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PHAR358 > Transplant > Flashcards

Transplant Flashcards

1
Q

What is transplantation?

A

the moving of living cells, tissues or organs from a donor to a recipient, for the purpose of replacing the recipients damaged or absent organ

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2
Q

What are the types of transplants?

A

autograft:
-occurs within a persons body (self to self)
allograft:
-occurs within two people within the same species
xenograft:
-occurs from one species to another

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3
Q

What are the two types of transplant donors?

A

living donors
deceased donor
-neurological determination of death (NDD)
-donation after circulatory death (DCD)

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4
Q

What is the difference between storage of tissues and organs?

A

tissues can be ‘banked’
organs have to be transplanted immediately

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5
Q

What is the survival rate of transplant?

A

varies depending on the organ:
-5 yr survival for kidney is 80% for deceased donor, 90% for living
-5 yr survival for heart transplant is 75%
-5 yr survival for liver transplant is 81%
-5 yr survival for lung transplant in Canada is ~ 66%
a lifesaving procedure for many

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6
Q

What is a huge barrier to transplant?

A

donor shortage

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7
Q

How long is the average time to get a renal transplant in SK?

A

workup - 1 yr
wait - 2 yrs

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8
Q

What is the program that covers medications for renal transplant patients in SK?

A

SAIL
-all main immunosuppressants covered 100%
-also covers dialysis patients

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9
Q

Where do all non-renal solid organ transplants occur for SK patients?

A

out of province
-post-transplant care provided in SK
-liver, lungs, hearts

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10
Q

Does SAIL cover medications for non-renal solid organ transplant patients?

A

not covered by SAIL
-covered by EDS for immunosuppressants

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11
Q

What is the function of the immune system?

A

recognition and protection against infection by infection causing organisms
recognition and destruction of cells with mutations
cause cell injury and destruction to create inflammation and recruit further immune system response

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12
Q

How does recognition occur?

A

proteins produced by ‘non-self’ organism
signaling molecules created when inflammation is present

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13
Q

What is the role of MHC/HLA?

A

distinguishes ‘self’ from ‘non-self’
expressed on surface of APCs

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14
Q

What are examples of APCs?

A

B cells
macrophages
dendritic cells

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15
Q

What is the role of APCs?

A

displays HLA to host T-cells causing antigen-specific T-cell activation

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16
Q

Differentiate between the two types of T-cells.

A

CD4 (helper or Th):
-recognize MHC class II
-stimulate B and T cells
CD8 (cytotoxic or Tc):
-recognize MHC class I
-kill infected cells

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17
Q

What is the role of B-cells?

A

responsible for antibody formation against antigen

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18
Q

What is another name for T-cells? What about B-cells?

A

T-cells: cell-mediated
B-cells: humoral or antibody-mediated

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19
Q

How does a recipient recognize the transplanted graft as self or foreign?

A

based on the reaction of the histocompatibility antigens

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20
Q

Describe histocompatibility antigens.

A

glycoproteins expressed on nucleated cells
major function is to bind peptides and present them at the cell surface for inspection by T-cells of the immune system
are encoded by the MHC genes that are referred to as the HLA in humans

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21
Q

Describe HLA class I.

A

the proteins produced by these genes are present on most nucleated cells & platelets
primary target for T-lymphocyte reactions
-HLA-A, HLA-B, HLA-C

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22
Q

Describe HLA class II.

A

proteins are present on selective immunoreactive cells
-macrophages, monocytes, activated T-cells, dendritic cells, epithelial cells
-HLA-DR, HLA-DP, HLA-DQ

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23
Q

Describe HLA class III.

A

part of complement system, do not play a specific role in graft rejection

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24
Q

What can be said about HLA and genetics?

A

HLA genes are polymorphic and are genetically inherited as a haplotype

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25
Q

Describe step 1 of the T-cell 3 signal model.

A

recognition
APC presents MHC class II antigen to Th through the TCR-CD3 complex
downstream effect = begin to activate calcineurin pathway, also from the calcineurin pathway and the nucleus of the cell begin to generate IL-2

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26
Q

Describe step 2 of the T-cell 3 signal model.

A

activation of T-cells
occurs when co-stimulatory molecules, CD80 and CD86 which are present on the surface of the APCs interact with the co-stimulatory receptor CD-28

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27
Q

Describe signal 3 of the T-cell 3 signal model.

