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Therapeutics IV Final Subjects > Liver Transplant > Flashcards

Liver Transplant Flashcards

1
Q

What are some causes of ESLD?

A 
HCV
alcoholic cirrhosis
cryptogenic cirrhosis
autoimmmune hepatitis, HBV
primary biliary cirrhosis
biliary atresia
inborn erros of metabolism
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2
Q

What are some causes of ESLD?

A 
HCV
alcoholic cirrhosis
cryptogenic cirrhosis
autoimmmune hepatitis, HBV
primary biliary cirrhosis
biliary atresia
inborn erros of metabolism
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3
Q

Can you do cataberic or live liver transplantation?

A

yes

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4
Q

Is exta-hepatic malignancy a CI for Liver Transplant?

A

Yes

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5
Q

Is active infection and non compliance a CI for Liver Transplantation?

A

Yes and Yes

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6
Q

Is uncontrolled psychiatric disorder, and active substance abuse CI for liver transplantations?

A

Yes and yes

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7
Q

Is advance CAD CI in liver tranplants?

A

Yes

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8
Q

What is MELD score?

A

risk of dying while waiting for a transplant

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9
Q

Do you do HLB matching for Liver?

A

No , just ABO blood typing

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10
Q

What is rejection?

A

Immune response of the recipient to the transplanted organ resulting in allograft damage or failure

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11
Q

What is the difference between an acute rejection and a chronic rejection?

A

Acute: T-cell infiltration into the allograft, triggering inflammatory and cytotoxic effects
Chronic rejection: cytokine/cellular interactions, CD4+ and CD8+ T-cells, B-cells

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12
Q

What are some post transplant complications?

A 
Primary non-function
Hepatic artery thrombosis
Portal vein thrombosis
Biliary tract obstruction/leak
Recurrent disease (HBV, HCV)
Side effects
Rejections
Infections
malignancies
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13
Q

What are the three types of immunosuppressive regimes and their main goal?

A

1) Induction Therapy - for rejection prophylaxis
2) Maintenance Therapy - for rejection prophylaxis
3) Rescue Therapy - for tx of rejection

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14
Q

What pts get induction therapy?

A

pts at inc risk of rejections
pts who will receive CNI (calcenurin inhibitors) sparing regimens (renal transplant recipients and liver tranplant recipients with pre-transplant renal dysfunction)
pts who may receive steroid-sparing regimens

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15
Q

What does Induction therapy consist of?

A

A monoclonal Antibody - IL-2R Antagonist (basiliximab)
or
Polyclonal antibodies - ATG or RATG

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16
Q

What is the brand name of basiliximab?

A

Simulect

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17
Q

What is the MOA of basiliximab? And what is it used for?

A
  • binds to IL-2 receptors on activated T cells

- used for induction therapy of liver transplantation

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18
Q

What is the dose of basiliximab (Simulect)?

A

20mg IVPB before transplantation and 2nd dose 4 days after tx

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19
Q

Do you need premeds for basiliximab?

A

nope

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20
Q

Can Basiliximab cause cytokine releasing syndrome (CRS)?

A

No

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21
Q

What is the most common side effects of basiliximab?

A

GI (N/V/D)

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22
Q

how long do you infuse it and is it given via a central or peripheral line?

A

30 mins in a central OR peripheral line

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23
Q

ATG; what is the name and its MoA?

A

Derived from horse
Anti-thymocyte globulin (Atgam, ATG)
Binds to T cells and causes T cell depletion

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24
Q

What is RATG? name and MoA?

A

Rabbit Anti-thymocyte globulin (Thymoglobulin, RATG)
Derived from rabbit
MOA similar to ATG: binds to T cells and causes T cell depletion

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25
Q

What polyclonal antibody needs skin testing?

A

Anti-thymocyte globulin (Atgam, ATG)

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26
Q

What is the dosing of the two polyclonal antibodies?

A

ATG: 15-30mg/kg/day for 7-14 days
RATG: 1.5mg/kg/day for 7-14 days

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27
Q

How long must both polyclonal antibodies be infused over and should you use an in-line filter?

A

6 hours in a central line and yes you should use a filter and the first dose should be given in a monitored setting

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28
Q

What are some side effects of polyclonal antibodies?

A 
dec plt
dec WBC
fever, chills, rigors
rash, pruritis, urticaria
anaphylaxis
serum sickness
infections (viral)
malignancies

dd FaR SiM

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29
Q

What are the three maintenance therapy options?

A

1) Cyclosporine + steroid + MMForSirolimus
2) Tacrolimus + steroid + MMForSirolimus
3) Sirolimus + steroid + MMF

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30
Q

What is the function of CNIs (Calcineurin Inhibitors)

A

It blocks Calcineurin (which is used to activate T-cells)

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31
Q

Which two drugs act on Calcineurin?

