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CDM 3 Exam 3 > Lecture 1 - Transplant Immunosupression > Flashcards

Lecture 1 - Transplant Immunosupression Flashcards

1
Q

Induction Agent general info

A

potent
used at time of transplant, and few days after

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2
Q

Maintenance Agents general info

A

live long agents

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3
Q

Rejection Treatment general info

A

used for rejection..duh

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4
Q

Available induction agents

A

Monoclonal antibodies:
Alemtuzmab (Campath) = T cell depleting
Basiliximab (Simulect) = Non-T cell depleting

Polyclonal:
Equine anti-thymocyte globulin (ATGAM) = T cell depleting
Rabbit anti-thymocyte globulin (Thymoglobulin) = T cell depleting

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5
Q

Basiliximab (Simulect) info

A

Monoclonal
Non-depleting
Targets IL-2 receptor

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6
Q

Basiliximab (simplest) dosing info

A

20mg IV on Day 0 and 4

No need for premedication

half life 7 days, in body for 3-5weeks b4 need maintenance therapy

Good for pts high risk for complications too much immunosuppression

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7
Q

What receptors do Anti-Thymocyte Globulins target

A

CD28
IL-2
CD3
CD4
T cell receptor

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8
Q

Which Anti-Thymocyte Globulin is used in transplant pts? Horse or rabbit

A

Rabbit, shown to be superior in preventing rejection
Horse has a lot of toxicities too

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9
Q

Anti-Thymocyte Globulin rabbit dosing

A

1-1.5mg/kg/day

Induction = 3-5 doses
Rejection = 5-7 doses

req premed with steroids, Benadryl, Tylenol

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10
Q

Anti-Thymocyte Globulin Rabbit adverse reactions

A

Malignancy + infection
Infusion associated reactions
Leukopenia + thrombocytopenia

Half dose = WBC 2-3, platelets 50-75
Hold dose = WBC < 3, platelets < 50

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11
Q

How long for immune system to rebound Anti-Thymocyte Globulin rabbit?

A

2-3 months, takes awhile

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12
Q

Serum sickness Anti-Thymocyte Globulin Rabbit

A

4-14 days after exposure to med
inc risk if prior rabbit exposure
can lead to renal dysfunction through the formation of Ab-Ag complexes

Fever, myalgia, artralgia, malaise,itchy skin, rash

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13
Q

Infusion related Reactions Anti-Thymocyte Globulin Rabbit

A

occurs with 1/2nd infusion, manageable w/ reduce in infusion rate

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14
Q

Alemtuzumab (Campath) targets what receptor

A

CD52

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15
Q

Alemtuzumab (Campath) Dosing

A

30mg X 1 at transplant

Premed req w/ steroids, Benadryl, tylenol

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16
Q

Alemtuzumab (Campath) Adverse reactions

A

Leukopenia
Malignancy + infections
Infusion reactions if IV

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17
Q

Alemtuzumab (Campath) considerations

A

profound depletion of lymphocytes that can last up to 1 yr

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18
Q

Alemtuzumab (Campath) requirement for therapy

A

centers have to be enrolled in cam path distribution program

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19
Q

When is Thyroglobulin or Campath preferred?

A

High immunologic risk patients

ie…. young, autoimmune disease, steroid withdrawal protocols

** Low risk for complications of immunosuppression***

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20
Q

When is Simulect preferred?

A

Low immunologic risk patients

ie… 1 haplotype match (sibling/parent), > 70yrs, prior cancer/infection/organ transplant