A

IL-2 is released and binds to IL-2 receptor on the T-cell, activating target of rapamycin necessary for cell proliferation

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28
Q

What is the end result of the T-cell 3 signal model?

A

activated, proliferating Th cell capable of recruiting other components of the immune system –> rejection –> destruction of the graft

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29
Q

What can result in a better transplant outcome?

A

HLA match between the donor and recipient

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30
Q

What is the role of B-cells in allograft rejection?

A

traditionally thought to be a T-cell related process, it is now recognized that B-cells play a key role by the production of anti-donor antibodies that bind to allograft
-donor specific antibodies (DSA)
rejection due to B-cell pathophysiology is termed B-cell rejection or humoral rejection

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31
Q

What are the compatibility tests performed for potential transplant patients?

A

PRA (pannel reactive antibody test)
lymphocyte cross-match
ABO blood typing

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32
Q

Describe the PRA.

A

PRA = the % of positive rxns among the total cell panel
-blood sample from the potential recipient is cross-matched with cells from panel of previously typed donors selected to represent as many HLA antigens as possible
high PRA = broad sensitization, does not reflect antibody strength or titer
-many reasons for sensitization

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33
Q

Describe lymphocyte cross-match.

A

directly tests the reactivity between a patients serum and a potential donors ceells
viable lymphocytes are isolated from samples of the donors blood, spleen, or lymph nodes and cross-matched with potential recipient blood to determine whether pre-formed antibodies to donors lymphocytes are present
+ test = presence of cytotoxic IgG antibodies to donor ( + is BAD)

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34
Q

Describe ABO bloodtyping.

A

matching of blood type is critical
transplanting an organ with ABO incompatibility typically results in a hyperacute rejection and destruction of the graft

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35
Q

What are the different types of rejection?

A

hyperacute:
-uncommon, immediate immunological response
acute cellular rejection:
-occurs anytime, mediated by alloreactive T-cells
humoral rejection/antibody mediated rejection:
-antibody mediated process, poorer prognosis
chronic rejection:
-most common cause of late graft loss, no effective tx

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36
Q

Which organ requires the greatest level of immunosuppression?

A

lung > heart, kidneys > liver

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37
Q

What are the immunosuppressive therapy classes?

A

IL2 receptor antagonist
-basiliximab
lymphocyte depleting antibody
-anti-thymocyte globulin
corticosteroid
-prednisone, methylprednisolone
antiproliferatives
-mycophenolic acid derivates, azathioprine
calcineurin inhibitors
-cyclosporine, tacrolimus
M-tor inhibitors
-sirolimus

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38
Q

What are the two phases of immunosuppressive pharmacotherapy?

A

induction therapy
maintenance therapy

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39
Q

When is the risk of acute rejection the highest?

A

the first 1-3 months
-higher doses of immunosuppressants are used during this time

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40
Q

What is induction therapy?

A

treatment with a biologic agent begun at the time of transplant to deplete or modulate T-cell response
induction therapy improves the efficacy of immunosuppression by reducing acute rejection and allowing for the reduction in other maintenance meds

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41
Q

What does the typical induction therapy regimen look like?

A

IL-2 receptor antagonist OR lymphocyte depleting antibody
+ corticosteroid, antiproliferative, and calcineurin inhibitor

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42
Q

What is an example of an IL-2 receptor antagonist?

A

basiliximab

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43
Q

What is the MOA of basiliximab?

A

binds to IL-2 receptors on activated lymphocytes preventing IL-2 binding to the receptor
-humanized, recombinant IgG1 IL-2 receptor MAB

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44
Q

What are the drug interactions of basiliximab?

A

no DI’s

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45
Q

What are the side effects of basiliximab?

A

usually well tolerated
can have acute hypersensitivity

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46
Q

What is an example of lymphocyte depleting antibody?

A

anti-thymocyte globulin (thymoglobulin)

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47
Q

What is the MOA of anti-thymocyte globulin?

A

the antibodies in ATG bind to antigens found on the surface of the surface of T-cells and deplete T-cells from circulation
-polyclonal (recognizes multiple epitopes, broader coverage)

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48
Q

What is the use of anti-thymocyte globulin?

