Transplant Flashcards
People with which type of blood are considered universal donors?
Type O
but can only receive type O blood
People with Type A blood will react against what types of blood?
Type B and Type AB
People with Type B blood will react against what types of blood?
Type A, Type AB
Prior to any transplant, tissue typing or crossmatching is performed to assess donor-receipt compatibility for _______ and ________
human leukocyte antigen (HLA) and ABO blood group
a mismatch would lead to acute rejection
An _____ is the transplant of an organ or tissue from one individual to another of the same species with a different genotype
allograft; can also be called an allogenic transplant or homograft
A transplanted organ from a genetically identical donor (such as a twin) is called an ____
isograft
A transplant in the same patient from one site to another
autograft - termed autologous transplant
Induction immunosuppression is given BEFORE or at the time of transplant to …
prevent acute rejection during the early post-transplant period
What does induction immunosuppression consist of?
a short course of effective IV medication, either a biological drug or monoclonal antibody sometimes combined with high dose IV steroids
What is the most commonly used induction drug?
an interleukin2 receptor antagonist - basiliximab
expressed on activated t-lymphocytes and is a critical pathway for activating t lymphocytes to attack and reject the organ
ONLY used for prevention
Patients at a higher risk of rejection can receive…
antithymocyte globulin
these drugs are made by injecting human T lymphocytes into animals and then back to humans
*used for both induction and treatment of rejection
This drug is off-label but can be used for induction
alemtuzumab
Induction immunosuppression is not required if the transplant is from…
an identical twin
Brand: Atgam - equine
Brand: Thymoglobulin - rabbit
Generic: antithymocyte Globulin
This drug has a boxed warning for anaphylaxis
antithymocyte Globulin
*premedicate (Benadryl, Tylenol, steroids) to lessen infusion-related reactions
Brand: Simulect
Generic: basiliximab (IL2 receptor antagonist)
well tolerated
Maintenance immunosuppression is generally provided by the combination of:
a calcineurin inhibitor (CNI) +
an anti proliferative agent +/-
Steroids
Why do we use multiple mechanisms through different drug classes?
to both lower toxicity risk of the individual immunosuppressants and to reduce the risk of graft rejection
Systemic steroids used
Prednisone typically
What drug?
short-term effects include: fluid retention, stomach upset, emotional instability, insomnia, inc appetite, weight gain, acute rib ein blood glucose, and blood pressure
Long term side effects: adrenal suppression/cushing’s, impaired wound healing, inc BP, DM, acne, osteoporosis, impaired growth in children
prednisone
These drugs inhibit t lymphocyte proliferation by altering purine synthesis
anti proliferative agents
What types of drugs are mycophenolate mofetil, and mycophenolic acid, and azathioprine?
anti proliferative agents
S/e: diarrhea, GI upset
NOT INTERCHANGEABLE
Brand: CellCept
generic: mycophenolate mofetil
Brand: Myfortic
Generic: mycophenolic acid
What is the boxed warning for mycophenolate mofetil, and mycophenolic acid?
inc risk of infection, inc development of lymphoma and skin malignancies, inc risk of congenital malformations and spontaneous abortions
mycophenolate mofetil, and mycophenolic acid - which is enteric coated to decrease diarrhea?
mycophenolic acid
mycophenolate mofetil, and mycophenolic acid - which is stable in D5W only?
mycophenolate mofetil
*these drugs decrease oral contraceptives!
Brand: Azasan, Imuran
generic: azathioprine
This drug has warnings for patients with genetic deficiency of thipurine methyltransferase (TPMT_ are at high risk for myleosuppression
azathioprine
This drug works by suppressing cellular immunity by inhibiting T lymphocyte activation
calcineurin inhibitors
What is an example of a calcineurin inhibitor?
tacrolimus, cyclosporine
Brand: Prograf
generic: tacrolimus
This drug has a boxed warning for increase susceptibility to infection, lymphoma
s/e: inc BP, nephrotoxicity, inc BG, neurotoxicity, hyperkalemia, hyperlipidemia, QT Prolongation
tacrolimus
numerous drug interactions too!!! CYP450 3A4 and P-gp substrate
What labs need to be monitored with tacrolimus?
trough levels
serum electrolytes: K, Phos, Mg; renal function, LFTs, BP, BG, lipid profile
Can you interchange XL to IR for tacrolimus?
NO!
Tacrlimus - IV is administered as a continuous infusion in a what container?
non-PVC
Brand: Gengraf, Neoral (modified); Sandimmune (non-modified)
generic: cyclosporine
This drug has boxed warnings for: renal impairment, inc risk of lymphoma, skin cancer, inc risk of infection, inc BP
cyclosporine
can the non-modified be interchanged with the modified?
