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Therapeutics IV Final Subjects > Liver Transplant > Flashcards

Liver Transplant Flashcards

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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
What polyclonal antibody needs skin testing?
Anti-thymocyte globulin (Atgam, ATG)
26
What is the dosing of the two polyclonal antibodies?
ATG: 15-30mg/kg/day for 7-14 days RATG: 1.5mg/kg/day for 7-14 days
27
How long must both polyclonal antibodies be infused over and should you use an in-line filter?
6 hours in a central line and yes you should use a filter and the first dose should be given in a monitored setting
28
What are some side effects of polyclonal antibodies?
``` dec plt dec WBC fever, chills, rigors rash, pruritis, urticaria anaphylaxis serum sickness infections (viral) malignancies ``` dd FaR SiM
29
What are the three maintenance therapy options?
1) Cyclosporine + steroid + MMForSirolimus 2) Tacrolimus + steroid + MMForSirolimus 3) Sirolimus + steroid + MMF
30
What is the function of CNIs (Calcineurin Inhibitors)
It blocks Calcineurin (which is used to activate T-cells)
31
Which two drugs act on Calcineurin?
1) Cyclosporine | 2) Tacrolimus
32
Which two drugs act on TOR ?
Sirolimus and Evergolimus
33
Which two drugs act on the cell cycle?
Azathiaprine and Mycophenolate mofitil
34
What is the brand names of Cyclosporine?
SandImmune, Neoral, Gengraf
35
What is the MoA of Cyclosporine?
inhibits IL-2 production via calcineurin inhibition
36
What p450 CYP metabolizes cyclosporine?
3A4
37
What is the Oral to IV dose for cyclosporine?
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
38
Can you take cyclosporine with grapefruit?
No because it can inhibit 3A4 for up to 3 days
39
What brand name is not equivalent to the others for cyclosporine?
Neoral = Gengraf not equal to Sandimmune
40
What is the brand name of Tacrolimus?
Prograf
41
What is the MoA of Tacrolimus (Prograf)?
inhibits IL-2 production via calcineurin inhibition
42
Which is more potent cyclosporine or tacrolimus?
Tacrolimus
43
What enzyme metabolizes tacrolimus?
P450 CYP3A4
44
Can you give grapefruit juice with tacrolimus?
NO!
45
The compound is lipophilic and thus has highly variable oral %F. It also has high ______ and is mainly bound to erythrocytes
Protein binding (75%)
46
What is the oral to IV dose for Tacrolimus?
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
47
Which side effects are for both Cyclosporin and Tacrolimus?
``` Nephrotoxicity GI Hypomagnesemia Hyperuricemia Osteoporosis Infections Malignancies ```
48
Which side effects are for only Cyclosporine?
HTN Hyperlipidemia Gynecomastia Hirsutism
49
What side effects are for only Tacrolimus?
Neurotoxicity Hyperglycemia Alopecia
50
What are some drug interactions with Cyclosporin and tacrolimus?
``` Inc Levels of:Erythromycin, clarithromycin fluconazole, itraconazole, voriconazole diltiazem, verapamil cimetidine, grapefruit juice Dec Levels of: Antacids phenytoin carbamazepine INH rifampin ```
51
What drugs can cause synergistic nephrotoxicity?
NSAIDs and aminoglycosides
52
When taking cyclosporin and tacrolimus, what do you monitor for?
``` monitor both trough of cyclosporine and tacrolimus CNS side effects blood glucose bloop pressure lipids drug-drug and drug-food interaction ```
53
What is the trough level of tacrolimus?
5-20 ng/ml?
54
What is the trough level of cyclosporine?
100-450 ng/ml
55
What is the brand name of Sirolimus?
Rapamune
56
What is the MOA of Sirolimus (Rapamune)?
binds to the FKBP-12 and inhibits TOR (target of rapamycin) which results in suppression of cytokine-driven T-cell activation and proliferation
57
What enzyme metabolizes Sirolimus?
cytochrom P450 3A4
58
How protein bound is Sirolimus? So does it have a long half-life?
Lot, 92%; yes
59
How often do you dose Sirolimus?