A

induction or rejection (cell mediated)
-more potent = used if higher risk of rejection

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49
Q

What are the side effects of anti-thymocyte globulin?

A

bone marrow suppression
anaphylaxis
hepatic
infusion related reactions (premed to prevent)

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50
Q

What does the typical maintenance immunosuppression regimen look like?

A

cyclosporine or tacrolimus
azathioprine or mycophenolate
corticosteroid
done with the biologic

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51
Q

What is the MOA of corticosteroids?

A

bind to the glucocorticoid receptor, which in turn, up-regulates the expression of anti-inflammatory proteins in the nucleus and represses the expression of proinflammatory proteins in the cytosol by presenting the translocation of other transcription factors from the cytosol into the nucleus
-inhibit antigen proliferation, cytokine production, and proliferation of lymphocytes

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52
Q

How are corticosteroids given in transplant?

A

IV initially
switched to oral prednisone and tapered to the lowest effective dose

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53
Q

What are some side effects of corticosteroids?

A

short-term:
-insomnia, GI, personality changes, glucose alterations
long-term:
-osteoporosis, MSK changes, cataracts

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54
Q

How can osteoporosis and hyperglycemia caused by corticosteroids be managed?

A

osteoporosis:
-routine BMD
-pharmacotherapy (vit D, calcium, bisphosphonates)
hyperglycemia:
-hope it resolves with tapering doses
-diet, oral hypoglycemics, insulin
- ? stop tacro

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55
Q

What is the MOA of azathioprine?

A

purine analog, likely affects purine synthesis & metabolism, suppresses T & B cells (prodrug of 6-mercaptopurine)
-general immunosuppressant

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56
Q

What are the adverse effects of azathioprine?

A

bone marrow suppression
skin lesions
hepatic
pancreatitis
alopecia

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57
Q

What is a key drug interaction with azathioprine?

A

allopurinol
-severe immunosuppression
-best to call and check

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58
Q

Which drug has largely replaced azathioprine?

A

mycophenolic acid derivatives

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59
Q

What is the MOA of mycophenolic acid derivatives?

A

purine analog = affects purine synthesis and metabolism, suppresses T & B cells
-more specific than azathioprine (does not affect other rapidly dividing cells)

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60
Q

What are the two formulations of mycophenolic acid?

A

mycophenolate mofetil
-prodrug converted to MPA via 1st pass
mycophenolate sodium
-deliver active moiety (MPA)
both are oral

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61
Q

How is mycophenolic acid dosed?

A

empiric based on type of organ

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62
Q

Do we gather mycophenolic acid levels?

A

it is possible to do mycophenolic acid levels but they are not routinely done

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63
Q

What are the adverse effects of mycophenolic acid?

A

GI: diarrhea, nausea, indigestion
neutropenia
teratogenic: birth control for males and females

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64
Q

What are the drug interactions of mycophenolic acid?

A

divalent cations (iron, calcium)
cholestyramine, colestipol
food decreases rate but not extent of absorption

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65
Q

How can the GI side effects of mycophenolic acid be managed?

A

rule out infectious causes
administer with food
use of PPI or H2RA
divide total daily dose into 3-4 doses (or decrease if possible)
try alternate formulation
loperamide for diarrhea if non-infectious
consider change to azathioprine if unable to manage

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66
Q

How can neutropenia caused by mycophenolic acid be managed?

A

reduce dose if possible
look for other drug causes and eliminate if possible
-increased risk with valganciclovir
filgrastim/GCSF if needed

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67
Q

What are examples of calcineurin inhibitors?

A

cyclosporine
tacrolimus

68
Q

What is the MOA of calcineurin inhibitors?

A

forms a complex with their cytoplasmic receptor proteins that bind with calcineurin, inhibition of calcineurin impairs the expression of several cytokine genes that promote T-cell activation

69
Q

True or false: cyclosporine and tacrolimus can be combined

A

false

70
Q

What are some important PK parameters of cyclosporine?

A

bioavailability: 60-80%
t1/2: 8h
lipid soluble
extensive PPB (90-98%)
metabolism:
-substrate of 3A4 and P-gp
-weak inhibitor of 3A4, strong inhibitor of P-gp

71
Q

Describe cyclosporine drug level monitoring.