** high risk for complications of immunosuppression ***

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21
Q

Primary agents maintenance

A

Tacrolimus***
Cylcosporine
Belatacept
Sirolimus
Everolimus

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22
Q

Secondary Agents maintenance

A

Mycophenolate mofetil/sodium***
Azathioprine
Everolimus
Sirolimus

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23
Q

Tertiary agent maintenance

A

+/- corticosteroids

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24
Q

Tacrolimus MOA basics

A

Blocks calcineuron, cant produce more inflammatory cytokines

binds to FKBP

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25
Q

Cyclosporine MOA basics

A

Blocks calcineuron, cant produce more inflammatory cytokines

Binds to cyclophillin

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26
Q

Tacrolimus formulations

A

Prograf = IR
Envarsus XR = once dialy
Astragraf XL = once daily

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27
Q

Prograf dosing

A

0.1-0.2 mg/kg/day orally in 2 equally divided doses…12hrs apart

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28
Q

Prograf IV dose adjustment

A

1/3 to 1/5 of oral dose

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29
Q

Sublingual Prograf dose adjustment

A

1/2 of oral dose

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30
Q

Tacrolimus monitoring

A

trough monitoring, goals of 5-12

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31
Q

Tacrolimus DI

A

CYP3A4, caution w/ inducers and inhibitors

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32
Q

Sublingual Tacrolimus info

A

Given to someone who is NPO or N/V

Essentially take capsule, open and pour under tongue

give 1/2 of oral dose

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33
Q

major side effect of tacrolimus?

A

Tremor, occurs in 30-50% of kidney transplant

occurs at peak tacrolimus concentrations

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34
Q

Benefits seen with Envarsus Tacrolimus?

A

Reduced peak = less tremors
Longer time to T max
Higher bioavail
Less % fluctuations in troughs

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35
Q

Prograf to Envarsus XR dose

A

Reduce Total daily dose by 20%

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36
Q

Prograf to Astagraf XL dose

A

increase total daily dose by 8%

37
Q

Are Tacrolimus formulations interchangeable?

A

Nah

38
Q

what to do if Tacrolimus lvls 2 X target…

A

hold 1 dose then resume new dose

39
Q

What to do if Tacrolimus lvls >2 X target….

A

hold at least 2 doses then resume new dose

40
Q

How to adjust Tacrolimus dose

A

Dnew/Cssnew = Dold/Css old

solve for what you need

41
Q

Cyclosporine Modified (Neoral) vs Cyclosporine (Sandimmune)

A

Neoral: inc absorption & bioavailability

Sandimmune: Erratic/incomplete absorption, reduced bioavail

42
Q

Cyclosporine dosing

A

5-10mg/kg/day divided into 2 equal doses
IV dose is 1/3 of total oral = usually dont use

43
Q

Can you give cyclosporine SL?

A

nah

44
Q

What to monitor on cyclosporine

A

Check troughs, but peak lvls show better data

45
Q

Cyclosporine DI

A

caution with CYP3A4
inhibitor of transport proteins

46
Q

C2 monitoring Cylclosporine

A

2 hours after dose you get peak, has good correlation with AUC but have 10-15min window

47
Q

Cyclosporine troughts

A

usually 250-350 after transplant

maintain 100-150 after

48
Q

Tacrolimus ADE

A

Neurotoxicity
Changes in electrolytes,
Hair loss

49
Q

Cyclosporine ADE

A

More nephrotoxic
worse cardiovascular profile
can cause hair growth
Risk of Gingival hyperplasia
not preferred

50
Q

Electrolyte abnormalities CNI

A

Hyperkalemia** = need to reduce

Hypomag, phosphorus, calcium so have to supplement

51
Q

Sirolimus/Everolimus Basic MOA

A

Inhibition of T cell response to cytokines

Inhibits proliferation at G1 to S phase

52
Q

Which MTOR inhibitors are transplant indication

A

Zortress
Rapamune

53
Q

Which MTOR inhibitors are cancer indication

A

Afinitor

54
Q

Sirolimus (Rapamune) dosing & info

A

2-4mg QD

Tab or solution
monitor trough in AM
67hr 1/2life = awhile to see dose change, check every 7-14 day

55
Q

Everolimus (Zortress) dosing & info

A

0.75-1mg BID

Check trough in morning
38hr 1/2life = 3-5 day checking trough

56
Q

Sirolimus & Everolimus DI

A

Cyp3A4
Caution w/ inhibitors and inducers

57
Q

Sirolimus & Everolimus warnings

A

Black box = Hepatic and renal artery thrombosis, not used at discharge

Can lead to bronchial anastomotic dehiscence

dont use at time of transplant

58
Q

Common indications for sirolimus/Everolimus (mTORi)