Twice a week due to the long half-life
60
Can you take Sirolimus with Grapefruit juice?
No
61
How long after cyclosporine can you give Sirolimus?
4 hour separation
62
What are some side effects of Sirolimus? Which are BBW?
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
63
What should you monitor for Sirolimus?
``` Lipid Panel CBC and platelets Infection Sirolimus trough of 5-15 ng/ml Drug-drug and drug-food interactions ```
64
What is increased if you give concomitant Cyclosporine?
Sirolimus AUC and trough concentrations
65
What is the brand name of Everolimus?
Zortress
66
What is the MoA of Zortress? What is it used to tx?
- binds to FKBP-12 and inhibits TOR which suppresses cytokine driven T-cell activation and proliferation - tx rejection prophylaxis in kidney transplantation
67
What enzyme breaks down Everolimus?
P450 Cyp3A4
68
What is the usual starting dose of Everolimus?
0.75mg PO q12h, adjusted every 4-5 days to target blood level
69
What is the target blood level of Everolimus?
3-8 ng/ml
70
Can you take Everolimus with our without food?
May be taken with or without food; do not chew or crush
71
Can you drink grapefruit juice with Everolimus?
No; increases levels
72
Avoid Standard doses of __________ in combination with everolimus due to increased risk of nephrotoxicity in renal transplantation
cyclosporine
73
What are three BBW for Everolimus?
Angioedema Bone marrow suppression Graft thrombosis - renal arterial and venous
74
What are some side effects of Everolimus?
``` Peripheral edema hyperlipidemia HTN hyperglycemia, new onset diabetes inc risk of nephrotoxicity when co-administered with cyclosporine ```
75
What is the MoA of corticosteroids like Prednisone and methylprednisolone?
``` inhibits cytokine production IL-1 IL-2 IL-3 IL-6 ```
76
What is a major problem with corticosteroids?
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
77
What is the corticosteroid protocal @ Keck Hospital for transplantations?
``` 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 ```
78
What are the side effects of corticosteroids?
``` Hyperlgycemia hypertension hyperlipidemia weight gain/edema Decreased wound healing CNS infections sexual dysfunction Acne/hirsutism Cushingoid appearance growth retardation glaucoma cataracts osteoporosis ```
79
What are some monitoring parameters for corticosteroids?
``` Blood pressure lipid panel blood sugar weight infections annual eye exams osteoporosis ```
80
What is the brand name of Azathioprine
Imuran
81
What is the MoA of Azathioprine?
inhibits B and T-lymphocyte proliferation by blocking purine synthesis
82
What is the brand name of mycophenolate?
Cellcept
83
What is the MoA of mycophenolate?
selectively blocks B and T-lymphocyte proliferation by inhibiting of IMPDH, a key enxyme in the de novo pathway of purine synthesis
84
What are the two purine antagonists for liver transplantation?
Azathiporine (Imuran) and Mycophenolate (Cellcept)
85
What is the post op dose of azathioprine?
3-5mg/kg/day IV
86
What is the mainenance dose of azathioprine?
1-3mg/kg/day PO
87
What is the conversion from IV to PO for azathioprine?
IV=PO
88
What is the dose and IV to PO conversion for Mycophenolate?
3g/day in 2 divided doses (1.5g q12h QD) | IV = PO
89
What are some side effects of Azathioprine (imuran)?
``` Leukopenia Thrombocytopenia hepatotoxicity infections malignancies ```
90
What are some side effects of mycophenolate?
``` GI - N/V/D/dyspepsia Anemia leukopenia thrombocytopenia infections malignancies ```
91
What is the difference between Cellcept and Myfortic?
Cellcept is Mycophenolate mofetil, a pro-drug, that gets converted to Mycophenolic acid (Myfortic). Myfortic is the active form (mycophenolic acid)
92
What are some drug interactions for Azathioprine?
Allopurinol (xanthine oxidase inhibitor: prevents metabolism of 6-MP)
93
What are some drug interactions for mycophenolate?
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
94
How do you monitor Immune Fuction and how does it work?
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)
95
Why is a low and high immune response bad for tranplantation?
low indicates chance of infection while high indicates chance of rejection of transplanted organ
96
What is the brand name of Belatacept and what is it used for?
