Solid Organ Transplantation Flashcards by Mckenna Fiew

What is the average wait time for a kidney transplant?

4 years - long because we have dialysis

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What is the average wait time for a liver transplant?

1 year

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What is the average wait time for a heart transplant?

6 months- more critical

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What are the 3 kinds of therapy associated with immunosuppression?

Induction therapy
Maintenance therapy
Rejection Therapy

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What is induction therapy?

an intense level of immunosuppression at time of transplant

- Can allow delay of nephrotoxic calcineurin inhibitors

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What is maintenance therapy?

Highly individualized therapy

Can be reduced as risk for rejection decreases

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What is rejection therapy?

Used to decrease immune response and prevent allograft damage

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What are 4 induction therapy agents?

Anti-thrombocyte globulin (thymogobulin)
Basiliximab
Alemtuzimab
methylprednisolone

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What is the brand name of anti-thrombocyte globulin?

Thymoglobulin

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What kind of antibody is thymoglobulin?

polyclonal rabbit

Depleting (depletes T cells)

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What is the mechanism of thymoglobulin?

Binds to lymphocytes and causes lysis and depletion of lymphocytes

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What kind of therapy is thymoglobulin used in?

induction and rejection treatment

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What are some ADE of thymoglobulin?

myelosuppression
anaphylaxis
hypo/hpertension
tachycardia
dyspnea
urticaria 
rash

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What conditions require dose adjustment for thymoglobulin?

thrombocytopenia

leukopenia

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How do you prevent infusion site reactions?

pretreat with acetaminophen, diphenhydramine and steroids

-central line administration/slow infusion rate

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What are some dosing/administration characteristics of thymoglobulin?

IV through central line
Requires 0.22 micron filter
1st dose over 6 hrs, rest over 4hrs

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What is the brand name of alemtuzumab?

Campath

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What is the mechanism of action of alemtuzumb?

Depletes both T and B lymphocytes by binding to CD52 and causing cell lysis

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What is alemtuzumab’s place in therapy?

transplant induction therapy and acute rejection therapy

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How is alemtuzumab dosed?

Single dose at time of transplant (IV)

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What are some ADEs of alemtuzumb?

Infusion related rxns- pretreat

myeosuppression

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What kind of antibody is alemtuzumab?

depleting antibody

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what kind of antibody is basilixumab?

non depleting antibody

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What is the brand name of basilixumab

simulect

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What is the mechanism of action of basilixumab?

IL-2 receptor antagonist by binding to CD25 on T lymphocytes and prevents IL-2 activation and proliferation of t cells.

Where is basilixumab's place in therapy?

induction therapy

What are some ADEs of basilixumab?

not associated with infusion related reactions | hypersensitivity reactions

What are some dosing and administration characteristics of basilixumab?

2 doses IV, central or peripheral, over 30 min

What are 3 types of maintenance immunosuppressants?

Calcineurin inhibitors antiproliferative agents steroids

What kind of maintenance therapy is cyclosporine?

calcineurin inhibitor

What kind of maintenance therapy is tacrolimus?

calcineurin inhibitor

What is the mechanism of action of calcineurin inhibitors?

Block cell T-cell proliferation by inhaling production of IL-2 and other cytokines

What is the place of therapy in calcineurin inhibitors?

prevent organ rejection | cornerstone of immunosupression protocols

How can cyclosporine be dosed/administered?

``` IV 1/3 daily dose cyclosporine - continuous or BID infusion tacrolimus- continuous infusion PO- q 12hrs for IR, 24 hrs for ER SL_ tacrolimus only every 12 hrs ```

How are concentrations of calcineurin inhibitors monitored?

trough blood concentrations every 12 hours | - goal dependent on organ, time post transplant, protecols

What are the ADEs of calcineurin inhibitors?

``` dose related nephrotoxicity electrolyte abnormalities neurotoxicity- tremors, HA, neuropathy, seizures Cosmetic effects metabolic- HTN, HLD, hyperglycemia ```

What kind of cosmetic effects does cyclosporine cause?

hirsuitism, ginvival, hyperplasia

What kind of cosmetic effect does tacrolimus cause?

alopecia

What kind of electrolyte abnormalities can tacrolimus cause?

hyperkalemia | hypomagnesemia

What drugs increase the concentration of calcinurine inhibitors?

``` Azole antifungals macrolide antibiotics calcium channel blockers anti-retrovirals grapefruit juice *CYP inhibitors ```

What drugs decrease the concentration of calcinurine inhibitors?