A

1) Cyclosporine

2) Tacrolimus

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32
Q

Which two drugs act on TOR ?

A

Sirolimus and Evergolimus

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33
Q

Which two drugs act on the cell cycle?

A

Azathiaprine and Mycophenolate mofitil

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34
Q

What is the brand names of Cyclosporine?

A

SandImmune, Neoral, Gengraf

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35
Q

What is the MoA of Cyclosporine?

A

inhibits IL-2 production via calcineurin inhibition

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36
Q

What p450 CYP metabolizes cyclosporine?

A

3A4

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37
Q

What is the Oral to IV dose for cyclosporine?

A

IV is 1/3 the oral dose

1) IV 4-6mg/kg/day Continuous infusion or Q12h
2) Oral 4-12 mg/kd/day divided Q12h

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38
Q

Can you take cyclosporine with grapefruit?

A

No because it can inhibit 3A4 for up to 3 days

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39
Q

What brand name is not equivalent to the others for cyclosporine?

A

Neoral = Gengraf not equal to Sandimmune

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40
Q

What is the brand name of Tacrolimus?

A

Prograf

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41
Q

What is the MoA of Tacrolimus (Prograf)?

A

inhibits IL-2 production via calcineurin inhibition

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42
Q

Which is more potent cyclosporine or tacrolimus?

A

Tacrolimus

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43
Q

What enzyme metabolizes tacrolimus?

A

P450 CYP3A4

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44
Q

Can you give grapefruit juice with tacrolimus?

A

NO!

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45
Q

The compound is lipophilic and thus has highly variable oral %F. It also has high ______ and is mainly bound to erythrocytes

A

Protein binding (75%)

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46
Q

What is the oral to IV dose for Tacrolimus?

A

IV dose is 1/3 the oral dose.

1) IV 0.03-0.05mg/kd/day as a continuous infusion
2) Oral 0.1-0.3 mg/kg/day divided q12h

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47
Q

Which side effects are for both Cyclosporin and Tacrolimus?

A 
Nephrotoxicity
GI 
Hypomagnesemia
Hyperuricemia
Osteoporosis
Infections
Malignancies
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48
Q

Which side effects are for only Cyclosporine?

A

HTN
Hyperlipidemia
Gynecomastia
Hirsutism

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49
Q

What side effects are for only Tacrolimus?

A

Neurotoxicity
Hyperglycemia
Alopecia

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50
Q

What are some drug interactions with Cyclosporin and tacrolimus?

A 
Inc Levels of:Erythromycin, clarithromycin
fluconazole, itraconazole, voriconazole
diltiazem, verapamil
cimetidine, grapefruit juice
Dec Levels of: Antacids
phenytoin
carbamazepine
INH
rifampin
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51
Q

What drugs can cause synergistic nephrotoxicity?

A

NSAIDs and aminoglycosides

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52
Q

When taking cyclosporin and tacrolimus, what do you monitor for?

A 
monitor both trough of cyclosporine and tacrolimus
CNS side effects
blood glucose
bloop pressure
lipids
drug-drug and drug-food interaction
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53
Q

What is the trough level of tacrolimus?

A

5-20 ng/ml?

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54
Q

What is the trough level of cyclosporine?

A

100-450 ng/ml

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55
Q

What is the brand name of Sirolimus?

A

Rapamune

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56
Q

What is the MOA of Sirolimus (Rapamune)?

A

binds to the FKBP-12 and inhibits TOR (target of rapamycin) which results in suppression of cytokine-driven T-cell activation and proliferation

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57
Q

What enzyme metabolizes Sirolimus?

A

cytochrom P450 3A4

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58
Q

How protein bound is Sirolimus? So does it have a long half-life?

A

Lot, 92%; yes

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59
Q

How often do you dose Sirolimus?

A

Twice a week due to the long half-life

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60
Q

Can you take Sirolimus with Grapefruit juice?

A

No

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61
Q

How long after cyclosporine can you give Sirolimus?

A

4 hour separation

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62
Q

What are some side effects of Sirolimus? Which are BBW?

A

NOT nephrotoxic
Hyperlipidemia
Bone marrow suppresion: leukopenia, thrombocytopenia
Dec wound healing
Fatal reports of bronchial anastomotic dehisence in lung transplant pts
Fatal reports of hepatic artery thrombosis in liver transplant patients
Infections
Malignancies

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63
Q

What should you monitor for Sirolimus?

A 
Lipid Panel
CBC and platelets
Infection
Sirolimus trough of 5-15 ng/ml
Drug-drug and drug-food interactions
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64
Q

What is increased if you give concomitant Cyclosporine?

A

Sirolimus AUC and trough concentrations

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65
Q

What is the brand name of Everolimus?

