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Therapeutics > Solid Organ Transplant > Flashcards

Solid Organ Transplant Flashcards

1
Q

When they remove a kidney do they take the old kidney off?

A

usually they leave the old bad kidney and put in a new one in a different location

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2
Q

when they transplant a liver do they take the old one out?

A

yes they remove the old one an put in a new one

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3
Q

In which situations will they transplant a heart?

A
  • Heart Failure
  • arrhythmias
  • Coronary artery disease
  • cardiomyopathies
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4
Q

in which situations will they transplant a kidney?

A

-End stage renal disease which can be:
-diabetic
hypertensive
IgA nephropathy
SLE

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5
Q

In which condions will they translpant the liver?

A

Cirrhosis:

  • alcoholic, Heb B, C
  • fulmiantn hepatic failure
  • HCC
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6
Q

in which situations iwll the transplant a lung?

A

cystic fibraosis
pulmonary fibrosis
COPD

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7
Q

what are the contraindications for a transplant?

A
  • Active infection
  • significant cardiac disease
  • End stage organ failure (depend on organ)
  • malignancy & risk of metastasis
  • current substance abuse inc eton
  • active smoking
  • noncompliance to meds
  • no financial/social support
  • HIV + (relative, depends)
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8
Q

timescale of hyperacute rejection?

A

minutes

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9
Q

timescale of accelarated rejection?

A

1-5 days

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10
Q

timescale of acute humoral rejection?

A

> 1 week

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11
Q

timescale of acute cell mediated rejection ?

A

> 2weeks

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12
Q

timescale of chronic rejection?

A

months to years

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13
Q

what are the two calcineurin inhibitors generic names?

A

tacrolimus

cyclosporine

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14
Q

what two coritcosteoroids are used in tranplant patients?

A

methyprednisolone

prednisone

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15
Q

what are the antiproliferative agetns used in transplant patients?

A 
azathioprine
cylophosphamide
mycophenolate mofetil (cellcetp)
mycophonolic acid (myfortic)
sirolimus
everolimus
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16
Q

everolimus

A

zortress

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17
Q

sirolimus

A

rapamune

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18
Q

cellcept

A

mycopheonlate mofetyl

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19
Q

myfortic

A

mycophenolic acid

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20
Q

imuran

A

azathioprine

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21
Q

cytoxan

A

cyclophosphamide

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22
Q

sandimmune

A

cyclosporine

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23
Q

prograf

A

tacrolimus

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24
Q

atgam

A

antihymocyte globulin

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25
Q

Thymoglubulin

A

antithymocyte globulin

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26
Q

gengraf

A

cyclosporin

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27
Q

solumedrol

A

methyprednisolone

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28
Q

siulect

A

basilixmab

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29
Q

deltasone

A

prednisone

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30
Q

neoral

A

cyclosporin

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31
Q

nulogix

A

belatecpet

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32
Q

what is the MOA of calcineurin inhibitors?

A

they inhibit calcineurin which is a protein needed for the transcription of the IL2 gene. This leads to t-cell activation and proliferation inhibition.

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33
Q

what is the therapeutic range of tacrolimus?

A

5-15ng/ml

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34
Q

what is the therapeutic range for cyclosporine

A

150-400ng/ml

35
Q

Major Ddi’s with calcineurin inhibitors?

A

CYP3A4 substrates

36
Q

cyclosporine dosing & formulations

A

25, 50, 100mg capsules, 100mg/50ml oral solution

5-10mg/kg/day (typical 100-400mg po BID)

37
Q

what is the advantage of Neoral vs Sandimmune?

A

absorbed faster and higher AUC

38
Q

what is the balance you play with antirejection medications?

A

Increased levels othe medicaitons decrease rejection but increase sideffects (immunosupression)

39
Q

Target tacrolimus dose

A

0.15-0.3mg/kg/day divided q12h (target dose)
typical dose 1-6mg po bid (start at lowest dose then inc to target)
continuous infusion 0.05-0.1mg/kg/day

40
Q

what are the advantages/disadvantages of cyclosporine?