A

can do trough (C0) level or 2h post dose (C2) level
C2 preferably no more than 15 min from the 2h mark
C0 - 11.5-12.5 h after last dose

72
Q

What are the two formulations of tacrolimus?

A

Advagraf and Prograf
-not bioequivalent
-Advagraf is ER for OD dosing
-Prograf is q12h dosing

73
Q

What are important pharmacokinetic parameters for tacrolimus?

A

bioavailability: ~25%
t1/2: 8-11h
bound primarily to albumin (99%)
metabolism via 3A4

74
Q

Describe tacrolimus drug level monitoring.

A

trough level (C0)
timing preferably no more than 30 minutes from the C0 hour mark

75
Q

What are the adverse effects of calcineurin inhibitors?

A

nephrotoxicity - acute and chronic
neurotoxicity - HA, tremor, paresthesia, dizziness, fatigue, szs
hypertension
electrolyte imbalances - increased K, decreased Mg and PO4
GI
hepatotoxicity

76
Q

Where do cyclosporine and tacrolimus differ in side effects?

A

cyclosporine:
-increased BP & lipids, hyperuricemia
-cosmetic effects (hirsutism, acne), gingival hyperplasia
tacrolimus:
-increased HA & GI (esp diarrhea), increased hyperglycemia
-alopecia unique

77
Q

How can we manage the side effects of calcineurin inhibitors?

A

hypertension: CCB, ACEI, ARB, beta-blockers
blood sugar: oral hypoglycemics, insulin
lipids: use lowest dose of statin possible (more muscle AE)

78
Q

What are the drug interactions of calcineurin inhibitors?

A

numerous as metabolized by CYP450 3A4
most common:
-clarithromycin & erythromycin (not azithromycin)
-diltiazem & verapamil
-fluconazole
-rifampin
-grapefruit juice
also: echinacea
PD interactions: nephrotoxic drugs

79
Q

How are the drug interactions of calcineurin inhibitors managed?

A

avoid if possible
dose adjustment and drug level management if cannot be avoided

80
Q

What is an example of an mTor inhibitor?

A

sirolimus

81
Q

What is the MOA of sirolimus?

A

binds to FKBP but does not block calcineurin - engages the TOR which reduces the cytokine-dependent cellular proliferation of the G1-S phase of the cell division cycle
-both hematopoietic and non-hematopoietic cells are affected

82
Q

What are some important pharmacokinetic parameters for sirolimus?

A

poorly absorbed ( F ~15%)
long t1/2: 60 h
extensive binding to PPB (92%)
metabolism: CYP 3A4

83
Q

What are the drug interactions of sirolimus?

A

same as calcineurin inhibitors

84
Q

What are the drug level monitoring parameters for sirolimus?

A

trough level
-range usually 8-15 ug/L

85
Q

When do we use sirolimus?

A

to replace the calcineurin inhibitor
-declining renal function due to calcineurin inhibitors
malignancy (?anti-tumor properties)
potentially (used rarely) an add on therapy for those that need increased immunosuppression
-lung transplant with declining therapy despite TT
maybe someone overly immunosuppressed
-less potent

86
Q

What are the adverse effects of sirolimus?

A

delayed wound healing
hyperlipidemia
arthralgias
anemia, thrombocytopenia
hypertension
rash
mouth sores - idiosyncratic
edema - basement membrane leakage, non responsive to diuretic
proteinuria

87
Q

How can we manage the side effects of sirolimus?

A

hyperlipidemia: treat
anemia: treat, thrombocytopenia (stop?)
hypertension: treat
rash: ? dose related, reduce if possible, d/c if significant and non-resolving
mouth sores: reduce if possible, mouthwashes, stop
edema: reduce dose, d/c CCB, stop
proteinuria: monitor ACR, stop

88
Q

What is the treatment for acute cellular rejection?

A

generally responds well
-high dose steroids
-antibody therapy (anti-thymocyte globulin)

89
Q

What is the treatment of humoral rejection/antibody mediated rejection?

A

less responsive
-plasmapheresis, steroids, anti-thymocyte globulin, IV immune globulin
-rituximab, tocilizumab, bortezomib

90
Q

What is the treatment of chronic rejection?

A

most common cause of late graft loss
no effective treatment
-increase maintenance immunosuppression

91
Q

How frequently do transplant patients need bloodwork?