A

Zortress

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66
Q

What is the MoA of Zortress? What is it used to tx?

A
  • binds to FKBP-12 and inhibits TOR which suppresses cytokine driven T-cell activation and proliferation
  • tx rejection prophylaxis in kidney transplantation
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67
Q

What enzyme breaks down Everolimus?

A

P450 Cyp3A4

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68
Q

What is the usual starting dose of Everolimus?

A

0.75mg PO q12h, adjusted every 4-5 days to target blood level

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69
Q

What is the target blood level of Everolimus?

A

3-8 ng/ml

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70
Q

Can you take Everolimus with our without food?

A

May be taken with or without food; do not chew or crush

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71
Q

Can you drink grapefruit juice with Everolimus?

A

No; increases levels

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72
Q

Avoid Standard doses of __________ in combination with everolimus due to increased risk of nephrotoxicity in renal transplantation

A

cyclosporine

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73
Q

What are three BBW for Everolimus?

A

Angioedema
Bone marrow suppression
Graft thrombosis - renal arterial and venous

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74
Q

What are some side effects of Everolimus?

A 
Peripheral edema
hyperlipidemia
HTN
hyperglycemia, new onset diabetes
inc risk of nephrotoxicity when co-administered with cyclosporine
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75
Q

What is the MoA of corticosteroids like Prednisone and methylprednisolone?

A 
inhibits cytokine production
IL-1
IL-2
IL-3
IL-6
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76
Q

What is a major problem with corticosteroids?

A

many acute and LONG-term side effects; part of most immunosuppressive regimes but now rapid steroid taper and steroid-free regimens are out there due to long-term side effects

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77
Q

What is the corticosteroid protocal @ Keck Hospital for transplantations?

A 
Methylprednisolone 0.5-1g IV during surgery
100mg IV q12h for 1 day
75 mg IV q12h for 1 day
50mg IV q12h for 1 day
25mg IV q12h for 1day
20mg IV QD
Prednisone 20mg PO daily
Mainteneance 2.5-5mg PO daily
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78
Q

What are the side effects of corticosteroids?

A 
Hyperlgycemia
hypertension
hyperlipidemia
weight gain/edema
Decreased wound healing
CNS
infections
sexual dysfunction
Acne/hirsutism
Cushingoid appearance
growth retardation
glaucoma
cataracts
osteoporosis
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79
Q

What are some monitoring parameters for corticosteroids?

A 
Blood pressure
lipid panel
blood sugar
weight
infections
annual eye exams
osteoporosis
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80
Q

What is the brand name of Azathioprine

A

Imuran

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81
Q

What is the MoA of Azathioprine?

A

inhibits B and T-lymphocyte proliferation by blocking purine synthesis

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82
Q

What is the brand name of mycophenolate?

A

Cellcept

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83
Q

What is the MoA of mycophenolate?

A

selectively blocks B and T-lymphocyte proliferation by inhibiting of IMPDH, a key enxyme in the de novo pathway of purine synthesis

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84
Q

What are the two purine antagonists for liver transplantation?

A

Azathiporine (Imuran) and Mycophenolate (Cellcept)

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85
Q

What is the post op dose of azathioprine?

A

3-5mg/kg/day IV

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86
Q

What is the mainenance dose of azathioprine?

A

1-3mg/kg/day PO

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87
Q

What is the conversion from IV to PO for azathioprine?

A

IV=PO

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88
Q

What is the dose and IV to PO conversion for Mycophenolate?

A

3g/day in 2 divided doses (1.5g q12h QD)

IV = PO

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89
Q

What are some side effects of Azathioprine (imuran)?

A 
Leukopenia
Thrombocytopenia
hepatotoxicity
infections
malignancies
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90
Q

What are some side effects of mycophenolate?

A 
GI - N/V/D/dyspepsia
Anemia
leukopenia
thrombocytopenia
infections
malignancies
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91
Q

What is the difference between Cellcept and Myfortic?

A

Cellcept is Mycophenolate mofetil, a pro-drug, that gets converted to Mycophenolic acid (Myfortic).
Myfortic is the active form (mycophenolic acid)

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92
Q

What are some drug interactions for Azathioprine?

A

Allopurinol (xanthine oxidase inhibitor: prevents metabolism of 6-MP)

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93
Q

What are some drug interactions for mycophenolate?

A

AL/Mg-containing antacids, cholestyramine (do not administer these together with mycophenolate because it will dec the Cmax and the AUC of MPA)
Acyclovir
Ganciclovir

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94
Q

How do you monitor Immune Fuction and how does it work?

A

Cylex ImmuKnow Assay; it measures the ATP levels in whole blood released from CD4 cells following cell stimulation:
525 is a high immune response (inc risk for rejection)

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95
Q

Why is a low and high immune response bad for tranplantation?

