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850-Exam 2 material > IP 850-Solid Organ Transplantation > Flashcards

IP 850-Solid Organ Transplantation Flashcards

1
Q

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

A
  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.
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2
Q

Mechanisms of action of the available immunosuppressive medications include:

A
  • 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
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3
Q

Cylcosporine and tacrolimus inhibit

A

calcineurin

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4
Q

The monoclonal antibody basiliximab bind and inhibits

A

the IL-2 receptor

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5
Q

Azathioprine acts as

A

an antimetabolite to prevent T-cell proliferation

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6
Q

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

A

purine synthesis, which prevents proliferation of T and B cells

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7
Q

Sirolimus and everolimus inhibit

A

cytokine-stimulated T-cell proliferation

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8
Q

Belatacept binds to

A

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

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9
Q

Alemtuzumab binds to

A

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

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10
Q

The goals of immunosuppression are to

A
  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
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11
Q

What are the 3 phases of immunosuppression?

A

Induction, Maintenance, and treatment of rejection

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12
Q

MOA: Antithymocyte globulin

A

Blocks T-cell membrane proteins

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13
Q

MOA: Alemtuzumab

A

Monoclonal antibody directed against the CD52 cell surface antigen

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14
Q

MOA: Basiliximab

A

Chimeric monoclonal antibody against CD25

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15
Q

MOA: Cyclosporine

A

Binds to cylophilin and forms complex that inhibits calcineurin

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16
Q

MOA: Tacrolimus

A

Binds to FKBP12 and forms complex that inhibits calcineurin

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17
Q

MOA: Azathioprine

A

Inhibits protein synthesis

18
Q

MOA: Mycophenolate

A

Inhibits inosine monophosphate dehydrogenase

19
Q

MOA: Sirolimus and Everolimus

A

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

20
Q

MOA: Belatacept

A

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

21
Q

MOA: Corticosteroids

A

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

22
Q

Antibody therapy includes

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

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

23
Q

Polyclonal antithymocyte antibodies are

A

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

24
Q

Alemtuzumab is a

A

humanized monoclonal anti-CD52 antibody

25
Q

Induction with antibody therapy includes:

A

Antithymocyte Globulin, Alemtuzumab, and Basiliximab

26
Q

Maintenance Immunosuppression includes:

A

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

27
Q

AEs: Antithymocyte globulin

A
  • Cytokine-release syndrome
  • Thrombocytopenia, leukopenia
  • Headache, dizziness
  • Abdominal pain, diarrhea, nausea
  • Dyspnea
  • Hypertension, peripheral edema
  • Hyperkalemia
28
Q

AEs: Alemtuzumab

A
  • Anemia, neutropenia, thrombocytopenia
  • Infusion reactions
  • Infections (cytomegalovirus, Pneumocystis jiroveci pneumonia, herpes virus
  • Diarrhea, nausea, vomiting
  • Insomnia
29
Q

AEs: Basiliximab

A
  • Comparable to placebo

- Constipation, nausea, abdominal pain, vomiting, diarrhea, dyspepsia

30
Q

AEs: Cyclosporine

A
  • Nephrotoxicity
  • Hypertension
  • Hyperlipidemia
  • Neurotoxicity
  • Post Transplant diabetes
  • Hyperkalemia
  • Hypomagnesemia
  • Hirsutism
  • Gingival hyperplasia
31
Q

AEs: Tacrolimus

A
  • 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
32
Q

AEs: Azathioprine

A
  • Anemia, neutropenia, thrombocytopenia
  • Hepatotoxicity
  • Pancreatitis
33
Q

AEs: Mycophenolate

A
  • Diarrhea, nausea, vomiting

- Leukopenia, thrombocytopenia, anemia

34
Q

AEs: Sirolimus and Everolimus

A
  • Hypertension
  • Perpipheral edema
  • Hyperlipidemia
  • Anemia, thrombocytopenia
  • Headache
  • Proteinuria
  • Delayed wound healing
  • Interstitial lung disease
  • Mouth ulcers
35
Q

AEs: Belatacept

A
  • Hypertension
  • Peripheral edema
  • Hyperkalemia, hypokalemia
  • Constipation, diarrhea, nausea, vomiting
  • Headache
  • Cough, fever
  • Post transplant lymphoproliferactive disease
  • Progressive multifocal leukoencephalopathy
  • Tuberculosis
36
Q

AEs: Corticosteroids

A
  • Hyperglycemia
  • Hypertension
  • Hyperlipidemia
  • Increased risk of gastric ulcers
  • Risk of fungal and bacterial infections
  • Osteoporosis
  • Suppression of HPA axis
  • Psychosis
37
Q

Calcineurin inhibitor concentrations are increased with concomitant administration of:

A
  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
38
Q

Calcineurin inhibitor concentrations are decreased with concomitant administration of:

A
  1. Anticonvulsant (eg, carbamazepine, phenytoin, and phenobarbital)
  2. Rifampin
  3. St. John’s wort
39
Q

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

A
  1. aminoglycoside
  2. amphotericin B
  3. diuretics
  4. non-steroidal anti-inflammatory drugs
40
Q

Mycophenolate concentrations are decreased with the use of

A
  1. antacids
  2. iron
  3. cholestyramine
  4. rifamycins
  5. sevelamer
41
Q

Mycophenolate concentrations are increased with use of

A
  1. acyclovir
  2. ganciclovir
  3. valacyclovir
  4. probenecid
42
Q

Black Box Warnings for both Sirolimus and Everolimus

A

-Increased risk of infections and malignancies

Sirolimus cautions against use in liver and lung transplant recipients due to safety and efficacy issues

850-Exam 2 material (19 decks)

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