A

frequency depends on the time post transplant, the clinical status of the patient and the type of organ
at minimum most people will have bloodwork q monthly
-except heart transplants

92
Q

Why do transplant patients need frequent bloodwork?

A

helps monitor for rejection (except hearts) & to monitor for toxicity from immunosuppressive medications

93
Q

What does standard bloodwork consist of for transplant patients?

A

drug levels (CSA, TAC, or SRL)
renal function (SCr, urea)
hematology/CBC
electrolytes (Na, Cl, K, CO2, Mg, PO4)

94
Q

What are the arguments in favor of generic immunosuppressants?

A

significant cost savings/economic benefits
same API and stringent testing required by HC to show BE
widely used in other countries, no evidence to suggest harm
other critical dose drugs are generic

95
Q

What are the arguments against generic immunosuppressants?

A

lack of published evidence in transplant populations
potential for uncontrolled product switching is concern since generic preps are not required to show BE with eachother
switches are likely to occur without prescriber knowledge
generics will lead to more TDM and clinical monitoring and increased patient monitoring will be needed

96
Q

Which organs are possible to transplant from living donation?

A

kidney and liver

97
Q

What are the pros of kidney transplant?

A

no more dialysis
less dietary restrictions
avoid dialysis related complications
improvements in mortality
economics

98
Q

What are the cons of kidney transplant?

A

complicated regimen of immunosuppressant therapy
risks of immunosuppression

99
Q

Who is eligible for a kidney transplant?

A

referral for evaluation usually happens prior to dialysis
generally not listed until GFR < 20 ml/min
pre-emptive transplant possible
some common indications:
-diabetes
-hypertension
-glomerulonephritis
-polycystic kidney disease

100
Q

What does the immunosuppressive regimen look like for kidney transplant patients?

A

in general will follow the previously discussed regimen
-biologic therapy for induction + maintenance TT

101
Q

What are some monitoring parameters for kidney rejection?

A

routine bloodwork including:
-SCr
-urea
-elytes
-drug levels

102
Q

What are the symptoms of kidney rejection?

A

acute:
-abrupt in increase in SCr > 30% baseline
-fever
-decreased urine output
-weight gain
-HTN
-edema
-pain over the kidney
chronic:
-HTN
-proteinuria
-progressive decline in renal function

103
Q

What are some “other” issues with kidney transplant?

A

delayed graft function
-the need for dialysis in the 1st week post transplant
BK virus/polyoma virus
-opportunistic infection which is a major cause of graft loss
-associated with increased levels of immunosuppression

104
Q

Who is eligible for liver transplant?

A

patients with decompensated liver disease
some common indications:
-chronic viral hepatitis C and B
-autoimmune hepatitis
-PBC and PSC
-alcoholic liver disease
-hepatocellular carcinomia
-kids: biliary atresia

105
Q

Describe the immunosuppression needed for a liver transplant.

A

least immunogenic organ
complete steroid weaning is almost always the goal
while induction and TT is used initially, it is often possible to taper this to one agent over time
-steroid usually weaned first
-MPA usually tapered around 1yr

106
Q

What are some monitoring parameters for liver rejection?

A

liver enzymes and routine bloodwork

107
Q

What are the symptoms of liver rejection?

A

acute:
-increased bilirubin and liver enzymes
-leukocytosis
chronic:
-vanishing bile duct syndrome
-increased liver enzymes
-increased bilirubin leading to jaundice
-itching

108
Q

What is a potential issue with liver transplant?

A

recurrence of disease with some conditions

109
Q

Who is eligible for a heart transplant?

A

advanced HF non-responsive to medical therapy but otherwise healthy
common indications:
-cardiomyopathy
-severe CAD with scar tissue
-congenital defects

110
Q

Describe immunosuppression needed for a heart transplant.

A

in general follow the previously discussed regimen
-biologic induction therapy + maintenance TT
IS levels are similar to kidneys but prednisone is eventually often tapered

111
Q

What are the issues with heart transplant?

A

the transplanted heart is denervervated
-increased resting HR (90-110bpm)
-decreasing ability for HR to rise quickly with exercise
-MI may be asymptomatic
-altered response to drugs that work via ANS

112
Q

What do all adult patients with a heart transplant require?

