Solid Organ Transplant Flashcards
When they remove a kidney do they take the old kidney off?
usually they leave the old bad kidney and put in a new one in a different location
when they transplant a liver do they take the old one out?
yes they remove the old one an put in a new one
In which situations will they transplant a heart?
- Heart Failure
- arrhythmias
- Coronary artery disease
- cardiomyopathies
in which situations will they transplant a kidney?
-End stage renal disease which can be:
-diabetic
hypertensive
IgA nephropathy
SLE
In which condions will they translpant the liver?
Cirrhosis:
- alcoholic, Heb B, C
- fulmiantn hepatic failure
- HCC
in which situations iwll the transplant a lung?
cystic fibraosis
pulmonary fibrosis
COPD
what are the contraindications for a transplant?
- 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)
timescale of hyperacute rejection?
minutes
timescale of accelarated rejection?
1-5 days
timescale of acute humoral rejection?
> 1 week
timescale of acute cell mediated rejection ?
> 2weeks
timescale of chronic rejection?
months to years
what are the two calcineurin inhibitors generic names?
tacrolimus
cyclosporine
what two coritcosteoroids are used in tranplant patients?
methyprednisolone
prednisone
what are the antiproliferative agetns used in transplant patients?
azathioprine cylophosphamide mycophenolate mofetil (cellcetp) mycophonolic acid (myfortic) sirolimus everolimus
everolimus
zortress
sirolimus
rapamune
cellcept
mycopheonlate mofetyl
myfortic
mycophenolic acid
imuran
azathioprine
cytoxan
cyclophosphamide
sandimmune
cyclosporine
prograf
tacrolimus
atgam
antihymocyte globulin
Thymoglubulin
antithymocyte globulin
gengraf
cyclosporin
solumedrol
methyprednisolone
siulect
basilixmab
deltasone
prednisone
neoral
cyclosporin
nulogix
belatecpet
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.
what is the therapeutic range of tacrolimus?
5-15ng/ml
what is the therapeutic range for cyclosporine
150-400ng/ml
Major Ddi’s with calcineurin inhibitors?
CYP3A4 substrates
cyclosporine dosing & formulations
25, 50, 100mg capsules, 100mg/50ml oral solution
5-10mg/kg/day (typical 100-400mg po BID)
what is the advantage of Neoral vs Sandimmune?
absorbed faster and higher AUC
what is the balance you play with antirejection medications?
Increased levels othe medicaitons decrease rejection but increase sideffects (immunosupression)
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
what are the advantages/disadvantages of cyclosporine?
+less hyperglycemia/ N/V than tacrolimus
- hypertension, hyperlipidemia than tacrolimus
- Gingival hyperplasia, hirsuitism
- neurotoxicity, nephrotoxicity
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
Which agents will increase / dec cyclosporine and tacrolimus concentrations?
Cyp3A4 Inhibitors inc levels,
CYP3A4 inducers decrease levels
Aminoglycosides, Amphotericin B, NSAIDS potentiate nephrotoxic effects
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
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
MOA of azathioprine
chemical analog of purines that inhits RNA and DNA synthesis, therefroe blocks proliferation of B and T lymphocytes
immunosupressant dose of azathioprine?
1-2mg/kg/day
main drug interaciton with azathioprine
allopurinol (must dec dose by 75% of aza)
Ace inhibitors: sever leukopenia
adverse effects of azathiprine
myelosuppression** dose related (leukopenia, thrombocytopenia)
alopecia
hepatotoxicity usually w/in 6 mon of transplantation (potential)
malignancy
what is the MOA of myecophenolate?
gets covnverted to mycophenolic acid (active) then inhibits de novo purine biosynthesis by inhibiting IMP dehydrogenase
what is the dosing for CellCept (MMF)
1-1.5gm PO/IV BID
IV to PO coversion for CellCept?
1:1
What are the AE for Mycophenolate mofetil?
GI* : N/V/D/Abd pain, gastritis, GI hemorrage
Hematologic**leukopenia, thrombocytopenia
lymphoma, melanoma, CMV, HSV
What is the conversion factor between Enteric coted Mycophenolic acid and mycophenolate?
720mg EC-MPS : 1000mg MMF
what is sirolimus previous name?
Rapamycin
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.
what is the dosage of sirolimus for transplant?
2-5mg po daily
monitor levels
what is the dosing for everolimus for translpant
0.75mg po bid
monitor levels
what are some disadavantages of the antiporliverative agents versus Azathioprine and mycophenolate?
have more anemia and more hypertriglyceridemia, and hypercholesterolemia
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
which brand is made in horses?
Atgam
which brand is made in rabbits?
Thymoglobulin
what are the adverse effects of antithymocytes?
fevers, chills , rigors leuokpenia, thormbocytopenia infections serum skincess anaphylaxis malignancies
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
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
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
indication of basiliximab?
used for acute rejection in renal transplant and should be used with cyclosporine and corticosteroids
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
what is the indication of belatacept?
prevent rejection in kidney transplant pts, Requires, basiliximab induciton_+ belatacept+ MMF + corticosteroids
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
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
what is the typical triple regimen for transplants require?
corticosteroid taper
calcineurin inhibitor
antiproliferative agent
what is the balance in immunosupressive regimens?
rejection VS side effects, infections, malignancies
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
define HTN in transplant patients?
BP > 140/90 or use of antihypertensive drugs
which transplant drugs can cause HTN?
Calcineurin inhibitors
Corticosteroids. None of the rest
what is your target blood pressure?
<130/80 accorting to JNC 7 , NKF, KDIGO
which agents are good for HTN in translpant?
CCB
BB
which ones are not good choices?
ACE
ARBs
cuz decrease renal bood flow, GFR, inc SCr , hyperkalemia
Diuretics: hyperlidemia, hyperglycemia, electrolyte changes
how can you modify the current immunosupressant regimen?
cyclosprine withdrawal
alternate day prednisone
steroid avoidance
(NOT COMMONLY DONE)
which drug agents can cuase hyperlipdemai?
corticosteroids cyclosporine sirolimus/everolimus diuretcis antihypertensives
what is the target LDL for post transplant?
< 100mg/dL
changing immunosuppressive regimen to dec HLD?
change from cyclospirne to tac
avoid sirolimus
w/d corticosteroid
give anti HLD agent
what is the DOC for HLD?
Statins: atorvastatin or pravastatin to avoid DDIs
use lower doses, avoid use with gemfibrozil
why are bile acid resins a bad idea for post transplant?
dec absorption of fat soluble vitamins
hypertriglyceridemia
dec CSA absorption