A

low indicates chance of infection while high indicates chance of rejection of transplanted organ

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96
Q

What is the brand name of Belatacept and what is it used for?

A

Nulojix

prophylaxis of acute rejection in KIDNEY transplant

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97
Q

What is the MoA of Belatacept (Nulojix)

A

selective T-cell co-stimulation blocker

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98
Q

You should use Belatacept (Nulojix) in combination with which three drugs?

A

Basiliximab (simulect) induction
Mycophenolate mofetil (cellcept)
carticosteroids (prednisone, methlyprednisolone)

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99
Q

Use belatacept only is pts who are EBV _____ because of an increased risk of what?

A

EBV positive

PTLD and b-cell lymphoma

100
Q

Which is less toxic, Belatacept or CNIs?

A

Beltacept

101
Q

Use in liver transplnat pts for belatacept is not recommended due to what?

A

an inc in risk of graft loss and death

102
Q

What has better CV and metabolic risk factors, CSA or belatacept?

A

belatacept; alot less side effects

103
Q

Do you need pre-meds for belatacept?

A

No

104
Q

Infuse belatacept over __ minutes with filter.

A

30 mins

105
Q

DO not infuse with other agents due to _______.

A

no compatibility information currently availible

106
Q

What are the most common ADRs of belatacept?

A

Anemia, leukopenia
D/N/V, HA, constipation
peripheral edema
hypokalemia, hyperkalemia

107
Q

What what are the options of Induction therapy?

A

CNIs
corticosteroids (methylprednisolone)
Antilymphocyte Ab - monoclonal (basiliximab) or polyclonal (ATG or RATG)

108
Q

What are the options for maintenance therapy?

A 
CNIs
corticosteroids (tapered)
Mycophenolate
azathioprine
Sirolimus
Evergolimus
109
Q

What are tx for rejection?

A

Bolus IV methlyprednisolone
antilymphocyte Ab - monoclonal (basiliximab), polyclonal (ATG, RATG)
CNIs

110
Q

What do you do for mild acute rejections?

A

inc dose of CSA or Tac
inc dose of prednisone
add an adjuctive (MMF, sirolimus)
switch from a less potent to a more potent agent (CSA –> Tac, or Azathiprine –.> MMF)

111
Q

What do you do for tx of moderate to severe acute rejection?

A

methylprednisolone 500-1000mg IV daily for 2-3 days followed by taper
for steroid-resistant rejections/steroid-avoidance use Thymoglobulin (RATG) or ATG (horse)

112
Q

For chronic rejection what do you do?

A 
CSA --> Tac
add Tac if not on a CNI
add MMF
add sirolimus
try to avoid over-immunosuppresion
113
Q

tx of refractory rejections

A 
inhaled CSA for refractory chronic rejection in lung transplant patients
immune globulin (IVIG) - used in heart and kidney transplant patients iwht refractory rejection
can be used to lower donor-specific alloantibody arising after transplantation
114
Q

What are some side effects of steroids?

A

diabetes, cataracts, infection, HTN, hyperlipidemia, osteroporosis, neurologic, cosmetic

115
Q

HCV pts at higher risk of recurrence with steroids?

A

yes

116
Q

“low-risk” pts may be candidates for withdrawl of steroids.

A

True

117
Q

what are some reason for CNIs avoidance

A

metabolic, CV, neurologic, and cosmetic effects

118
Q

In the CNI-sparing protocols, what do they use instead?

A

basiliximab (IL-2R antagonist)
Sirolimus
Evergolimus
MMF

119
Q

What are some risks of rejection?

A

1) ABO mismatch or positie crossmatch
2) HLA mismatches
3) High PRAs
4) prolonged ischemia time
5) subterapeutic immunosuppressive regimens
6) pts underlying disease
7) live vs cadaveric transplantation
8) retransplantation
9) ethnicity, multiple pregnancies
10) systemic infection post-transplant
11) cytomegalovirus infection
12) noncompliance - highest among adolescents

120
Q

What are some limitations to immunoisuppressive agents, I.E, what limits their use in us?

A

1) infectious complications
- pneumocysis penumonia
- HBV, HCV
- CMV: highest risk of CMV positive donars to CMV negative recipients:(prophylaxis w/ ganciclovir, valganciclovir

2) malignancies
- lymphomas
- squamous-cell carcinomas of the lip and skin
- incidence, timing of occurrence, and features of the tumors vary according to the immunosuppressive agents utilized

121
Q

What is PTLD?

A

Post-Transplant Lymphoproliferative Disorder - a lymphomas or cancer

122
Q

PTLD is strongly associated with what?

A

being Epstein-Barr negative (a DNA virus)

123
Q

What are some risk factors for PTLD?