A

+less hyperglycemia/ N/V than tacrolimus

  • hypertension, hyperlipidemia than tacrolimus
  • Gingival hyperplasia, hirsuitism
  • neurotoxicity, nephrotoxicity
41
Q

what are the advantages/disadvantages of Tacrolimus?

A

+less overall SE compared to cyclosporine
+less HTN, HLD > cyclo
+No hirsutism or gingival hyperpalsia
-hyperlipidemia, N/V > cyclo

42
Q

Which agents will increase / dec cyclosporine and tacrolimus concentrations?

A

Cyp3A4 Inhibitors inc levels,
CYP3A4 inducers decrease levels
Aminoglycosides, Amphotericin B, NSAIDS potentiate nephrotoxic effects

43
Q

what is the mechanism of action of Corticosteroids as an immunosupressant for transplants?

A

blocks phosphodiesterase, -> inc cAMP.._ inhbition of of lymphocyte activation

  • decrease in circulating T lymphocytes, inc in circulating neutrophils
  • inhibit IL1/IL2 secrtion
  • inhibit arachidonic acid release
  • suppress macrophage phagocytosis
44
Q

Corticosteroid side effects:

A

Neuro:
Euphoria, psychosis, insomnia

Metabolic:
Hyperglycemia, hyperlipidemia, increased appetite, weight gain, sodium/water rendition, protein catabolism

Cardio: hypertension

Muscle: myopathy, osteoporosis, avascular necrosis

Cosmetic: acne, hirsutisum, moon face, buffallo numb, thin skin, impaired wound healing, peptic ulcer

45
Q

MOA of azathioprine

A

chemical analog of purines that inhits RNA and DNA synthesis, therefroe blocks proliferation of B and T lymphocytes

46
Q

immunosupressant dose of azathioprine?

A

1-2mg/kg/day

47
Q

main drug interaciton with azathioprine

A

allopurinol (must dec dose by 75% of aza)

Ace inhibitors: sever leukopenia

48
Q

adverse effects of azathiprine

A

myelosuppression** dose related (leukopenia, thrombocytopenia)
alopecia
hepatotoxicity usually w/in 6 mon of transplantation (potential)
malignancy

49
Q

what is the MOA of myecophenolate?

A

gets covnverted to mycophenolic acid (active) then inhibits de novo purine biosynthesis by inhibiting IMP dehydrogenase

50
Q

what is the dosing for CellCept (MMF)

A

1-1.5gm PO/IV BID

51
Q

IV to PO coversion for CellCept?

A

1:1

52
Q

What are the AE for Mycophenolate mofetil?

A

GI* : N/V/D/Abd pain, gastritis, GI hemorrage
Hematologic**leukopenia, thrombocytopenia
lymphoma, melanoma, CMV, HSV

53
Q

What is the conversion factor between Enteric coted Mycophenolic acid and mycophenolate?

A

720mg EC-MPS : 1000mg MMF

54
Q

what is sirolimus previous name?

A

Rapamycin

55
Q

What is the MOA of Sirolimus and Everolimus?

A

inhibitors of MTOR which eventually inhibtis phosphorialtion of a kinase which blocks IL2 signal strnasuction. Stops Cells from progressing from G1 to S phase.

56
Q

what is the dosage of sirolimus for transplant?

A

2-5mg po daily

monitor levels

57
Q

what is the dosing for everolimus for translpant

A

0.75mg po bid

monitor levels

58
Q

what are some disadavantages of the antiporliverative agents versus Azathioprine and mycophenolate?

A

have more anemia and more hypertriglyceridemia, and hypercholesterolemia

59
Q

what are antithymocyte globulins?

A

they are antibodies produced by horses or rabits agains human thymocytes. They are antibodies agains human T cell antigens. This leads to decrease in t cell circulation

60
Q

which brand is made in horses?

A

Atgam

61
Q

which brand is made in rabbits?

