Exam 6: Transplant Flashcards

1
Q

What is allograft rejection

A

immune response causing inflammation and direct tissue destruction

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2
Q

what is ACR

A

infiltration of the allograft by lymphocytes and other inflammatory cells

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3
Q

what is AMR

A
  1. circulating donor-specific antibodies

2. immunological evidence of an antibody-mediated process

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4
Q

hyperacute rejection

A

within minutes to hours after transplant

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5
Q

what mediates hyperacute rejection

A

preformed circulating antibodies

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6
Q

acute rejection

A

within days to months after transplant

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7
Q

what mediates acute rejection

A

host t-lymphocytes

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8
Q

chronic rejection

A

over months to years after transplans

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9
Q

what mediates chronic rejection

A

both cell-mediated and humoral processes

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10
Q

A blood type antigens

A

A antigens

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11
Q

A blood type antibodies

A

antibodies against B

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12
Q

B blood type antigens

A

B antigens

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13
Q

B blood type antibodies

A

antibodies against A

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14
Q

AB blood type antigens

A

A and B antigens

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15
Q

AB blood type antibodies

A

No antibodies AKA universal recipient

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16
Q

O blood type antigens

A

No antigens AKA universal donor

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17
Q

O blood type antibodies

A

Antibodies against A and B

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18
Q

ABO mismatch

A

Absolute CI for all deceased donor transplants

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19
Q

How does the immune system determine self vs non-self

A

HLA

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20
Q

HLA matching and outcomes

A

HLA matching= better outcomes

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21
Q

HLA antibodies

A

Do not occur naturally and are formed in response to non-self HLA exposure

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22
Q

Why is DSA testing used

A

To estimate risk of rejection and indicate failure of immunosuppression

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23
Q

Goals of immunosuppressive therapy

A
  1. Balance therapy in terms of graft and patient survival
  2. combination therapy
  3. individualized therapy
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24
Q

induction immunosuppressive agents

A
  1. thymoglobulin
  2. atgam
  3. campath
  4. simulect
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25
Q

which induction immunosuppressive agents are polyclonal antibodies

A
  1. thymoglobulin

2. atgam

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26
Q

which induction immunosuppressive agents are monoclonal antibodies

A

campath

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27
Q

which induction immunosuppressive agents are IL-2 receptor antagonists

A

simulect

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28
Q

antithymocyte globulin mechanism

A

reduces the number of cirulating t-lymphocytes and ultimately affects cell-mediated and humoral immunity- leading to lymphocyte depletion

29
Q

antithymocyte globulin duration

A

duration depends on indication and patient tolerance

30
Q

antithymocyte globulin AE

A

leukopenia, thrombocytopenia
fever, chills
tachycardia
pruritis

31
Q

antithymocyte globulin monitoring parameters

A

WBC, ALC, platelts

32
Q

campath mechanism

A
  • CD52 cell surface glycoprotein located on T and B lymphocytes, NK cells, and less densely on monocytes and macrophages
  • antibody dependent cellular cytotoxicity
  • profound depletion of T cells and to a lesser degree B cells and monocytes
33
Q

campath (alemtuzumab) AE

A

profound neutropenia, which is why it is off-labeled use

34
Q

simulect (basiliximab) mechanism

A

competitively inhibits IL-2 mediated activation of lymphocytes

35
Q

simulect AE

A

minimal

36
Q

DOC for lymphocyte depleting therapy, especially for patients with high immunologic risk

A

thymoglobulin, alemtuzumab

37
Q

DOC for non-lymphocyte depleting therapy: history of malignancy, high infection risk, immunocompromised, advanced aged

A

basiliximab

38
Q

Calcineurin inhibitors

A

cyclosporin

tacrolimus

39
Q

anitmetabolites

A

azathioprine

mycophenolate

40
Q

m-TOR inhibitor

A

sirolimus

everolimus

41
Q

corticosteroid

A

methylprednisolone

prednisone

42
Q

selective t-cell costimulation blocker

A

belatacept

43
Q

calcineurin inhibitor MOA

A

inducing immunosuppression by inhibiting signal-1 of t-cell activation

44
Q

tacrolimus formulations

A
  1. prograf
  2. astagraf
  3. envarsus
45
Q

prograf conversion

A

1 mg PO= 0.5 mg SL= 0.2mg IV

46
Q

envarsus conversion

A

1mg prograf= 0.8 mg envarsus

47
Q

Tacrolimus target trough

A

5-15 ng/ml

48
Q

cyclosporine formulations

are they interchangeable?

A

non-modified
modified

NOT Interchangeable

49
Q

which cyclosporine formulation has improved bioavailability

A

modified

50
Q

cyclosporine target torugh

A

100-400 ng/ml

51
Q

which drugs raise calcinuerin inhibitor levels

A
verapamil
diltiazem
azoles
erythromycin
clarithromycin
ritonavir
grapefruit
52
Q

which drugs can decrease calcineurin inhibitor levels

A

rifampin/rifabutin
phenytoin/phenobarbital
carbamazepine
st. johns wort

53
Q

cyclosporine AE

A

hypercholesterolemia
hypertriglyceridemia
hypertension
nephrotoxicity

54
Q

tacrolimus AE

A
neurotoxicity
diabetes+hyperglycemia
nephrotoxicity
alopecia
Gi
55
Q

How does CNI PK change in liver dysfunction

A

half life increased

56
Q

how CNI PK change in renal dysfunction

A

no change

57
Q

Azathioprine MOA

A

incorporated into nucleic acids to inhibit RNA and DNA synthesis to inhibit immune cell proliferation

58
Q

Azathioprine drug interactions

A

Allopurinol! Due to affecting xanthine oxidase

Must reduce AZA to one-quarter of the original dose but likely best to avoid all together

59
Q

Mycophenolic acid MOA

A

inhibits the de novo pathway of purine synthesis, which limits progression of activated T and B cells

60
Q

mycophenolic acid AE

A

GI
hematologic and lymphatic
Pregnancy category D

61
Q

Mycophenolic acid types

A

mofetil (IR)

sodium (EC DR)

62
Q

mycophenolic acid interchange

A

therapeutically equivalent and interchangable

mofetil 250mg = sodium 180mg

63
Q

mTOR inhibitors MOA

A

inhibits signal-3 of t-cell activation and ultimately t-cell proliferation

64
Q

what drugs are mTOR inhibitors

A

sirolimus

everolimus

65
Q

sirolimus target trough

A

4-12 ng/ml

66
Q

everolimus target trough

A

goal 12 hour trough is 3-8

67
Q

corticosteroid equivalent dosing

A

20mg H= 5 mg P= 4 mg M= 0.75mg D

68
Q

Belatacept use

A

kidney transplant

69
Q

belatacept MOA

A

Blocks the CD28 mediated costimulation of T lymphocytes by binding to CD80 and CD86 on antigen-presenting cells to be a selective t-cell costimulation blocker