A

presence and intensity of immunosuppressed state
primary infection with EBV
primary infection with CMV

124
Q

What is the treatment for PTLD?

A 
reduce or stop immunosuppressive therapy
give B-cell depleting monoclonal antibody (rituximab)
antiviral therapy
surgical resection
local irradication
chemotherapy
alpha-interferon, IVIG
125
Q

Can you do cataberic or live liver transplantation?

A

yes

126
Q

Is exta-hepatic malignancy a CI for Liver Transplant?

A

Yes

127
Q

Is active infection and non compliance a CI for Liver Transplantation?

A

Yes and Yes

128
Q

Is uncontrolled psychiatric disorder, and active substance abuse CI for liver transplantations?

A

Yes and yes

129
Q

Is advance CAD CI in liver tranplants?

A

Yes

130
Q

What is MELD score?

A

risk of dying while waiting for a transplant

131
Q

Do you do HLB matching for Liver?

A

No , just ABO blood typing

132
Q

What is rejection?

A

Immune response of the recipient to the transplanted organ resulting in allograft damage or failure

133
Q

What is the difference between an acute rejection and a chronic rejection?

A

Acute: T-cell infiltration into the allograft, triggering inflammatory and cytotoxic effects
Chronic rejection: cytokine/cellular interactions, CD4+ and CD8+ T-cells, B-cells

134
Q

What are some post transplant complications?

A 
Primary non-function
Hepatic artery thrombosis
Portal vein thrombosis
Biliary tract obstruction/leak
Recurrent disease (HBV, HCV)
Side effects
Rejections
Infections
malignancies
135
Q

What are the three types of immunosuppressive regimes and their main goal?

A

1) Induction Therapy - for rejection prophylaxis
2) Maintenance Therapy - for rejection prophylaxis
3) Rescue Therapy - for tx of rejection

136
Q

What pts get induction therapy?

A

pts at inc risk of rejections
pts who will receive CNI (calcenurin inhibitors) sparing regimens (renal transplant recipients and liver tranplant recipients with pre-transplant renal dysfunction)
pts who may receive steroid-sparing regimens

137
Q

What does Induction therapy consist of?

A

A monoclonal Antibody - IL-2R Antagonist (basiliximab)
or
Polyclonal antibodies - ATG or RATG

138
Q

What is the brand name of basiliximab?

A

Simulect

139
Q

What is the MOA of basiliximab? And what is it used for?

A
  • binds to IL-2 receptors on activated T cells

- used for induction therapy of liver transplantation

140
Q

What is the dose of basiliximab (Simulect)?

A

20mg IVPB before transplantation and 2nd dose 4 days after tx

141
Q

Do you need premeds for basiliximab?

A

nope

142
Q

Can Basiliximab cause cytokine releasing syndrome (CRS)?

A

No

143
Q

What is the most common side effects of basiliximab?

A

GI (N/V/D)

144
Q

how long do you infuse it and is it given via a central or peripheral line?

A

30 mins in a central OR peripheral line

145
Q

ATG; what is the name and its MoA?

A

Derived from horse
Anti-thymocyte globulin (Atgam, ATG)
Binds to T cells and causes T cell depletion

146
Q

What is RATG? name and MoA?

A

Rabbit Anti-thymocyte globulin (Thymoglobulin, RATG)
Derived from rabbit
MOA similar to ATG: binds to T cells and causes T cell depletion

147
Q

What polyclonal antibody needs skin testing?

A

Anti-thymocyte globulin (Atgam, ATG)

148
Q

What is the dosing of the two polyclonal antibodies?

A

ATG: 15-30mg/kg/day for 7-14 days
RATG: 1.5mg/kg/day for 7-14 days

149
Q

How long must both polyclonal antibodies be infused over and should you use an in-line filter?

A

6 hours in a central line and yes you should use a filter and the first dose should be given in a monitored setting

150
Q

What are some side effects of polyclonal antibodies?

A 
dec plt
dec WBC
fever, chills, rigors
rash, pruritis, urticaria
anaphylaxis
serum sickness
infections (viral)
malignancies

dd FaR SiM

151
Q

What are the three maintenance therapy options?

A

1) Cyclosporine + steroid + MMForSirolimus
2) Tacrolimus + steroid + MMForSirolimus
3) Sirolimus + steroid + MMF

152
Q

What is the function of CNIs (Calcineurin Inhibitors)

A

It blocks Calcineurin (which is used to activate T-cells)

153
Q

Which two drugs act on Calcineurin?

A

1) Cyclosporine

2) Tacrolimus

154
Q

Which two drugs act on TOR ?

A

Sirolimus and Evergolimus

155
Q

Which two drugs act on the cell cycle?

