IP 850-Solid Organ Transplantation

Question 1

An antigen-presenting cell binds to the T-cell receptor and triggers the T cell at signal

Answer 1

1. Costimulator molecules and ligands bind at signal
2. The activation of both signals 1 and 2 are needed to result in the expression of interleukin-2 (IL-2) and other factors. At signal 3, stimulation of the IL-2 receptor on the T-cell surface triggers T-cell proliferation.

Question 2

Mechanisms of action of the available immunosuppressive medications include:

Answer 2

• blocking the production and release of cytokines from activated T cells
• downregulating and inhibiting T-cell surface receptors
• inhibiting T-cell proliferation
• and causing T-cell depletion

Question 3

Cylcosporine and tacrolimus inhibit

Answer 3

calcineurin

Question 4

The monoclonal antibody basiliximab bind and inhibits

Answer 4

the IL-2 receptor

Question 5

Azathioprine acts as

Answer 5

an antimetabolite to prevent T-cell proliferation

Question 6

Mycophenolate mofentil (MMF) and Mycophenolic acid (MPA) inhibit

Answer 6

purine synthesis, which prevents proliferation of T and B cells

Question 7

Sirolimus and everolimus inhibit

Answer 7

cytokine-stimulated T-cell proliferation

Question 8

Belatacept binds to

Answer 8

cluster of differentiation 80 (CD80) and cluster of differentiation 86 (CD86) receptors on the antigen-presenting cells, which prevents binding to cluster of differentiation 28 (CD28) on the T cell

Question 9

Alemtuzumab binds to

Answer 9

cluster of differentiation 52 (CD52), which is present on the surface of T and B cells.

Question 10

The goals of immunosuppression are to

Answer 10

1. prevent gait rejection
2. improve graft and patient survival
3. reduce complications
4. minimize medication adverse effects
5. improve overall patient quality of life
6. minimize the number of immunosuppressants that the patient receives for the duration of their life

Question 11

What are the 3 phases of immunosuppression?

Answer 11

Induction, Maintenance, and treatment of rejection

Question 12

MOA: Antithymocyte globulin

Answer 12

Blocks T-cell membrane proteins

Question 13

MOA: Alemtuzumab

Answer 13

Monoclonal antibody directed against the CD52 cell surface antigen

Question 14

MOA: Basiliximab

Answer 14

Chimeric monoclonal antibody against CD25

Question 15

MOA: Cyclosporine

Answer 15

Binds to cylophilin and forms complex that inhibits calcineurin

Question 16

MOA: Tacrolimus

Answer 16

Binds to FKBP12 and forms complex that inhibits calcineurin

Question 17

MOA: Azathioprine

Answer 17

Inhibits protein synthesis

Question 18

MOA: Mycophenolate

Answer 18

Inhibits inosine monophosphate dehydrogenase

Question 19

MOA: Sirolimus and Everolimus

Answer 19

Binds and forms complex with FKBP12 complex that inhibits mammalian target of rapamycin (mTOR)

Question 20

MOA: Belatacept

Answer 20

Selective T-cell costimulation blocker binds to CD80 and CD86 receptors on the antigen-presenting cell and prevents them from binding to CD28 on the T lymphocyte

Question 21

MOA: Corticosteroids

Answer 21

Block T-cell-derived and antigen-presenting cell-derived cytokine expression

Question 22

Antibody therapy includes

Answer 22

1. T-cell-depleting (used for the treatment of rejection)

2. Non-depleting agents (divided into polyclonal and monoclonal agents)

Question 23

Polyclonal antithymocyte antibodies are

Answer 23

rabbit antithymocyte globulin (rATG) and horse antithymocyte globulin (hATG)

Question 24

Alemtuzumab is a

Answer 24

humanized monoclonal anti-CD52 antibody

Question 25

Induction with antibody therapy includes:

Answer 25

Antithymocyte Globulin, Alemtuzumab, and Basiliximab

Question 26

Maintenance Immunosuppression includes:

