Solid Organ Transplant Dr. Covert EXAM 3 Flashcards
What are the potent and less potent Induction agents that are used to reduce the number of immune cells for organ transplants?
REMINDER
potent: T-cell depleting agents
-Thymoglobulin, Alemtuzumab (Campath)
less potent: Non-T-cell depleting agents
-Basalixumab (Simulect) - IL-2 inhibitor
-high dose steroids
What are the drugs that are used for maintenance immunosuppression after organ transplantation?
REMINDER
-Calcineurin inhibitors
Tacrolimus, Cyclosporine
-Antiproliferatives
Mycophenolate, Azathioprine
-mTOR inhibitors
Sirolimus, Everolimus
-T-Cell Co-Stimulation Blocker
Belatacept
-low dose steroids
What is the purpose of Induction therapy?
- potent and rapid immunosuppression
- Delay the initiation of maintenance therapy
What are the factors that measure the risk for organ rejection (immunologic risk)?
-cPRA (calculated panel reactive antibody): the higher the percent, the more likely the rejection
-HLA mismatch
-prior immunologic mismatch (blood transfusion, pregnancies)
-living vs deceased donor
-potency of immunosuppressants
What are the risk factors for infections in organ transplants?
-Comorbid Conditions (drugs, chemo, immunosuppressive state, HIV)
-Donor/ Recipient (what bacteria did the donor have)
-Serostatus (prior cytomegalovirus exposure, risk is low if recipient and donor don’t have CMV antibodies or both positive)
How potent does an immunosuppressant need to be for a patient with low immunologic risk?
young, with no dialysis or blood transfusion, and male, with a living-related donor transplant.
low potent immunosuppressant for induction
-Basalixumab (IL-2)
if the risk is high go with T-cell-depleting agents, otherwise the organ will be rejected
What would you monitor for a patient on Antithymocyte globulin (Thymoglobulin)?
(potent immunosuppressor)
-CBC (thrombocytopenia, neutropenia)
-ADE: infections, malignancies
What is the goal trough level for Tacrolimus after 12 hours?
!!!
6-12 ng/ml
Know how to adjust dosing based on the goal trough!!!
What is the goal trough level after 12 hours and the goal C2 level for Cyclosporine?
C2 trough (2h after the dose): >1000 ng/mL
12h trough: 125-275 ng/mL
What is the IV to PO conversion for Tacrolismus?
A patient was started on Tacrolimus PO 6mg q12.
What is the equivalent IV dose?
!!!
NAPLEX
1:4
IV:PO
3 mg IV
a dose error has significant side effects, especially when changing to IV (higher peak concentration)
What is the IV to PO conversion for Cyclosporine?
!!!!
NAPLEX
1:3
IV:PO
What are the common DDI with Calcineurin inhibitors?
-CYP3A4 inhibitor/inducer !!!
-> recognize CYP3A4 inh and inducer !!!
-NSAIDs cause afferent vasoconstriction
-ACEi/ARB cause efferent vasodilation (just like calcineurin inhibitors)
-> causes AKI
this is not a DDI actually:
-Bilirubin (reduced biliary clearance of calcineurin inhibitors when Bilirubin is high (hepatic dysfunction))
How long does it take for the CYP induction to have an effect?
How long for CYP inhibition?
CYP induction has a slow onset and offset (2-3 weeks)
-> relies on the half-life of the CYP enzymes, not the drug that causes the CYP induction
CYP inhibition has a fast onset and fast offset
->relies on the half-life of the drug causing the inhibition, example: Diltiazem has a short-halflife, so the DDI will last for a short time, Amiodarone has a long half-life -> long duration of CYP inhibition
Tacrolimus is eliminated by which proteins?
How does diarrhea affect Tacrolimus levels?
!!!
P-glycoprotein (ATP efflux pump)
moves the drug from the body into the gut
P-glycoprotein is eliminated in the stool in patients with diarrhea
-> Tacrolimus levels go up
What are the side effects in a patient with elevated Tacrolismus levels?
-renal impairment (afferent arterial vasoconstriction, like NSAIDs) !!!
-infections
-electrolyte abnormalities
-new-onset diabetes, HTN, hyperlipidemia
-Neurotoxicity (tremor, seizures)
Which drug class has a DDI with Cyclosporin?
Statins
except Pravastatin
What is a common side effect of Mycophenolate?
diarrhea !!
also:
-teratogenicity
-reduced WBC, platelets
MOA: inhibits lymphocyte proliferation
What might help for a patient on Mycophenolate who complains about diarrhea?
What is the equivalent dose of Cellceptic for Myfortic?
!!!
might change to Myfortic (another brand) which has less diarrhea in some patients
720 mg Myfortic = 1000 mg CellCeptic
IV:PO for CellCeptic is 1:1
Which drug has a DDI with Azathioprine?
Allopurinol
increases Azathioprine levels
(also seen with 6-MP)
What are mTOR inhibitors? Don’t confuse with calcineurin inhibitors.
What is the MOA?
Sirolimus, Everolimus
MOA: prevent T-cell proliferation
What are the side effects of mTOR inhibitors?
-Impaired wound healing !!!
-hypertriglyceridemia
-hyperlipidemia
-decrease in WBC and platelets
-peripheral edema
-proteinuria
-oral ulcers
Which drug inhibits signal 2 of immune cell activation?
Belatacept (Nulojix)
-Binds CD80 and CD86 receptors on APCs and blocks the interaction to T-cells
Belatacept is only used for the transplantation of which organ?
What test is required before the procedure?
!!!
Kidney transplantation
patients have to be EBV seropositive!!! (so have been exposed to EBV)
What is a side effect of Belatacept in EBV-negative patients?
!!!
posttransplant lymphoproliferative (PTLD)
type of lymphoma
A patient was started on Tacrolimus 3mg BID, but his level was too low at 5 ng/ml.
What should his regimen be twice daily to result in levels of 10-12?
EXAM !!!
6-7 mg BID
(kinetics are linear, doubling of the dose results in doubling of serum levels)
What is the number cause of death in transplant patients?
CVD
What is the goal BP for transplant patients?
What is the preferred antihypertensive drug?
Goal BP: <130/80
-DHB-CCB
-ACEi/ARBs later: should be avoided for 1 year due to interaction with calcineurin inhibitors)
BB/diuretics if indicated
Which immunosuppressive drug should be avoided in patients with hyperlipidemia?
mTOR
-it causes hyperlipidemia and increases TG
-Caution: DDI between Cyclosporin and statins
Which drugs can cause New-Onset diabetes after transplant (NODAT)?
-Steroids: Insulin resistance
-CNIs (Tacrolimus > Cyclosporine): β-cell toxicity
-mTORinhibitors: β-cell toxicity and insulin resistance
BG levels fluctuate in the first month, so it takes 1 month to tell if they have NODAT
What are ways to avoid malignancies after transplantations?
-Appropriate Immunosuppressive selection and dosing !!!
- Reduction of immunosuppression
-Avoidance of azathioprine (if possible), mycophenolate is the Antiproliferative with less risk for cancer
-Switch to mTOR inhibitor
-use sunscreen (skin cancer)
-patients have to be on remission of cancer before getting a transplant (Chemotherapy)