A

statin (regardless of LDL)
ASA
ACEI

113
Q

How can we monitor heart transplants for rejection?

A

no great way to monitor
-labs are not helpful
protocol biopsies are scheduled depending on time post transplant

114
Q

What are the symptoms of heart rejection?

A

acute:
-majority of episodes are asymptomatic
-sx may include fever, malaise, decreased exercise tolerance, hypotension, CHF
chronic:
-coronary graft vasculopathy
-specific pathology unique to transplanted vessels

115
Q

Who is eligible for a lung transplant?

A

healthy younger patients with chronic, end-stage lung disease who are failing maximal medical therapy
common indications:
-cystic fibrosis
-COPD
-pulmonary fibrosis
-pulmonary hypertension

116
Q

What should potential lung transplant patients be able to demonstrate?

A

adequate health behavior and a willingness to adhere to health care guidelines

117
Q

Describe the immunosuppression needed for a lung transplant.

A

high levels of immunosuppressants are necessary to prevent rejection
induction therapy + triple therapy maintenance is almost always necessary (sometimes even quadruple therapy)

118
Q

How can we monitor lung transplants for rejection?

A

routine pulmonary function tests

119
Q

What are the symptoms of lung rejection?

A

acute:
-fever, flu-like, chest pain, cough, SOB, decline pulmonary function tests, +/- weight
chronic:
-termed ‘Chronic Lung Allograft Dysfunction’

120
Q

Which antibiotic is sometimes used in lung transplant patients?

A

azithromycin 250 mg EOD

121
Q

What are some issues with lung transplant?

A

lung transplants have additional susceptibility compared to other organs
factors:
-exposure via direct inhalation
-high IS load
-denervation which inhibits cough reflex
prophylactic medications may be long term

122
Q

What is infection risk related to in transplant patients?

A

overall level of immunosuppression & is generally > in first 3 months post transplant & following tx for acute rejection
pts may not exhibit normal immune responses as in the general population

123
Q

What kind of symptoms need to be taken with caution in transplant patients?

A

pts must report any signs/symptoms of infection
-fever, chills, sore throat, dysuria, skin infections, diarrhea, etc

124
Q

What is the most common opportunistic infection post transplant?

A

CMV (cytomegalovirus)

125
Q

What does the risk for CMV depend on?

A

dependent on donor/recipient serology
- D+R- > D+R+ > D-R-

126
Q

What is the presentation of CMV?

A

viremia (flu-like symptoms, deceased WBC and platelets)
can “enter” organs
-enteritis, pneumonitis, hepatitis, retinitis

127
Q

What is the prophylactic treatment for CMV post transplant?

A

usually valganciclovir x 100-200 days or screening with CMV PCR and pre-emptive treatment

128
Q

What is the treatment for active CMV?

A

IV ganciclovir, po valganciclovir
?CMV immunoglobulin as an adjunct
?letermovir ?maribavir

129
Q

What is the prophylactic treatment for PJP post transplant?

A

co-trimoxazole x 6-12 months
-perhaps indefinitely in lungs

130
Q

What is Epstein Barr virus a major cause of post transplant?

A

post transplant hypoproliferative disorder
-type of cancer

131
Q

When do we do prophylaxis or monitoring for Epstein Barr in transplant patients?

A

D+R-

132
Q

What is polyoma BK virus associated with?

A

nephropathy and graft loss

133
Q

How does malignancy risk differ between transplant patients and the general population?

A

transplant patients have 3-4 x risk than general pop
-skin, cervical & anorectal, lymphoma, PTLD

134
Q

What should be encouraged for regarding transplant patients and malignancy risk?

A

routine screening & lifestyle factors
-protect from sun/sunscreen
-regular pap & colonoscopy
-regular dermatologic exams

135
Q

Describe PTLD.

A

diverse spectrum of disease with varied clinical presentation
-may be nodal/extranodal, may localize in allograft or be disseminated; may be indistinguishable from non-Hodgkins lymphoma
highest risk in pediatrics
monitoring = EBV load

136
Q

What is the treatment for PTLD?

A

decrease immunosuppression
rituximab??

137
Q

What is a common metabolic complication of transplant?

A

osteoporosis/osteopenia

138
Q

Describe osteoporosis/osteopenia in transplant.

