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Therapeutics 358 Final > Transplant > Flashcards

Transplant Flashcards

1
Q

Define transplantation

A

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

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2
Q

Describe the different body parts of transplant that can occur. Examples:

A

Organs:
Kidneys, heart, liver, lungs, pancreas, intestine, thymus

Tissues:
Bones, tendons, corneas, skin, heart valves and veins

Cells:
Stem cells, islet cells

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3
Q

Do transplants last forever? Can more than one organ be transplanted?

A

No

Transpplants doo not last forever

Can be multi-organ – common situation is to hae one organ

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4
Q

What are the different types of transplant that can occur?

A

Autograft

Allograft

Xenograft

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5
Q

Define autograft

A

Transplant that occurs within body (self to self) – skin graft, CABG (potentially)

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6
Q

Define Allograft

A

Transplant within two people within the same species (Twins)

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7
Q

Define xenograft

A

Transplant from one species to another ( Experiemental; working on this for decades, pig heart and kidney transplant)

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8
Q

Define the types of donor for a transplant

A

Living donor – Can donate one kidney, donate piece of liver

Deceased donor
Neurological determination of death (NDD)
Donation after circulatory death (DCD)

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9
Q

Are tissues for transplant immediately transplanted? Organs?

A

Tissues may be ‘banked’, however organs must be transplanted immediately, which poses surgical and geographic challenges

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10
Q

Transplants are considered a _______ procedure

A

Life-saving procedure for many

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11
Q

Describe the survival rates of various types of transplant

A

Lung Lowest 5 year survival rate

Survival rate varies depending on the type of transplant

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12
Q

Describe transplant of kidneys regarding duration and choice for patient

A

Kidneys

Dialysis; so there is a choice here

Kidney transplant –> 12-15 years – if have one really young, may need another one when you are older

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13
Q

Describe why lungs have the lowest survival rate out of all transplants

A

Lungs are finnicky: require more immunosuppression, contribute to more toxicities and rejections

Lungs are exposed to the external environment all day long so less barrier

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14
Q

What is the major barrier to transplant? How many Canadians are on the waitlist for a transplant?

A

Donor shortage is a huge barrier

~ 3500 Canadians are on the waitlist for organ transplant

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15
Q

Describe how organ sharing occurs in Canada?

A

Different centres across the country

Organ sharing occurs locally first, then if not a match to someone in SK, national sharing as well

Highly Sensitize Registry: Anytime an organ becomes available, scanned against everyone else to have the best chance of getting it

Healthcare is provincial so difference: Wait times may be different across the country

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16
Q

What is the most common type of transplant?

A

Kidney

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17
Q

Describe the average time for renal transplant in SK?

A

Average time:
workup – 1yr
wait – 2yrs

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18
Q

Describe a program in Sk for renal transplant reciepients

A

Medications covered under SAIL

Saskatoon Aid for Independent Living:

  • program in sask that covers specific people; covers a lot of dialysis patients in SK (renal replacement therapy – transplant meets this criteria),

Immunosuppressive covered 100%, cover adjunctive meds as well

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19
Q

Describe where other organ transplants occur in Canada?

A

Transplanted out of province (usually Edmonton, occasionally Winnipeg)

Post-transplant care provided in SK

Livers, lungs, hearts
Adults, pediatrics

Medication coverage differences – not covered by SAIL; EDS: coverage same as every one else

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20
Q

Describe the function (s) of the immune system?

A

Recognition and protection against infection by infection causing organisms

Recognition and destruction of cells with mutations (e.g. cancer cells)

Cause cell injury and destruction to create inflammation and recruit further immune system response

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21
Q

How does recognition occur in the immune system?

A

Proteins produced by ’non-self’ organism

Signaling molecules created when inflammation is present

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22
Q

List the components of the immune system

A

Major histocompatibility complex (MHC)/Human leukocyte antigens (HLA)

Antigen presenting cells (APC)

T lymphocytes “cell-mediated”

B lymphocytes “Humoral” or “antibody-mediated”

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23
Q

Describe the role of the MHC/HLA. Where is it located?

A

Distinguishes ‘self’ from ‘non-self’
Expressed on surface of antigen presenting cells

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24
Q

Describe the role of APC

A

B cells, macrophages, dendritic cells

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

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25
Q

Describe the role of T lymphocytes

A

T lymphocytes “cell-mediated”

CD4 (“Helper” or :TH”)
Recognize MHC class II
Stimulate B- and T-cells

CD8 (“Cytotoxic” or “Tc”)
Recognize MHC class 1
Kill infected cells

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26
Q

Describe B-lymphocytes

A

B lymphocytes “Humoral” or “antibody-mediated”
Responsible for antibody formation against antigen

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27
Q

Describe the role of MHC in the reciepient of the transplant

A

The recipient recognizes the the transplanted graft either as self or foreign based on the reaction to histocompatibility antigens

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28
Q

Describe histocompatability antigens and their role in the immune system

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 major histocompatibility complex (MHC) genes that are referred to as the Human leukocyte antigen (HLA) in humans

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29
Q

What is the most important Hiscompatbility antigen? Describe its role in transplant?