A

Azathiaprine and Mycophenolate mofitil

156
Q

What is the brand names of Cyclosporine?

A

SandImmune, Neoral, Gengraf

157
Q

What is the MoA of Cyclosporine?

A

inhibits IL-2 production via calcineurin inhibition

158
Q

What p450 CYP metabolizes cyclosporine?

A

3A4

159
Q

What is the Oral to IV dose for cyclosporine?

A

IV is 1/3 the oral dose

1) IV 4-6mg/kg/day Continuous infusion or Q12h
2) Oral 4-12 mg/kd/day divided Q12h

160
Q

Can you take cyclosporine with grapefruit?

A

No because it can inhibit 3A4 for up to 3 days

161
Q

What brand name is not equivalent to the others for cyclosporine?

A

Neoral = Gengraf not equal to Sandimmune

162
Q

What is the brand name of Tacrolimus?

A

Prograf

163
Q

What is the MoA of Tacrolimus (Prograf)?

A

inhibits IL-2 production via calcineurin inhibition

164
Q

Which is more potent cyclosporine or tacrolimus?

A

Tacrolimus

165
Q

What enzyme metabolizes tacrolimus?

A

P450 CYP3A4

166
Q

Can you give grapefruit juice with tacrolimus?

A

NO!

167
Q

The compound is lipophilic and thus has highly variable oral %F. It also has high ______ and is mainly bound to erythrocytes

A

Protein binding (75%)

168
Q

What is the oral to IV dose for Tacrolimus?

A

IV dose is 1/3 the oral dose.

1) IV 0.03-0.05mg/kd/day as a continuous infusion
2) Oral 0.1-0.3 mg/kg/day divided q12h

169
Q

Which side effects are for both Cyclosporin and Tacrolimus?

A 
Nephrotoxicity
GI 
Hypomagnesemia
Hyperuricemia
Osteoporosis
Infections
Malignancies
170
Q

Which side effects are for only Cyclosporine?

A

HTN
Hyperlipidemia
Gynecomastia
Hirsutism

171
Q

What side effects are for only Tacrolimus?

A

Neurotoxicity
Hyperglycemia
Alopecia

172
Q

What are some drug interactions with Cyclosporin and tacrolimus?

A 
Inc Levels of:Erythromycin, clarithromycin
fluconazole, itraconazole, voriconazole
diltiazem, verapamil
cimetidine, grapefruit juice
Dec Levels of: Antacids
phenytoin
carbamazepine
INH
rifampin
173
Q

What drugs can cause synergistic nephrotoxicity?

A

NSAIDs and aminoglycosides

174
Q

When taking cyclosporin and tacrolimus, what do you monitor for?

A 
monitor both trough of cyclosporine and tacrolimus
CNS side effects
blood glucose
bloop pressure
lipids
drug-drug and drug-food interaction
175
Q

What is the trough level of tacrolimus?

A

5-20 ng/ml?

176
Q

What is the trough level of cyclosporine?

A

100-450 ng/ml

177
Q

What is the brand name of Sirolimus?

A

Rapamune

178
Q

What is the MOA of Sirolimus (Rapamune)?

A

binds to the FKBP-12 and inhibits TOR (target of rapamycin) which results in suppression of cytokine-driven T-cell activation and proliferation

179
Q

What enzyme metabolizes Sirolimus?

A

cytochrom P450 3A4

180
Q

How protein bound is Sirolimus? So does it have a long half-life?

A

Lot, 92%; yes

181
Q

How often do you dose Sirolimus?

A

Twice a week due to the long half-life

182
Q

Can you take Sirolimus with Grapefruit juice?

A

No

183
Q

How long after cyclosporine can you give Sirolimus?

A

4 hour separation

184
Q

What are some side effects of Sirolimus? Which are BBW?

A

NOT nephrotoxic
Hyperlipidemia
Bone marrow suppresion: leukopenia, thrombocytopenia
Dec wound healing
Fatal reports of bronchial anastomotic dehisence in lung transplant pts
Fatal reports of hepatic artery thrombosis in liver transplant patients
Infections
Malignancies

185
Q

What should you monitor for Sirolimus?

A 
Lipid Panel
CBC and platelets
Infection
Sirolimus trough of 5-15 ng/ml
Drug-drug and drug-food interactions
186
Q

What is increased if you give concomitant Cyclosporine?

A

Sirolimus AUC and trough concentrations

187
Q

What is the brand name of Everolimus?

A

Zortress

188
Q

What is the MoA of Zortress? What is it used to tx?

A
  • binds to FKBP-12 and inhibits TOR which suppresses cytokine driven T-cell activation and proliferation
  • tx rejection prophylaxis in kidney transplantation
189
Q

What enzyme breaks down Everolimus?

