Transplant Flashcards by steph h

People with which type of blood are considered universal donors?

Type O

but can only receive type O blood

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People with Type A blood will react against what types of blood?

Type B and Type AB

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People with Type B blood will react against what types of blood?

Type A, Type AB

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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

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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

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A transplanted organ from a genetically identical donor (such as a twin) is called an ____

isograft

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A transplant in the same patient from one site to another

autograft - termed autologous transplant

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Induction immunosuppression is given BEFORE or at the time of transplant to …

prevent acute rejection during the early post-transplant period

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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

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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

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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

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This drug is off-label but can be used for induction

alemtuzumab

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Induction immunosuppression is not required if the transplant is from…

an identical twin

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Brand: Atgam - equine
Brand: Thymoglobulin - rabbit

Generic: antithymocyte Globulin

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This drug has a boxed warning for anaphylaxis

antithymocyte Globulin

*premedicate (Benadryl, Tylenol, steroids) to lessen infusion-related reactions

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Brand: Simulect

Generic: basiliximab (IL2 receptor antagonist)

well tolerated

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Maintenance immunosuppression is generally provided by the combination of:

a calcineurin inhibitor (CNI) +

an anti proliferative agent +/-

Steroids

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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

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Systemic steroids used

Prednisone typically

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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

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These drugs inhibit t lymphocyte proliferation by altering purine synthesis

anti proliferative agents

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What types of drugs are mycophenolate mofetil, and mycophenolic acid, and azathioprine?

anti proliferative agents

S/e: diarrhea, GI upset

NOT INTERCHANGEABLE

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Brand: CellCept

generic: mycophenolate mofetil

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Brand: Myfortic

Generic: mycophenolic acid

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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