Immunosuppressants Kinetics Exam 4

What are the indications for immunosuppressants

1. solid organ transplant

2. immune mediated disorders

3. oncology

What are the two classifications of medications for solid organ transplant

1. induction

2. maintenance

What are the risks of over immunosuppression

1. infection

2. malignancy

3. drug toxicity

what are risks of under-immunosuppression

rejection

What are the three key induction medications

1. anti-thrymocyte globulin

2. alemtuzumab

3. basiliximab

Although the half lives of induction agents are _________, the duration of effect can last __________

hours/days, weeks to months

Duration of effect for induction immunosuppressant agents ___________ the half life elimination of the drug from the body

far exceeds

when using anti-thymocyte globulin, you may do what in terms of dosing

not administer a dose on the day of discharge from the hospital to expedite discharge

when using basiliximab, you may do what in terms of dosing

administer the second dose after discharge to expedite discharge and facilitate reimbursement

Why can you base basiliximab and anti-thymocyte globulin dosing based on discharge time

the duration of effect far exceeds the half life elimination of the drug from the body

what are the calcineurin inhibitors

1. tacrolimus

2. cyclosporin

The bioavailability of cyclosporin is __________ than tacrolimus

lower

Why do calcineurin inhibitors have a low bioavailability

1. incomplete/variable absorption

2. extensive first pass metabolism

what was the point of creating a modified cyclosporin

increase bioavailability

Oral doses of immediate release calcineurin inhibitors are dosed ________

twice daily

IV doses of calcineurin inhibitors are given how

continuous infusion over 24 hours

What is the IV to PO conversion of cyclosporin

IV = 1/3 daily PO dose

What is the IV to PO conversion of tacrolimus

IV = 1/4 total daily PO dose

What is the max dose of tacrolimus

4mg/day

Metabolism of calcineurin inhibitors is

extensively hepatic

in a patient with AKI taking a calcineurin inhibitors, what should you do

nothing, it is hepatically metabolized

Although ________ can CAUSE AKI, the are not renally excreted

calcineurin inhibitors

What CYP is responsible for metabolism of calcineurin inhibitors

CYP3A4

When starting a CYP3A4 inhibitor in a patient stable on calcineurin inhibitor.....

decreased the dose of the calcineurin inhibitor

When stopping a CYP3A4 inhibitor in a patient stable on a calcineurin inhibitor....

increase the dose of the calcineurin inhibitor

CYP3A4 inducers _________ the metabolism of calcineurin inhibitors, which __________ the serum concentrations of calcineurin inhibitors

increase, decrease

list common CYP3A4 inhibitors

1. azoles

2. macrolides

3. protease inhibitors

4. grapefruit juice

If a patient develops diarrhea after being on a calcineurin inhibitor....

decrease the dose of the calcineurin inhibitor

a patient with diarrhea may have less _________ which leads to increased concentrations of calcineurin inhibitors and potential for ________

P-glycoprotein, toxicity

cyclosporin is a _______ of _______

weak inhibitor of CYP3A4

calcineurin inhibitors have ________ between plasma concentration and adverse effects

good correlation

Which medication has a good correlation between its trough level and its AUC

tacrolimus

1 multiple choice option

if you wanted to draw a cyclosporin level that correlates well with the patient's true AUC, when would you need to draw the level

2 hours after they take the medication

Trough goals of calcineurin inhibitors are....

highly variable

if a patient has tremors with prograf, what may you want to transition them to and why?

envarsus XR because it has a lower peak and more steady PK profile

When transitioning to envarsus from prograf, you may need to

decrease the dose

Because calcineurin inhibitors follow linear PK, when you have a peak and a dose and you have a certain goal peak, how can you determine your new dose?

simple ratio/proportion

mycophenolate is an

antiproliferate (of T cells)

What is true about first pass metabolism of mycophenolate

results in the active metabolite

mycophenolate undergoes __________

enterohepatic recirculation

The IV:PO convertion for mycophenolate modefetil is

1:1

What is the MMF:MPA conversion

1000mg:720mg

Which has less GI symptoms

Myfortic

1 multiple choice option

_______ blocks the enterohepatic recirculation of mycophenolic acid while _______ dose not

cyclosporin, tacrolimus

__________ of mycophenolate are recommended when using in combination with cyclosporin

higher

Adverse effects of mycophenolate associated with high peaks

1. low white blood cell count

2. GI issues

If mycophenolate mofetil is being dose at 1000mg BID and the patient is experiencing diarrhea, how could you reduce the peak levels without reducing the overall dose?

split the dose to 500mg QID

t/f: mycophenolate is not a narrow therapeutic index drug and does not display drastic inter/intra patient variability

true

1 multiple choice option

is therapeutic drug monitoring used for mycophenolate?

no

select the mTOR inhibitors

1. sirolimus

2. everolimus

in terms of excretion, sirolimus and everolimus are

extensively hepatically metabolized

In terms of metabolism, sirolimus and everolimus are

major substrates of CYP3A4 and P-glycoprotein

therapeutic drug monitoring (can/cannot) be used for sirolimus/everolimus

can

1 multiple choice option

ADR seen with sirolimus or everolimus

1. leukopenia

2. ulcers

3. proteinuria

4. impaired wound healing

goal ranges of sirolimus/everolimus are _______ when used in combination with a calcineurin inhibitor than when used alone

lower

how long should you wait to draw a trough level for sirolimus after a dosage change?

1 week

how long should you wait to draw a trough level for everolimus after a dosage change?

5 days

Which medication may require a loading dose

sirolimus

3 multiple choice options

When would you need to consider the long half lives of sirolimus/everolimus?

1. discontinuing due to adverse effects

2. need for surgery

Which medication displays non-linear kinetics

sirolimus

3 multiple choice options

sirolimus has a half life of

about 60 hours