``` phenytoin phenobarbital rifampin rifabutin St. John's Wort ```

Which CYP enzyme metabolizes calcineurin inhibitors?

CYP3A4

Which drug class does mycophenolate mofetil belong too?

antiproliferative agents

what is the brand name of mycophenolate mofetil?

CellCept

what class of drugs does mycophenolte sodium belong too?

antiproliferative agents

what is the brand name of mycophenolate sodium?

Myfortic

What class of drugs does azthioprine belong too?

antiproliferative agents

what is the brand name of azthioprine?

Imuran

what is the dosing and administration of mycophenolate mofetil?

same IV and PO q 12hrs

What is the dosing and administration of mycophenolate sodium?

Only PO q 12 hrs

What is the dose conversion betweek myco. mofetil and myco. sodium?

720 mg sodium = 1000 mg mofetil

What is the dosing and admin of azathioprione?

same dose IV and PO q 24 hrs

What are the ADEs of antiproliferative agents?

N/V, diarrhea, abdominal pain | anemia, leukopenia, thrombocytopenia

What are ADEs of azathioprine specifically?

hepatotoxicity, pancreatitis

How can we deal with GI side effects of antiproliferatives?

reduce dose, divide doses, take with food, start low and increase dose as needed

Which antiproloferative has a REMS program?

mycophenolate | for pregnancy

What are some drug interactions with mycophenolate?

iron, Mg, Al, Cholestyramine all decrease the absorption of mycophenolate separate by 2-4 hours

What are some drug interactions with azathioprine?

Allopurinol inhibits xanthine oxidase (used in azthioprine metabolism) increases risk of bone marrow suppression

By how much does azathioprine need to be increased or reduced by when taking concurrently with allopurinol?

Reduce by 50-75%

What are the two corticosteroids used in immunosupression therapy?

methylprednisolone -Solu-Medrol | prednisone- Deltasone

What is the mechanism of action of steroids?

block cytokine activation and interfere with cell migration, recognition and has cytotoxic effector mechanisms

What is the dosing/admin of steroids?

usually begins IV methylpred then tapered to PO prednisone then tapered to minimally effective dose

What are the metabolic ADEs of corticosteroids?

HTN HLD hyperglycemia osteoporosis

What are some cosmetic ADEs of corticosteroids?

``` moon face buffalo hump thin skin cataracts increased appetite weight gain hirsutism ```

What are the psychological effects of corticosteroids?

insomnia | mood swings

What drug class does sirolimus belong too?

rapamycin inhibitors

what drug class does everolimus belong too?

rapamycin inhibitors

What is the mechanism of rapamycin inhibitors?

inhibits the cellular response to IL-2 and progression of the cell cylce

What is the place in therapy of rapamycin inhibitors?

in place of CNI to decrease nephrotoxicity | slow progression of vasculopathy after heart transplant

What are the dosing/admin of sirolimus?

QD dosing May or may not use a loading dose Only PO Dose based on serum concentrations - 24 hr trough

What is the dosing/admin of everolimus?

BID dosing only PO dose based on serum concentrations- 24 hr trough

What are some ADEs of rapamycin inhibitors?

``` myelosuppression hypercholesterolemia hypertriglyceridemia delayed wound healing mouth ulcers reversible interstitial pneumonitis rash/acne/diarrhea/arthralgia proteinuria ```

What class of drugs does Belatacept (Nulojix) belong too?

costimulation blocker

What is the mechanism of action of belatacept?

binds to CD80/86 pm APC cells blocking CD28 costimulation of T cells

When is belatacept used in therapy?

prevent rejection of kidney in patients who are positive for EBV replace CNI in conjunction with an antiproliferative and steroids

What is the dosing/admin of belatacept?

Initially- 10mg/kg IV day of transplant prior to surgery, on day 5, and end of weeks 2, 4, 8, 12 Maintenance- 5mg/kg at end of week 16 and q 4 weeks IV over 30 min

What are the ADEs of costimulation blockers?

``` Anemia, leukopenia N/V, diarrhea, constipation peripheral edema fever, cough, HA HTN Hyperkalemia, hypokalemia infection malignancy ```

What are the 4 kinds of rejection?

hyperacute acute cellular antibody mediated chronic