A

P450 Cyp3A4

190
Q

What is the usual starting dose of Everolimus?

A

0.75mg PO q12h, adjusted every 4-5 days to target blood level

191
Q

What is the target blood level of Everolimus?

A

3-8 ng/ml

192
Q

Can you take Everolimus with our without food?

A

May be taken with or without food; do not chew or crush

193
Q

Can you drink grapefruit juice with Everolimus?

A

No; increases levels

194
Q

Avoid Standard doses of __________ in combination with everolimus due to increased risk of nephrotoxicity in renal transplantation

A

cyclosporine

195
Q

What are three BBW for Everolimus?

A

Angioedema
Bone marrow suppression
Graft thrombosis - renal arterial and venous

196
Q

What are some side effects of Everolimus?

A 
Peripheral edema
hyperlipidemia
HTN
hyperglycemia, new onset diabetes
inc risk of nephrotoxicity when co-administered with cyclosporine
197
Q

What is the MoA of corticosteroids like Prednisone and methylprednisolone?

A 
inhibits cytokine production
IL-1
IL-2
IL-3
IL-6
198
Q

What is a major problem with corticosteroids?

A

many acute and LONG-term side effects; part of most immunosuppressive regimes but now rapid steroid taper and steroid-free regimens are out there due to long-term side effects

199
Q

What is the corticosteroid protocal @ Keck Hospital for transplantations?

A 
Methylprednisolone 0.5-1g IV during surgery
100mg IV q12h for 1 day
75 mg IV q12h for 1 day
50mg IV q12h for 1 day
25mg IV q12h for 1day
20mg IV QD
Prednisone 20mg PO daily
Mainteneance 2.5-5mg PO daily
200
Q

What are the side effects of corticosteroids?

A 
Hyperlgycemia
hypertension
hyperlipidemia
weight gain/edema
Decreased wound healing
CNS
infections
sexual dysfunction
Acne/hirsutism
Cushingoid appearance
growth retardation
glaucoma
cataracts
osteoporosis
201
Q

What are some monitoring parameters for corticosteroids?

A 
Blood pressure
lipid panel
blood sugar
weight
infections
annual eye exams
osteoporosis
202
Q

What is the brand name of Azathioprine

A

Imuran

203
Q

What is the MoA of Azathioprine?

A

inhibits B and T-lymphocyte proliferation by blocking purine synthesis

204
Q

What is the brand name of mycophenolate?

A

Cellcept

205
Q

What is the MoA of mycophenolate?

A

selectively blocks B and T-lymphocyte proliferation by inhibiting of IMPDH, a key enxyme in the de novo pathway of purine synthesis

206
Q

What are the two purine antagonists for liver transplantation?

A

Azathiporine (Imuran) and Mycophenolate (Cellcept)

207
Q

What is the post op dose of azathioprine?

A

3-5mg/kg/day IV

208
Q

What is the mainenance dose of azathioprine?

A

1-3mg/kg/day PO

209
Q

What is the conversion from IV to PO for azathioprine?

A

IV=PO

210
Q

What is the dose and IV to PO conversion for Mycophenolate?

A

3g/day in 2 divided doses (1.5g q12h QD)

IV = PO

211
Q

What are some side effects of Azathioprine (imuran)?

A 
Leukopenia
Thrombocytopenia
hepatotoxicity
infections
malignancies
212
Q

What are some side effects of mycophenolate?

A 
GI - N/V/D/dyspepsia
Anemia
leukopenia
thrombocytopenia
infections
malignancies
213
Q

What is the difference between Cellcept and Myfortic?

A

Cellcept is Mycophenolate mofetil, a pro-drug, that gets converted to Mycophenolic acid (Myfortic).
Myfortic is the active form (mycophenolic acid)

214
Q

What are some drug interactions for Azathioprine?

A

Allopurinol (xanthine oxidase inhibitor: prevents metabolism of 6-MP)

215
Q

What are some drug interactions for mycophenolate?

A

AL/Mg-containing antacids, cholestyramine (do not administer these together with mycophenolate because it will dec the Cmax and the AUC of MPA)
Acyclovir
Ganciclovir

216
Q

How do you monitor Immune Fuction and how does it work?

A

Cylex ImmuKnow Assay; it measures the ATP levels in whole blood released from CD4 cells following cell stimulation:
525 is a high immune response (inc risk for rejection)

217
Q

Why is a low and high immune response bad for tranplantation?

A

low indicates chance of infection while high indicates chance of rejection of transplanted organ

218
Q

What is the brand name of Belatacept and what is it used for?

A

Nulojix

prophylaxis of acute rejection in KIDNEY transplant

219
Q

What is the MoA of Belatacept (Nulojix)

A

selective T-cell co-stimulation blocker

220
Q

You should use Belatacept (Nulojix) in combination with which three drugs?