Nulojix | prophylaxis of acute rejection in KIDNEY transplant
97
What is the MoA of Belatacept (Nulojix)
selective T-cell co-stimulation blocker
98
You should use Belatacept (Nulojix) in combination with which three drugs?
Basiliximab (simulect) induction Mycophenolate mofetil (cellcept) carticosteroids (prednisone, methlyprednisolone)
99
Use belatacept only is pts who are EBV _____ because of an increased risk of what?
EBV positive | PTLD and b-cell lymphoma
100
Which is less toxic, Belatacept or CNIs?
Beltacept
101
Use in liver transplnat pts for belatacept is not recommended due to what?
an inc in risk of graft loss and death
102
What has better CV and metabolic risk factors, CSA or belatacept?
belatacept; alot less side effects
103
Do you need pre-meds for belatacept?
No
104
Infuse belatacept over __ minutes with filter.
30 mins
105
DO not infuse with other agents due to _______.
no compatibility information currently availible
106
What are the most common ADRs of belatacept?
Anemia, leukopenia D/N/V, HA, constipation peripheral edema hypokalemia, hyperkalemia
107
What what are the options of Induction therapy?
CNIs corticosteroids (methylprednisolone) Antilymphocyte Ab - monoclonal (basiliximab) or polyclonal (ATG or RATG)
108
What are the options for maintenance therapy?
``` CNIs corticosteroids (tapered) Mycophenolate azathioprine Sirolimus Evergolimus ```
109
What are tx for rejection?
Bolus IV methlyprednisolone antilymphocyte Ab - monoclonal (basiliximab), polyclonal (ATG, RATG) CNIs
110
What do you do for mild acute rejections?
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
What do you do for tx of moderate to severe acute rejection?
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
For chronic rejection what do you do?
``` CSA --> Tac add Tac if not on a CNI add MMF add sirolimus try to avoid over-immunosuppresion ```
113
tx of refractory rejections
``` 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
What are some side effects of steroids?
diabetes, cataracts, infection, HTN, hyperlipidemia, osteroporosis, neurologic, cosmetic
115
HCV pts at higher risk of recurrence with steroids?
yes
116
"low-risk" pts may be candidates for withdrawl of steroids.
True
117
what are some reason for CNIs avoidance
metabolic, CV, neurologic, and cosmetic effects
118
In the CNI-sparing protocols, what do they use instead?
basiliximab (IL-2R antagonist) Sirolimus Evergolimus MMF
119
What are some risks of rejection?
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
What are some limitations to immunoisuppressive agents, I.E, what limits their use in us?
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
What is PTLD?
Post-Transplant Lymphoproliferative Disorder - a lymphomas or cancer
122
PTLD is strongly associated with what?
being Epstein-Barr negative (a DNA virus)
123
What are some risk factors for PTLD?
presence and intensity of immunosuppressed state primary infection with EBV primary infection with CMV
124
What is the treatment for PTLD?
``` reduce or stop immunosuppressive therapy give B-cell depleting monoclonal antibody (rituximab) antiviral therapy surgical resection local irradication chemotherapy alpha-interferon, IVIG ```
125
Can you do cataberic or live liver transplantation?
yes
126
Is exta-hepatic malignancy a CI for Liver Transplant?
Yes
127
Is active infection and non compliance a CI for Liver Transplantation?
Yes and Yes
128
Is uncontrolled psychiatric disorder, and active substance abuse CI for liver transplantations?
Yes and yes
129
Is advance CAD CI in liver tranplants?
Yes
130
What is MELD score?
risk of dying while waiting for a transplant
131
Do you do HLB matching for Liver?
No , just ABO blood typing
132
What is rejection?
Immune response of the recipient to the transplanted organ resulting in allograft damage or failure
133
What is the difference between an acute rejection and a chronic rejection?
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
What are some post transplant complications?
``` Primary non-function Hepatic artery thrombosis Portal vein thrombosis Biliary tract obstruction/leak Recurrent disease (HBV, HCV) Side effects Rejections Infections malignancies ```
135
What are the three types of immunosuppressive regimes and their main goal?