Answer 26

Calcineurin Inhibitiors, Antiproliferatives, Corticosteroids, mTOR inhibitors, and Belatacept

Question 27

AEs: Antithymocyte globulin

Answer 27

- Cytokine-release syndrome - Thrombocytopenia, leukopenia - Headache, dizziness - Abdominal pain, diarrhea, nausea - Dyspnea - Hypertension, peripheral edema - Hyperkalemia

Question 28

AEs: Alemtuzumab

Answer 28

- Anemia, neutropenia, thrombocytopenia - Infusion reactions - Infections (cytomegalovirus, Pneumocystis jiroveci pneumonia, herpes virus - Diarrhea, nausea, vomiting - Insomnia

Question 29

AEs: Basiliximab

Answer 29

- Comparable to placebo | - Constipation, nausea, abdominal pain, vomiting, diarrhea, dyspepsia

Question 30

AEs: Cyclosporine

Answer 30

- Nephrotoxicity - Hypertension - Hyperlipidemia - Neurotoxicity - Post Transplant diabetes - Hyperkalemia - Hypomagnesemia - Hirsutism - Gingival hyperplasia

Question 31

AEs: Tacrolimus

Answer 31

- Similar to cyclosporin except: 1. Fewer cardiovascular issues 2. Fewer cosmetic problems such as hirsutism and gingival hyperplasia 3. More post transplant diabetes 4. More neurotoxicity than cyclosporine

Question 32

AEs: Azathioprine

Answer 32

- Anemia, neutropenia, thrombocytopenia - Hepatotoxicity - Pancreatitis

Question 33

AEs: Mycophenolate

Answer 33

- Diarrhea, nausea, vomiting | - Leukopenia, thrombocytopenia, anemia

Question 34

AEs: Sirolimus and Everolimus

Answer 34

- Hypertension - Perpipheral edema - Hyperlipidemia - Anemia, thrombocytopenia - Headache - Proteinuria - Delayed wound healing - Interstitial lung disease - Mouth ulcers

Question 35

AEs: Belatacept

Answer 35

- Hypertension - Peripheral edema - Hyperkalemia, hypokalemia - Constipation, diarrhea, nausea, vomiting - Headache - Cough, fever - Post transplant lymphoproliferactive disease - Progressive multifocal leukoencephalopathy - Tuberculosis

Question 36

AEs: Corticosteroids

Answer 36

- Hyperglycemia - Hypertension - Hyperlipidemia - Increased risk of gastric ulcers - Risk of fungal and bacterial infections - Osteoporosis - Suppression of HPA axis - Psychosis

Question 37

Calcineurin inhibitor concentrations are increased with concomitant administration of:

Answer 37

1. Calcium Channel Blockers (eg, diltiazem) 2. Triazole antifungals (eg, ketoconazole, itraconazole, voriconazole) 3. Macrolide antibiotics (eg, erythromycin) 4. Prokinetic agents (eg, metoclopramide) 5. Other medications such as amiodarone, cimetidine, omeprazole, and protease inhibitors

Question 38

Calcineurin inhibitor concentrations are decreased with concomitant administration of:

Answer 38

1. Anticonvulsant (eg, carbamazepine, phenytoin, and phenobarbital) 2. Rifampin 3. St. John's wort

Question 39

Cyclosporine and Tacrolimus can also result in increased renal toxicity with concomitant use of

Answer 39

1. aminoglycoside 2. amphotericin B 3. diuretics 4. non-steroidal anti-inflammatory drugs

Question 40

Mycophenolate concentrations are decreased with the use of

Answer 40

1. antacids 2. iron 3. cholestyramine 4. rifamycins 5. sevelamer

Question 41

Mycophenolate concentrations are increased with use of

Answer 41

1. acyclovir 2. ganciclovir 3. valacyclovir 4. probenecid

Question 42

Black Box Warnings for both Sirolimus and Everolimus

Answer 42

-Increased risk of infections and malignancies | Sirolimus cautions against use in liver and lung transplant recipients due to safety and efficacy issues