A

regular BMD monitoring
optimize vitamin D & calcium
targeted treatment for high risk patients (i.e. bisphosphonates)

139
Q

What is a fairly routine supportive therapy seen in transplant patients?

A

H2RA or PPI for dyspepsia or GI AEs of IS
-PPI prophylaxis is routine in many centers

140
Q

How does immunosuppressive therapy contribute to GI effects?

A

MPA associated with increased GI AEs
TAC > CSA
SRL - mouth ulcers
steroids - ulcerogenic

141
Q

What is a major cause of morbidity and mortality in transplant patients?

A

cardiovascular disease

142
Q

What is the use of the Framingham risk score in transplant patients?

A

underestimates risk

143
Q

What is key regarding CV risk factors and transplant patients?

A

try decrease risk factors
-BP, DM, smoking, weight, lipids

144
Q

How does immunosuppressive therapy contribute to hyperlipidemia?

A

SRL > CSA, TAC

145
Q

What is 1st line for hyperlipidemia in transplant patients?

A

statins
-remember increased risk of myopathy/rhabdo
-start at 1/2 dose & titrate pending effect & tolerance

146
Q

Which lipid drug can increase levels of calcineurin inhibitors?

A

ezetimibe

147
Q

How common is hypertension in transplant patients?

A

50-90% of kidney & liver and almost all hearts

148
Q

How does immunosuppressive therapy contribute to hypertension in transplant patients?

A

CSA and TAC contribute to HTN

149
Q

What is the BP target for transplant patients?

A

optimal target unknown
extract from general population and tx to high risk (130/80?)

150
Q

Describe hypertension treatment in transplant patients.

A

ACEI/ARB:
-may affect renal function
CCB:
-increase CNI levels (diltiazem and verapamil)
-contribute to peripheral edema & gingival hyperplasia
diuretics:
-decreased renal function if hypovolemic
-decrease K and increase uric acid
avoid aliskiren (5x AUC in combo with CSA)

151
Q

How does immunosuppressive therapy contribute to anemia in transplant patients?

A

MPA and SRL contribute to anemia

152
Q

What is the treatment for anemia in transplant patients?

A

may require iron, erythropoietin or darbepoietin
treat bc anemia may contribute to CVD

153
Q

How common is renal insufficiency as a complication of transplant?

A

complication of all solid organ transplant
CKD affects 30-50% of non-renal transplants

154
Q

How is renal insufficiency managed in transplant patients?

A

modify medications/procedures to minimize renal AEs

155
Q

What is the risk of diabetes in transplant patients?

A

increased risk for CVD, decreased graft function & survival
worsening of existing diabetes

156
Q

How does immunosuppressive therapy contribute to new onset diabetes in transplant patients?

A

CNIs contribute ( TAC > CSA)
steroids contribute

157
Q

What is the treatment for new onset diabetes in transplant patients?

A

may require oral hypoglycemics or insulin

158
Q

How does immunosuppressive therapy contribute to gout in transplant patients?

A

CSA > TAC

159
Q

Describe gout treatment in transplant patients.

A

generally do not treat asymptomatic hyperuricemia
avoid NSAIDs
counsel on diet
may use steroids, colchicine or allopurinol
-dose adjust based on renal fxn & manufacturer recommendations

160
Q

What are some common electrolyte disturbances in transplant patients?

A

decreased Mg
decreased PO4
increased K
increased Ca

161
Q

How are electrolyte disturbances managed in transplant patients?

A

oral or IV supplementation
correct underlying cause if possible

162
Q

What are some important considerations with transplant and pregnancy?

A

pregnancy should NOT be considered without consultation from transplanting center
pregnancy may pose risk to mother and organ
improved health post transplant may lead to return to fertility

163
Q

Describe appropriate immunization recommendations in transplant patients.

A

no live vaccines
vaccine response post transplant is often blunted
influenza yearly recommended for all patients

164
Q

Describe appropriate precautions to take with drug interactions in transplant patients.

A

there are many!
always check, consider expected as well as reported
avoid NSAIDs and other nephrotoxins
if unsure, double check with transplant center
generally avoid herbals
-anything that stimulates the immune system is a problem

165
Q

What is a common cause of graft loss?

A

non-adherence
-adolescent population is high risk

PHAR358 (18 decks)

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