1) Induction Therapy - for rejection prophylaxis 2) Maintenance Therapy - for rejection prophylaxis 3) Rescue Therapy - for tx of rejection
136
What pts get induction therapy?
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
What does Induction therapy consist of?
A monoclonal Antibody - IL-2R Antagonist (basiliximab) or Polyclonal antibodies - ATG or RATG
138
What is the brand name of basiliximab?
Simulect
139
What is the MOA of basiliximab? And what is it used for?
- binds to IL-2 receptors on activated T cells | - used for induction therapy of liver transplantation
140
What is the dose of basiliximab (Simulect)?
20mg IVPB before transplantation and 2nd dose 4 days after tx
141
Do you need premeds for basiliximab?
nope
142
Can Basiliximab cause cytokine releasing syndrome (CRS)?
No
143
What is the most common side effects of basiliximab?
GI (N/V/D)
144
how long do you infuse it and is it given via a central or peripheral line?
30 mins in a central OR peripheral line
145
ATG; what is the name and its MoA?
Derived from horse Anti-thymocyte globulin (Atgam, ATG) Binds to T cells and causes T cell depletion
146
What is RATG? name and MoA?
Rabbit Anti-thymocyte globulin (Thymoglobulin, RATG) Derived from rabbit MOA similar to ATG: binds to T cells and causes T cell depletion
147
What polyclonal antibody needs skin testing?
Anti-thymocyte globulin (Atgam, ATG)
148
What is the dosing of the two polyclonal antibodies?
ATG: 15-30mg/kg/day for 7-14 days RATG: 1.5mg/kg/day for 7-14 days
149
How long must both polyclonal antibodies be infused over and should you use an in-line filter?
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
What are some side effects of polyclonal antibodies?
``` dec plt dec WBC fever, chills, rigors rash, pruritis, urticaria anaphylaxis serum sickness infections (viral) malignancies ``` dd FaR SiM
151
What are the three maintenance therapy options?
1) Cyclosporine + steroid + MMForSirolimus 2) Tacrolimus + steroid + MMForSirolimus 3) Sirolimus + steroid + MMF
152
What is the function of CNIs (Calcineurin Inhibitors)
It blocks Calcineurin (which is used to activate T-cells)
153
Which two drugs act on Calcineurin?
1) Cyclosporine | 2) Tacrolimus
154
Which two drugs act on TOR ?
Sirolimus and Evergolimus
155
Which two drugs act on the cell cycle?
Azathiaprine and Mycophenolate mofitil
156
What is the brand names of Cyclosporine?
SandImmune, Neoral, Gengraf
157
What is the MoA of Cyclosporine?
inhibits IL-2 production via calcineurin inhibition
158
What p450 CYP metabolizes cyclosporine?
3A4
159
What is the Oral to IV dose for cyclosporine?
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
Can you take cyclosporine with grapefruit?
No because it can inhibit 3A4 for up to 3 days
161
What brand name is not equivalent to the others for cyclosporine?
Neoral = Gengraf not equal to Sandimmune
162
What is the brand name of Tacrolimus?
Prograf
163
What is the MoA of Tacrolimus (Prograf)?
inhibits IL-2 production via calcineurin inhibition
164
Which is more potent cyclosporine or tacrolimus?
Tacrolimus
165
What enzyme metabolizes tacrolimus?
P450 CYP3A4
166
Can you give grapefruit juice with tacrolimus?
NO!
167
The compound is lipophilic and thus has highly variable oral %F. It also has high ______ and is mainly bound to erythrocytes
Protein binding (75%)
168
What is the oral to IV dose for Tacrolimus?
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
Which side effects are for both Cyclosporin and Tacrolimus?
``` Nephrotoxicity GI Hypomagnesemia Hyperuricemia Osteoporosis Infections Malignancies ```
170
Which side effects are for only Cyclosporine?
HTN Hyperlipidemia Gynecomastia Hirsutism
171
What side effects are for only Tacrolimus?
Neurotoxicity Hyperglycemia Alopecia
172
What are some drug interactions with Cyclosporin and tacrolimus?
