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

Lecture 1 - Transplant Immunosupression Flashcards

(88 cards)

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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
Cyclosporine MOA basics
Blocks calcineuron, cant produce more inflammatory cytokines Binds to cyclophillin
26
Tacrolimus formulations
Prograf = IR Envarsus XR = once dialy Astragraf XL = once daily
27
Prograf dosing
0.1-0.2 mg/kg/day orally in 2 equally divided doses...12hrs apart
28
Prograf IV dose adjustment
1/3 to 1/5 of oral dose
29
Sublingual Prograf dose adjustment
1/2 of oral dose
30
Tacrolimus monitoring
trough monitoring, goals of 5-12
31
Tacrolimus DI
CYP3A4, caution w/ inducers and inhibitors
32
Sublingual Tacrolimus info
Given to someone who is NPO or N/V Essentially take capsule, open and pour under tongue give 1/2 of oral dose
33
major side effect of tacrolimus?
Tremor, occurs in 30-50% of kidney transplant occurs at peak tacrolimus concentrations
34
Benefits seen with Envarsus Tacrolimus?
Reduced peak = less tremors Longer time to T max Higher bioavail Less % fluctuations in troughs
35
Prograf to Envarsus XR dose
Reduce Total daily dose by 20%
36
Prograf to Astagraf XL dose
increase total daily dose by 8%
37
Are Tacrolimus formulations interchangeable?
Nah
38
what to do if Tacrolimus lvls 2 X target...
hold 1 dose then resume new dose
39
What to do if Tacrolimus lvls >2 X target....
hold at least 2 doses then resume new dose
40
How to adjust Tacrolimus dose
Dnew/Cssnew = Dold/Css old solve for what you need
41
Cyclosporine Modified (Neoral) vs Cyclosporine (Sandimmune)
Neoral: inc absorption & bioavailability Sandimmune: Erratic/incomplete absorption, reduced bioavail
42
Cyclosporine dosing
5-10mg/kg/day divided into 2 equal doses IV dose is 1/3 of total oral = usually dont use
43
Can you give cyclosporine SL?
nah
44
What to monitor on cyclosporine
Check troughs, but peak lvls show better data
45
Cyclosporine DI
caution with CYP3A4 inhibitor of transport proteins
46
C2 monitoring Cylclosporine
2 hours after dose you get peak, has good correlation with AUC but have 10-15min window
47
Cyclosporine troughts
usually 250-350 after transplant maintain 100-150 after
48
Tacrolimus ADE
Neurotoxicity Changes in electrolytes, Hair loss
49
Cyclosporine ADE
More nephrotoxic worse cardiovascular profile can cause hair growth Risk of Gingival hyperplasia not preferred
50
Electrolyte abnormalities CNI
Hyperkalemia** = need to reduce Hypomag, phosphorus, calcium so have to supplement
51
Sirolimus/Everolimus Basic MOA
Inhibition of T cell response to cytokines Inhibits proliferation at G1 to S phase
52
Which MTOR inhibitors are transplant indication
Zortress Rapamune
53
Which MTOR inhibitors are cancer indication
Afinitor
54
Sirolimus (Rapamune) dosing & info
2-4mg QD Tab or solution monitor trough in AM 67hr 1/2life = awhile to see dose change, check every 7-14 day
55
Everolimus (Zortress) dosing & info
0.75-1mg BID Check trough in morning 38hr 1/2life = 3-5 day checking trough
56
Sirolimus & Everolimus DI
Cyp3A4 Caution w/ inhibitors and inducers
57
Sirolimus & Everolimus warnings
Black box = Hepatic and renal artery thrombosis, not used at discharge Can lead to bronchial anastomotic dehiscence dont use at time of transplant
58
Common indications for sirolimus/Everolimus (mTORi)
Refractory rejection Minimize CNI toxicity, if cant tolerate CAV protection certain viral infections cancer, skin = big 1
59
Switching between mTORi
takes awhile to do once get to target lvl, reduce the other drug you want to d/c
60
mTOR side effects that require D/c
Pneumonitis Angioedema
61
mTORi side effects
Pneumontis** Angioedema*** Proteinuria thrombosis Impaired wound healing Leukopenia/Anemia Rash/acne Hyperlipidemia/hypertriglyceridemia
62
mTORi ulcer info
big issue usually have to start on some type of steroids within 1st 2 weeks of starting drug
63
Can pts use NSAIDs after transplant?
nah try to avoid also try to avoid immune system supplements
64
Potent CYP3A4 inhibitors
HIV booster = ritonavir/cobicistat Paxlovid -Azole antifungals Erythromycin/Clarithromycin Diltz/Verapamil Grapefruit juice CBD need to Dec dose to account for inc exposure
65
Potent CYP3A4 inducers
Phenytoin, Carbamazepine, Phenobarbital Rifampin, Rifapentine Nafcillin St.johns wart Need to Inc dose to account for dec exposure
66
Antiproliferatives
2nd line agents Mycophenolate mofetil & sodium Azathioprine
67
Mycophenolate MOA
blocks pathway that produces purines, cant make DNA/RNA specific to T/B cells
68
Mycophenolate Mofetil (Cellcept) Dosing
1000mg BID IV:Oral is 1:1
69
Myocphenolate Sodium (Myfortic) Dosing
720mg BID coated tab so cant crush, etc
70
Do you need to do levels for Mycophenolate
nah, no use
71
Adverse effects of Mycophenolate
Mostly GI = N/V/D/heartburn Myfortic was made to reduce these Marrow suppression Preg category D
72
Mycophenolate DI
dont have to worry about CYP3A4 inhibitors/inducers AL,Mg, Calcium, try to separate by 2-4hrs
73
Cellcept to Myfortic conversion?
1000mg cellcept = 720 myfortic
74
IV mycophenolate conversion?
720mg myfortic = 1000mg cellcept = 1000mg IV
75
Impact of diarrhea on Tacrolimus lvls
with diarrhea, speed that tacrolimus moves through GI tract increases bypass area that metabolizes drug ** inc tacrolimus lvls**
76
Is Mycophenolate on REMS?
Yes all REMS guidelines apply
77
Azathioprine Basic MOA
inhibits purine production
78
Azathioprine dosing
usually use 1-1.5mg/kg/day
79
Azathioprine Side effects
marrow suppression** thrombocytopenia, leukopenia, anemia Fewer GI effects
80
When to use Azathioprine
when want to get preg or cant tolerate Mycophenolate
81
What sort of testing do you need for Azathioprine
TPMT testing, need to have function of that enzyme
82
DI Azathioprine
Xanthine oxidase inhibitors CI w/ febuxostat avoid allopurinol, or dec AZA dose by 67%
83
Co-stimulation blockers
Belatacept
84
Belatacept MOA
Blocks 2nd signal activating T cell between CD80/86 and CD28 receptor
85
Belatacept Dosing
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
Belatacept cant be used in someone who is...
EBV negative
87
what organs is Belatacept approved for?
Kidneys not approved for organs outside of that
88
Corticosteroid uses
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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