A

Basiliximab (simulect) induction
Mycophenolate mofetil (cellcept)
carticosteroids (prednisone, methlyprednisolone)

221
Q

Use belatacept only is pts who are EBV _____ because of an increased risk of what?

A

EBV positive

PTLD and b-cell lymphoma

222
Q

Which is less toxic, Belatacept or CNIs?

A

Beltacept

223
Q

Use in liver transplnat pts for belatacept is not recommended due to what?

A

an inc in risk of graft loss and death

224
Q

What has better CV and metabolic risk factors, CSA or belatacept?

A

belatacept; alot less side effects

225
Q

Do you need pre-meds for belatacept?

A

No

226
Q

Infuse belatacept over __ minutes with filter.

A

30 mins

227
Q

DO not infuse with other agents due to _______.

A

no compatibility information currently availible

228
Q

What are the most common ADRs of belatacept?

A

Anemia, leukopenia
D/N/V, HA, constipation
peripheral edema
hypokalemia, hyperkalemia

229
Q

What what are the options of Induction therapy?

A

CNIs
corticosteroids (methylprednisolone)
Antilymphocyte Ab - monoclonal (basiliximab) or polyclonal (ATG or RATG)

230
Q

What are the options for maintenance therapy?

A 
CNIs
corticosteroids (tapered)
Mycophenolate
azathioprine
Sirolimus
Evergolimus
231
Q

What are tx for rejection?

A

Bolus IV methlyprednisolone
antilymphocyte Ab - monoclonal (basiliximab), polyclonal (ATG, RATG)
CNIs

232
Q

What do you do for mild acute rejections?

A

inc dose of CSA or Tac
inc dose of prednisone
add an adjuctive (MMF, sirolimus)
switch from a less potent to a more potent agent (CSA –> Tac, or Azathiprine –.> MMF)

233
Q

What do you do for tx of moderate to severe acute rejection?

A

methylprednisolone 500-1000mg IV daily for 2-3 days followed by taper
for steroid-resistant rejections/steroid-avoidance use Thymoglobulin (RATG) or ATG (horse)

234
Q

For chronic rejection what do you do?

A 
CSA --> Tac
add Tac if not on a CNI
add MMF
add sirolimus
try to avoid over-immunosuppresion
235
Q

tx of refractory rejections

A 
inhaled CSA for refractory chronic rejection in lung transplant patients
immune globulin (IVIG) - used in heart and kidney transplant patients iwht refractory rejection
can be used to lower donor-specific alloantibody arising after transplantation
236
Q

What are some side effects of steroids?

A

diabetes, cataracts, infection, HTN, hyperlipidemia, osteroporosis, neurologic, cosmetic

237
Q

HCV pts at higher risk of recurrence with steroids?

A

yes

238
Q

“low-risk” pts may be candidates for withdrawl of steroids.

A

True

239
Q

what are some reason for CNIs avoidance

A

metabolic, CV, neurologic, and cosmetic effects

240
Q

In the CNI-sparing protocols, what do they use instead?

A

basiliximab (IL-2R antagonist)
Sirolimus
Evergolimus
MMF

241
Q

What are some risks of rejection?

A

1) ABO mismatch or positie crossmatch
2) HLA mismatches
3) High PRAs
4) prolonged ischemia time
5) subterapeutic immunosuppressive regimens
6) pts underlying disease
7) live vs cadaveric transplantation
8) retransplantation
9) ethnicity, multiple pregnancies
10) systemic infection post-transplant
11) cytomegalovirus infection
12) noncompliance - highest among adolescents

242
Q

What are some limitations to immunoisuppressive agents, I.E, what limits their use in us?

A

1) infectious complications
- pneumocysis penumonia
- HBV, HCV
- CMV: highest risk of CMV positive donars to CMV negative recipients:(prophylaxis w/ ganciclovir, valganciclovir

2) malignancies
- lymphomas
- squamous-cell carcinomas of the lip and skin
- incidence, timing of occurrence, and features of the tumors vary according to the immunosuppressive agents utilized

243
Q

What is PTLD?

A

Post-Transplant Lymphoproliferative Disorder - a lymphomas or cancer

244
Q

PTLD is strongly associated with what?

A

being Epstein-Barr negative (a DNA virus)

245
Q

What are some risk factors for PTLD?

A

presence and intensity of immunosuppressed state
primary infection with EBV
primary infection with CMV

246
Q

What is the treatment for PTLD?

A 
reduce or stop immunosuppressive therapy
give B-cell depleting monoclonal antibody (rituximab)
antiviral therapy
surgical resection
local irradication
chemotherapy
alpha-interferon, IVIG

Therapeutics IV Final Subjects (10 decks)

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