``` Inc Levels of:Erythromycin, clarithromycin fluconazole, itraconazole, voriconazole diltiazem, verapamil cimetidine, grapefruit juice Dec Levels of: Antacids phenytoin carbamazepine INH rifampin ```
173
What drugs can cause synergistic nephrotoxicity?
NSAIDs and aminoglycosides
174
When taking cyclosporin and tacrolimus, what do you monitor for?
``` monitor both trough of cyclosporine and tacrolimus CNS side effects blood glucose bloop pressure lipids drug-drug and drug-food interaction ```
175
What is the trough level of tacrolimus?
5-20 ng/ml?
176
What is the trough level of cyclosporine?
100-450 ng/ml
177
What is the brand name of Sirolimus?
Rapamune
178
What is the MOA of Sirolimus (Rapamune)?
binds to the FKBP-12 and inhibits TOR (target of rapamycin) which results in suppression of cytokine-driven T-cell activation and proliferation
179
What enzyme metabolizes Sirolimus?
cytochrom P450 3A4
180
How protein bound is Sirolimus? So does it have a long half-life?
Lot, 92%; yes
181
How often do you dose Sirolimus?
Twice a week due to the long half-life
182
Can you take Sirolimus with Grapefruit juice?
No
183
How long after cyclosporine can you give Sirolimus?
4 hour separation
184
What are some side effects of Sirolimus? Which are BBW?
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
What should you monitor for Sirolimus?
``` Lipid Panel CBC and platelets Infection Sirolimus trough of 5-15 ng/ml Drug-drug and drug-food interactions ```
186
What is increased if you give concomitant Cyclosporine?
Sirolimus AUC and trough concentrations
187
What is the brand name of Everolimus?
Zortress
188
What is the MoA of Zortress? What is it used to tx?
- binds to FKBP-12 and inhibits TOR which suppresses cytokine driven T-cell activation and proliferation - tx rejection prophylaxis in kidney transplantation
189
What enzyme breaks down Everolimus?
P450 Cyp3A4
190
What is the usual starting dose of Everolimus?
0.75mg PO q12h, adjusted every 4-5 days to target blood level
191
What is the target blood level of Everolimus?
3-8 ng/ml
192
Can you take Everolimus with our without food?
May be taken with or without food; do not chew or crush
193
Can you drink grapefruit juice with Everolimus?
No; increases levels
194
Avoid Standard doses of __________ in combination with everolimus due to increased risk of nephrotoxicity in renal transplantation
cyclosporine
195
What are three BBW for Everolimus?
Angioedema Bone marrow suppression Graft thrombosis - renal arterial and venous
196
What are some side effects of Everolimus?
``` Peripheral edema hyperlipidemia HTN hyperglycemia, new onset diabetes inc risk of nephrotoxicity when co-administered with cyclosporine ```
197
What is the MoA of corticosteroids like Prednisone and methylprednisolone?
``` inhibits cytokine production IL-1 IL-2 IL-3 IL-6 ```
198
What is a major problem with corticosteroids?
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
What is the corticosteroid protocal @ Keck Hospital for transplantations?
``` 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
What are the side effects of corticosteroids?
``` Hyperlgycemia hypertension hyperlipidemia weight gain/edema Decreased wound healing CNS infections sexual dysfunction Acne/hirsutism Cushingoid appearance growth retardation glaucoma cataracts osteoporosis ```
201
What are some monitoring parameters for corticosteroids?
``` Blood pressure lipid panel blood sugar weight infections annual eye exams osteoporosis ```
202
What is the brand name of Azathioprine
Imuran
203
What is the MoA of Azathioprine?
inhibits B and T-lymphocyte proliferation by blocking purine synthesis
204
What is the brand name of mycophenolate?
Cellcept
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What is the MoA of mycophenolate?
selectively blocks B and T-lymphocyte proliferation by inhibiting of IMPDH, a key enxyme in the de novo pathway of purine synthesis
206
What are the two purine antagonists for liver transplantation?
Azathiporine (Imuran) and Mycophenolate (Cellcept)
207
What is the post op dose of azathioprine?
3-5mg/kg/day IV
208
What is the mainenance dose of azathioprine?