A

Thymoglobulin

62
Q

what are the adverse effects of antithymocytes?

A 
fevers, chills , rigors
leuokpenia, thormbocytopenia
infections
serum skincess
anaphylaxis
malignancies
63
Q

what is the induction dosing of antithymocytes?

A

Atgam 10-30mg/kg/day IV QD x 7-14 days, first dose withing 24 h after transplant
Thymoglobulin 1.5mg/kg/day IV QD x 7-14 days (to ~ 6mg/kg/course) first dose withing 24 h of transplantation

64
Q

Treatment of rejection doses?

A

Atgam 10-30mg/kg/day IV QD x 7-14 days

Thymoglobulin 1.5mg/kg/day IV QD x 7-14 days

65
Q

what is the mechanism of action of basiliximab?

A

it is an antibody that is IL-2 receptor antagonist. It stopes IL2 from activating T lymphocytes

66
Q

indication of basiliximab?

A

used for acute rejection in renal transplant and should be used with cyclosporine and corticosteroids

67
Q

what is the MOA of belatacept?

A

blocks interactions of APC’s and T Cells so that T cells dont get activated
Also, by blocking this interaction it leads to anergy and induces apoptosis of T cells

68
Q

what is the indication of belatacept?

A

prevent rejection in kidney transplant pts, Requires, basiliximab induciton_+ belatacept+ MMF + corticosteroids

69
Q

dosing belatacept?

A

day 1 and day 5: 10mg/kg IV
end of week 2, 4, 8, 12 10mg/IV
Maintenance q 4 weeks 5mg/kg

70
Q

what adverse effects of beltacept?

A

increased risk of PTLD (lymphoma) esp with higher does
contraindicated in EBV seronegative patients because of a higher risk of developing PTLD
Risk of PML
hypotension
hypokalemia
arthralgia
reactivate TB

71
Q

what is the typical triple regimen for transplants require?

A

corticosteroid taper
calcineurin inhibitor
antiproliferative agent

72
Q

what is the balance in immunosupressive regimens?

A

rejection VS side effects, infections, malignancies

73
Q

what are major complications after transplant?

A 
bone marrow suppression
hyperglycemai
hyperlipdemia
hyperkalemia
hypertendion
hyperlipidemia
infections
malignancies
ostoeprosis
renal dysfunction
recurrence of disease
cosmetic changes 
GI SEs
financial impact
74
Q

define HTN in transplant patients?

A

BP > 140/90 or use of antihypertensive drugs

75
Q

which transplant drugs can cause HTN?

A

Calcineurin inhibitors

Corticosteroids. None of the rest

76
Q

what is your target blood pressure?

A

<130/80 accorting to JNC 7 , NKF, KDIGO

77
Q

which agents are good for HTN in translpant?

A

CCB

BB

78
Q

which ones are not good choices?

A

ACE
ARBs
cuz decrease renal bood flow, GFR, inc SCr , hyperkalemia
Diuretics: hyperlidemia, hyperglycemia, electrolyte changes

79
Q

how can you modify the current immunosupressant regimen?

A

cyclosprine withdrawal
alternate day prednisone
steroid avoidance
(NOT COMMONLY DONE)

80
Q

which drug agents can cuase hyperlipdemai?

A 
corticosteroids
cyclosporine
sirolimus/everolimus
diuretcis
antihypertensives
81
Q

what is the target LDL for post transplant?

A

< 100mg/dL

82
Q

changing immunosuppressive regimen to dec HLD?

A

change from cyclospirne to tac
avoid sirolimus
w/d corticosteroid
give anti HLD agent

83
Q

what is the DOC for HLD?

A

Statins: atorvastatin or pravastatin to avoid DDIs

use lower doses, avoid use with gemfibrozil

84
Q

why are bile acid resins a bad idea for post transplant?

A

dec absorption of fat soluble vitamins
hypertriglyceridemia
dec CSA absorption

Therapeutics (23 decks)

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