NO! modified has 20-50% greater bioavailability compared to non-modified
This drug’s side effect profile: inc BP, nephropathy, hyperkalemia, hypo magnesia, hirsutism, gingival hyperplasia, edema, inc BG, neurotoxicity, QT Prolongation
cyclosporine
What labs need to be monitored with cyclosporine?
trough levels, serum electrolytes (K, Mg), renal function, BP, BG, lipid profile
What drug can you not administer from a plastic or styrofoam cup?
cyclosporine
What drops can be used for dry eyes?
Restasis
This drug class inhibit T lymphocyte activation and proliferation, may be synergistic with CNIs
mammalian target of rapamycin (mTOR) kinase inhibitors
Everolimus
Sirolimus
are examples of what drug class?
mTOR kinase inhibitors
This mTOR drug can cause peripheral edema, inc BP, and should not be used within 30 days of transplant
everolimus
many D/I – 3A4 substrate
Brand: Zortress
generic: everolimus
Brand: Rapamune
generic: sirolimus
This mTOR drug has warnings for impaired wound healing, hyperlipidemia and side effects are extensive:
irreversible pneumonitis, bronchitis, cough (d/e therapy If this develops), inc BG, peripheral edema
sirolimus
D/I – 3A4 substrate
Sirolimus - are tablets and oral solution bioequivalent?
no!!!
This drug binds to CD80 and CD86 to block T cell costimulation and production of inflammatory mediators
belatacept
Brand: Nulojix
generic: belatacept
This drug has a boxed warning for increase risk of post-transplant lymphoproliferative disorder (PTLD); use in EBV seropositive patients ONLY
belatacept
What patients do you use belatacept in?
Those that are EBV seropositive!!!
This drug has an inc risk of OI, sepsis, and or fatal infection, inc risk of TB… test for latent TB prior to initiation and TREAT latent TB prior to use
belatacept
What are options for induction immunosuppressants?
- basiliximab
- antithymocyte globulin in patients at higher risk of rejection
- maintenance drugs at higher doses
What are maintenance immunosuppressants?
- CNIs – tacrlimus > cyclosporine
- adjuvant medications given with a CNI
- anti proliferative agents (mycophenolate or azathioprine)
- mTOR inhibitors (everolimus or sirolimus)
- belatacept - steroids
Azathioprine is metabolized by xanthine oxidase. Avoid with which drugs?
allopurinol or febuxostat
Which drug can dec OC?
mycophenolate
Avoid grapefruit juice and st john’s wort with either…
CNI
Caution with additive drugs that are nephrotoxic with
tacrolimus and cyclosporine
Caution with additive drugs that raise blood glucose with
tacrolimus
steroids
cyclosporine
mTOR inhibitors
Caution with additive drugs that worsen lipids with
mTOR inhibitors
steroids
cyclosporine
caution with additive drugs that raise bP with
steroids
cyclosporine
tacrolimus
What are the three monitoring questions?
Is it a sx of drug toxicity, organ rejection, or infection?
What are the common symptoms of acute rejection?
flu-like symptoms (chills, body aches, nausea, cough, SOB) & organ specific symptoms
Which maintenance immunosuppressants have the highest incidence of: nephrotoxicity
tacrolimus and cyclosporine
Which maintenance immunosuppressants have the highest incidence of: worsening or new diabetes
tacrolimus, steroids, and cyclosporine
Which maintenance immunosuppressants have the highest incidence of: worsening lipid parameters
mTOR inhibitors, steroids, cyclosporine
Which maintenance immunosuppressants have the highest incidence of: hypertension
steroids, cyclosporine, and tacrolimus
ALL transplant recipients must self monitor for symptoms of
infection!
Fever of 100.5/38C or higher, chills
cough, more sputum or change in color of sputum, sore throat
pain with passing urine ear or sinus pain
mouth sores or a wound that does not heal
Acute rejection of the transplanted organ arises from either
T cells (cellular) or B cell (humoral or antibody) mediated mechanisms
both can occur simulataneously !! biopsy needs to be done
What is the initial approach to acute rejection?
high-dose steroids
For _____ rejection, the steroids and increased levels of maintenance immunosuppression are adequate to treat the rejection
cellular
[[[humoral rejection is way more complicated… need to remove antibodies and administer IVIG]]]
For steroid-resistant rejection, administration of ____ is the next step
antithymocte globulin; another option is off-label use of alemtuzumab
Can live vaccines be given post-transplant?
no!
Required vaccines are given pre-transplant if not up to date. Inactivated vaccines can be given post-transplant after ____ months.
Live vaccines cannot be give post transplant
3-6m
What are important vaccines for transplant patients?
flu annually
pneumococcal in adults >19y (PCV13 first if not received, PPSV23 at least 8 weeks later); subsequent doses of 23 should be in 5 years
Varicella vaccine (pre-transplant)
Tacrolimus is taken every ___ hours
12
and taken on an empty stomach! however, consistency is most important w or without food
