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
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
3
Q
In which situations will they transplant a heart?
A
- Heart Failure
- arrhythmias
- Coronary artery disease
- cardiomyopathies
4
Q
in which situations will they transplant a kidney?
A
-End stage renal disease which can be:
-diabetic
hypertensive
IgA nephropathy
SLE
5
Q
In which condions will they translpant the liver?
A
Cirrhosis:
- alcoholic, Heb B, C
- fulmiantn hepatic failure
- HCC
6
Q
in which situations iwll the transplant a lung?
A
cystic fibraosis
pulmonary fibrosis
COPD
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)
8
Q
timescale of hyperacute rejection?
A
minutes
9
Q
timescale of accelarated rejection?
A
1-5 days
10
Q
timescale of acute humoral rejection?
A
> 1 week
11
Q
timescale of acute cell mediated rejection ?
A
> 2weeks
12
Q
timescale of chronic rejection?
A
months to years
13
Q
what are the two calcineurin inhibitors generic names?
A
tacrolimus
cyclosporine
14
Q
what two coritcosteoroids are used in tranplant patients?
A
methyprednisolone
prednisone
15
Q
what are the antiproliferative agetns used in transplant patients?
A
azathioprine cylophosphamide mycophenolate mofetil (cellcetp) mycophonolic acid (myfortic) sirolimus everolimus
16
Q
everolimus
A
zortress
17
Q
sirolimus
A
rapamune
18
Q
cellcept
A
mycopheonlate mofetyl
19
Q
myfortic
A
mycophenolic acid
20
Q
imuran
A
azathioprine
21
Q
cytoxan
A
cyclophosphamide
22
Q
sandimmune
A
cyclosporine
23
Q
prograf
A
tacrolimus
24
Q
atgam
A
antihymocyte globulin
25
Thymoglubulin
antithymocyte globulin
26
gengraf
cyclosporin
27
solumedrol
methyprednisolone
28
siulect
basilixmab
29
deltasone
prednisone
30
neoral
cyclosporin
31
nulogix
belatecpet
32
what is the MOA of calcineurin inhibitors?
they inhibit calcineurin which is a protein needed for the transcription of the IL2 gene. This leads to t-cell activation and proliferation inhibition.
33
what is the therapeutic range of tacrolimus?
5-15ng/ml
34
what is the therapeutic range for cyclosporine
150-400ng/ml
35
Major Ddi's with calcineurin inhibitors?
CYP3A4 substrates
36
cyclosporine dosing & formulations
25, 50, 100mg capsules, 100mg/50ml oral solution
| 5-10mg/kg/day (typical 100-400mg po BID)
37
what is the advantage of Neoral vs Sandimmune?
absorbed faster and higher AUC
38
what is the balance you play with antirejection medications?
Increased levels othe medicaitons decrease rejection but increase sideffects (immunosupression)
39
Target tacrolimus dose
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
what are the advantages/disadvantages of cyclosporine?
+less hyperglycemia/ N/V than tacrolimus
- hypertension, hyperlipidemia than tacrolimus
- Gingival hyperplasia, hirsuitism
- neurotoxicity, nephrotoxicity
41
what are the advantages/disadvantages of Tacrolimus?
+less overall SE compared to cyclosporine
+less HTN, HLD > cyclo
+No hirsutism or gingival hyperpalsia
-hyperlipidemia, N/V > cyclo
42
Which agents will increase / dec cyclosporine and tacrolimus concentrations?
Cyp3A4 Inhibitors inc levels,
CYP3A4 inducers decrease levels
Aminoglycosides, Amphotericin B, NSAIDS potentiate nephrotoxic effects
43
what is the mechanism of action of Corticosteroids as an immunosupressant for transplants?
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
Corticosteroid side effects:
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
MOA of azathioprine
chemical analog of purines that inhits RNA and DNA synthesis, therefroe blocks proliferation of B and T lymphocytes
46
immunosupressant dose of azathioprine?
1-2mg/kg/day
47
main drug interaciton with azathioprine
allopurinol (must dec dose by 75% of aza)
| Ace inhibitors: sever leukopenia
48
adverse effects of azathiprine
myelosuppression** dose related (leukopenia, thrombocytopenia)
alopecia
hepatotoxicity usually w/in 6 mon of transplantation (potential)
malignancy
49
what is the MOA of myecophenolate?
gets covnverted to mycophenolic acid (active) then inhibits de novo purine biosynthesis by inhibiting IMP dehydrogenase
50
what is the dosing for CellCept (MMF)
1-1.5gm PO/IV BID
51
IV to PO coversion for CellCept?