1-3mg/kg/day PO
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What is the conversion from IV to PO for azathioprine?
IV=PO
210
What is the dose and IV to PO conversion for Mycophenolate?
3g/day in 2 divided doses (1.5g q12h QD) | IV = PO
211
What are some side effects of Azathioprine (imuran)?
``` Leukopenia Thrombocytopenia hepatotoxicity infections malignancies ```
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What are some side effects of mycophenolate?
``` GI - N/V/D/dyspepsia Anemia leukopenia thrombocytopenia infections malignancies ```
213
What is the difference between Cellcept and Myfortic?
Cellcept is Mycophenolate mofetil, a pro-drug, that gets converted to Mycophenolic acid (Myfortic). Myfortic is the active form (mycophenolic acid)
214
What are some drug interactions for Azathioprine?
Allopurinol (xanthine oxidase inhibitor: prevents metabolism of 6-MP)
215
What are some drug interactions for mycophenolate?
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
How do you monitor Immune Fuction and how does it work?
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
Why is a low and high immune response bad for tranplantation?
low indicates chance of infection while high indicates chance of rejection of transplanted organ
218
What is the brand name of Belatacept and what is it used for?
Nulojix | prophylaxis of acute rejection in KIDNEY transplant
219
What is the MoA of Belatacept (Nulojix)
selective T-cell co-stimulation blocker
220
You should use Belatacept (Nulojix) in combination with which three drugs?
Basiliximab (simulect) induction Mycophenolate mofetil (cellcept) carticosteroids (prednisone, methlyprednisolone)
221
Use belatacept only is pts who are EBV _____ because of an increased risk of what?
EBV positive | PTLD and b-cell lymphoma
222
Which is less toxic, Belatacept or CNIs?
Beltacept
223
Use in liver transplnat pts for belatacept is not recommended due to what?
an inc in risk of graft loss and death
224
What has better CV and metabolic risk factors, CSA or belatacept?
belatacept; alot less side effects
225
Do you need pre-meds for belatacept?
No
226
Infuse belatacept over __ minutes with filter.
30 mins
227
DO not infuse with other agents due to _______.
no compatibility information currently availible
228
What are the most common ADRs of belatacept?
Anemia, leukopenia D/N/V, HA, constipation peripheral edema hypokalemia, hyperkalemia
229
What what are the options of Induction therapy?
CNIs corticosteroids (methylprednisolone) Antilymphocyte Ab - monoclonal (basiliximab) or polyclonal (ATG or RATG)
230
What are the options for maintenance therapy?
``` CNIs corticosteroids (tapered) Mycophenolate azathioprine Sirolimus Evergolimus ```
231
What are tx for rejection?
Bolus IV methlyprednisolone antilymphocyte Ab - monoclonal (basiliximab), polyclonal (ATG, RATG) CNIs
232
What do you do for mild acute rejections?
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
What do you do for tx of moderate to severe acute rejection?
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
For chronic rejection what do you do?
``` CSA --> Tac add Tac if not on a CNI add MMF add sirolimus try to avoid over-immunosuppresion ```
235
tx of refractory rejections
``` 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
What are some side effects of steroids?
diabetes, cataracts, infection, HTN, hyperlipidemia, osteroporosis, neurologic, cosmetic
237
HCV pts at higher risk of recurrence with steroids?
yes
238
"low-risk" pts may be candidates for withdrawl of steroids.
True
239
what are some reason for CNIs avoidance
metabolic, CV, neurologic, and cosmetic effects
240
In the CNI-sparing protocols, what do they use instead?
basiliximab (IL-2R antagonist) Sirolimus Evergolimus MMF
241
What are some risks of rejection?
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
What are some limitations to immunoisuppressive agents, I.E, what limits their use in us?
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
What is PTLD?
Post-Transplant Lymphoproliferative Disorder - a lymphomas or cancer
244
PTLD is strongly associated with what?
being Epstein-Barr negative (a DNA virus)
245
What are some risk factors for PTLD?
presence and intensity of immunosuppressed state primary infection with EBV primary infection with CMV
246
What is the treatment for PTLD?
``` 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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