crippling to B and T cells that have no salvage pathway)
• approved for oral/IV use with corticosteroids and calcineurin inhibitors
• toxicity: GI disturbances, headaches, HTN and myelosuppression

Question 9

Define the purpose of immuno-suppressive antibodies. Provide 2 examples.

Answer 9

• Work against lymphocyte receptors
• Reduce lymphocyte/thymocyte activity
• Daclizumab monoclonal AB and Muromonab-CD3

Question 10

Define Daclizumab (Cx use, MOA, toxicity)

Answer 10

• Binds IL-2 receptor on activated T-cells to antagonize its function.
• used for acute renal transplant rejection
• lowers immunogenecity and immuno-suppressive

Question 11

Define Muromonab (Cx use, MOA, toxicity)

Answer 11

• Anti-CD3 antibody of T-cell receptor (depleting agent)
• Used for acute graft rejections, kills ONLY T-cells (cell-mediated suppression only)
• side effect: acute hypersensitivity and risk of infections

Question 12

Describe the purpose of immune checkpoint inhibitors.

Answer 12

• These drugs take the “brakes” off the immune system, which helps it attack cancer cells.
• Anti-PD1 antibodies (i.e. Nivolumab)

Question 13

Describe the purpose of glucocorticoids as immunosuppressants (MOA, Cx use and adverse effects)

Answer 13

• inhibit expression of cytokine genes (IL-1, IL-2, IL-6, interferon and TNF-alpha), T-cell proliferation and T-dependent immunity
• reduces INFLAMMATION, treats organ transplant rejection, autoimmune disorders, shock, asthma
• prolonged use = Cushingoid features, muscle wasting, increased risk of infections

Question 14

Describe the function of anti-TNF drugs and their clinical use. Provide an example.

Answer 14

• these are immunosuppressive antibodies that reduce TNF-alpha cytokines
• treats RA
• Ex) Infliximab, Adalimumab (Humira)

Question 15

If a physician is using immunosuppresants for a recent organ transplant patient, what should he keep in mind when using Calcineurin and mTOR inhibitors?

Answer 15

Space out use of cyclosporine and sirolimus administration to prevent renal toxicity from occuring.

Question 16

Define Acute Cellular rejection in context of a kidney transplant.

Answer 16

CD8+ T-cells infiltrate the transplanted organ and damage the tubular epithelium of the donor kidney.

Question 17

Define Chronic Rejection in context of a renal transplant.

Answer 17

Blood vessel thickening occurs after some time from the kidney transplant. This includes interstitial and glomerular fibrosis.

Question 18

Define Hyperacute rejection in context of a kidney transplant.

Answer 18

This type of rejection occurs within minutes in which fibrinoid necrosis and thrombosis can occur in the transplanted kidney. Pre-formed circulating antibodies result in a DIC reaction that forms fibrin thrombi.

Question 19

Describe Graft-vs-Host Disease (GVHD). What are the features?

Answer 19

If acute, this involves toxic transplanted CD8 T-cells that attack the recipient’s tissue. This can feature inflammation and fibrosis.

Question 20

Define the purpose of Infliximab (Remicade).

Answer 20

This is an anti-TNF-alpha drug that can be used as a treatment for rheumatoid arthritis.