A

Refractory rejection
Minimize CNI toxicity, if cant tolerate
CAV protection
certain viral infections
cancer, skin = big 1

59
Q

Switching between mTORi

A

takes awhile to do

once get to target lvl, reduce the other drug you want to d/c

60
Q

mTOR side effects that require D/c

A

Pneumonitis
Angioedema

61
Q

mTORi side effects

A

Pneumontis**
Angioedema***

Proteinuria
thrombosis
Impaired wound healing
Leukopenia/Anemia
Rash/acne
Hyperlipidemia/hypertriglyceridemia

62
Q

mTORi ulcer info

A

big issue
usually have to start on some type of steroids
within 1st 2 weeks of starting drug

63
Q

Can pts use NSAIDs after transplant?

A

nah try to avoid
also try to avoid immune system supplements

64
Q

Potent CYP3A4 inhibitors

A

HIV booster = ritonavir/cobicistat
Paxlovid
-Azole antifungals
Erythromycin/Clarithromycin
Diltz/Verapamil
Grapefruit juice
CBD

need to Dec dose to account for inc exposure

65
Q

Potent CYP3A4 inducers

A

Phenytoin, Carbamazepine, Phenobarbital
Rifampin, Rifapentine
Nafcillin
St.johns wart

Need to Inc dose to account for dec exposure

66
Q

Antiproliferatives

A

2nd line agents

Mycophenolate mofetil & sodium
Azathioprine

67
Q

Mycophenolate MOA

A

blocks pathway that produces purines, cant make DNA/RNA

specific to T/B cells

68
Q

Mycophenolate Mofetil (Cellcept) Dosing

A

1000mg BID
IV:Oral is 1:1

69
Q

Myocphenolate Sodium (Myfortic) Dosing

A

720mg BID
coated tab so cant crush, etc

70
Q

Do you need to do levels for Mycophenolate

A

nah, no use

71
Q

Adverse effects of Mycophenolate

A

Mostly GI = N/V/D/heartburn
Myfortic was made to reduce these
Marrow suppression

Preg category D

72
Q

Mycophenolate DI

A

dont have to worry about CYP3A4 inhibitors/inducers

AL,Mg, Calcium, try to separate by 2-4hrs

73
Q

Cellcept to Myfortic conversion?

A

1000mg cellcept = 720 myfortic

74
Q

IV mycophenolate conversion?

A

720mg myfortic = 1000mg cellcept = 1000mg IV

75
Q

Impact of diarrhea on Tacrolimus lvls

A

with diarrhea, speed that tacrolimus moves through GI tract increases
bypass area that metabolizes drug
** inc tacrolimus lvls**

76
Q

Is Mycophenolate on REMS?

A

Yes
all REMS guidelines apply

77
Q

Azathioprine Basic MOA

A

inhibits purine production

78
Q

Azathioprine dosing

A

usually use 1-1.5mg/kg/day

79
Q

Azathioprine Side effects

A

marrow suppression** thrombocytopenia, leukopenia, anemia
Fewer GI effects

80
Q

When to use Azathioprine

A

when want to get preg or cant tolerate Mycophenolate

81
Q

What sort of testing do you need for Azathioprine

A

TPMT testing, need to have function of that enzyme

82
Q

DI Azathioprine

A

Xanthine oxidase inhibitors

CI w/ febuxostat
avoid allopurinol, or dec AZA dose by 67%

83
Q

Co-stimulation blockers

A

Belatacept

84
Q

Belatacept MOA

A

Blocks 2nd signal activating T cell between CD80/86 and CD28 receptor

85
Q

Belatacept Dosing

A

IV only

higher dose during initial
maintenance dose is every 4 weeks

dose adjustment only if weight changes by > 10% from initial, and have to be able to divide dose by 12.5mg

IV infusion over 30min

V well tolerated

86
Q

Belatacept cant be used in someone who is…

A

EBV negative

87
Q

what organs is Belatacept approved for?

A

Kidneys
not approved for organs outside of that

88
Q

Corticosteroid uses

A

dosing varies, but tend to use higher doses during transplant/rejection and lower for maintenance

CDM 3 Exam 3 (9 decks)

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