1:1
52
What are the AE for Mycophenolate mofetil?
GI* : N/V/D/Abd pain, gastritis, GI hemorrage
Hematologic**leukopenia, thrombocytopenia
lymphoma, melanoma, CMV, HSV
53
What is the conversion factor between Enteric coted Mycophenolic acid and mycophenolate?
720mg EC-MPS : 1000mg MMF
54
what is sirolimus previous name?
Rapamycin
55
What is the MOA of Sirolimus and Everolimus?
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
what is the dosage of sirolimus for transplant?
2-5mg po daily
| monitor levels
57
what is the dosing for everolimus for translpant
0.75mg po bid
| monitor levels
58
what are some disadavantages of the antiporliverative agents versus Azathioprine and mycophenolate?
have more anemia and more hypertriglyceridemia, and hypercholesterolemia
59
what are antithymocyte globulins?
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
which brand is made in horses?
Atgam
61
which brand is made in rabbits?
Thymoglobulin
62
what are the adverse effects of antithymocytes?
```
fevers, chills , rigors
leuokpenia, thormbocytopenia
infections
serum skincess
anaphylaxis
malignancies
```
63
what is the induction dosing of antithymocytes?
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
Treatment of rejection doses?
Atgam 10-30mg/kg/day IV QD x 7-14 days
| Thymoglobulin 1.5mg/kg/day IV QD x 7-14 days
65
what is the mechanism of action of basiliximab?
it is an antibody that is IL-2 receptor antagonist. It stopes IL2 from activating T lymphocytes
66
indication of basiliximab?
used for acute rejection in renal transplant and should be used with cyclosporine and corticosteroids
67
what is the MOA of belatacept?
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
what is the indication of belatacept?
prevent rejection in kidney transplant pts, Requires, basiliximab induciton_+ belatacept+ MMF + corticosteroids
69
dosing belatacept?
day 1 and day 5: 10mg/kg IV
end of week 2, 4, 8, 12 10mg/IV
Maintenance q 4 weeks 5mg/kg
70
what adverse effects of beltacept?
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
what is the typical triple regimen for transplants require?
corticosteroid taper
calcineurin inhibitor
antiproliferative agent
72
what is the balance in immunosupressive regimens?
rejection VS side effects, infections, malignancies
73
what are major complications after transplant?
```
bone marrow suppression
hyperglycemai
hyperlipdemia
hyperkalemia
hypertendion
hyperlipidemia
infections
malignancies
ostoeprosis
renal dysfunction
recurrence of disease
cosmetic changes
GI SEs
financial impact
```
74
define HTN in transplant patients?
BP > 140/90 or use of antihypertensive drugs
75
which transplant drugs can cause HTN?
Calcineurin inhibitors
| Corticosteroids. None of the rest
76
what is your target blood pressure?
<130/80 accorting to JNC 7 , NKF, KDIGO
77
which agents are good for HTN in translpant?
CCB
| BB
78
which ones are not good choices?
ACE
ARBs
cuz decrease renal bood flow, GFR, inc SCr , hyperkalemia
Diuretics: hyperlidemia, hyperglycemia, electrolyte changes
79
how can you modify the current immunosupressant regimen?
cyclosprine withdrawal
alternate day prednisone
steroid avoidance
(NOT COMMONLY DONE)
80
which drug agents can cuase hyperlipdemai?
```
corticosteroids
cyclosporine
sirolimus/everolimus
diuretcis
antihypertensives
```
81
what is the target LDL for post transplant?
< 100mg/dL
82
changing immunosuppressive regimen to dec HLD?
change from cyclospirne to tac
avoid sirolimus
w/d corticosteroid
give anti HLD agent
83
what is the DOC for HLD?
Statins: atorvastatin or pravastatin to avoid DDIs
| use lower doses, avoid use with gemfibrozil
84
why are bile acid resins a bad idea for post transplant?
dec absorption of fat soluble vitamins
hypertriglyceridemia
dec CSA absorption