A

HLA matching here
HLA is the version of the MHC found in humans: HLA more specific as only found in humans

HLA: Most important antigens responsible for graft rejection

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30
Q

Describe the different HLA Classes

A

200 Genes located on chromosome 6

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31
Q

Describe the inheritance of HLA genes?

A

HLA genes are polymorphic and are genetically inherited as a haplotype (groups)

HLA alleles are polymorphic and are designated by a number (ie HLA –A1 or HLA-A2)

HLA-A identical: Perfect match (share all the same alleles)

Siblings: 25% the same alleles, 25% chance no same alleles, 50% chance of mixed alleles

Even though may have perfect allele match, other antigens (minor histocompability antigens) can provoke rejection

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32
Q

Describe the T-cell signal Model

A

Drugs that work differenytly: Wider coverage, prevent toxicity – use lower doses of each in combo (like acet and iBu hehe)

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33
Q

Describe the overall role of HLA-typing

A

In general, the closer the HLA match between the donor and the recipient, the better the outcome

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34
Q

Describe the role of B cells in transplant

A

Although allograft rejection was 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 allografts (termed Donor Specific Antibodies or DSA)

Rejection due to B-cell pathophysiology is termed B cell rejection or Humoral rejection

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35
Q

List the different types of compatability tests used for transplant

A

PRA (pannel reactive antibody test)

Lymphocyte cross-match

ABO blood typing

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36
Q

Describe PRA compability test

A

PRA (pannel reactive antibody test)

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.

PRA or panel reactive antibody = the percentage of positive reactions among the total cell panel.

A high PRA indicates broad sensitization, but it does not reflect antibody strength or titer.

Many reasons for sensitization, eg transfusions, transplants, pregnancies

Measure of sensitization

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37
Q

Describe an example of PRA compability tests

A

Tony crossed with a sample of many people: percentage of reactions Tony has to the sample

Tony: 88% - Reacting to 88% of people
Higher PRA: more sensitization: Not a good thing

Highly sensitized against panel cells: less chance of Tony getting a kidney

PRA: General measure of sensitization, does not represent antibody strength or titre
PRA: 99% -> Go on highly sensitized registry

Scanned across canada get organ: 1 in a million organ

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38
Q

Describe lymphocyte cross-match compatability testing

A

Directly tests the reactivity between a patient’s serum and a potential donor’s cells

Viable lymphocytes are isolated from samples of the donor’s blood, spleen or lymph nodes cross-matched with potential recipient blood to determine whether pre-formed antibodies to donor’s lymphocytes are present

+ test indicates the presence of cytotoxic IgG antibodies to the donor (+ is BAD!)

Virtual crossmatch

Not a contraindicatication with liver: More tolerogenic organ

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39
Q

Describe antibody testing timing prior to transplant

A

Antibody levels fluctuate, therefore tests are done continuously while the potential recipient is waiting for a transplant

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40
Q

Describe ABO blood typing

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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41
Q

When is ABO blood typing not required in a transplant?

A

Exceptions to this rule  In pediatric herat transplants, can transplant a cross blood type  Not an issue if less than one

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42
Q

Describe the role of immunosupression for organ transplantation

A

A complex regimen of medications is needed to prevent the recipient’s immune system from rejecting the new organ

Immunosuppressive regimens consist of drugs that work at different levels of the immune cascade

The amount of immunosuppression required will vary depending on the organ transplanted
(in general, lung> heart, kidney> liver)

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43
Q

Describe other factors that play a role in the immunosupression for organ trasnaplantation:

A

Many other factors also play a role, including:

Match between donor and recipient

Time post-transplant
- Immune system high post-transplant; increased risk of rejection, require induction therapy and decrease drugs over time

Underlying disease
- If reason for transplant is immunoreactive disease, need higher immunosupression

Patient history

Medication tolerance

Patient age, race
- Men aged 18-30 and African AMericans have more robust immune system

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44
Q

Descibe the diferrent types of rejection

A

Hyperacute
Acute Cellular Rejection (ACR)
Humoral Rejection/Antibody Mediated rejection
Chronic rejection

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45
Q

Describe hyperacute rejection

A

Uncommon, immediate immunological response

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46
Q

Describe acute cellular rejection

A

Occurs anytime
Mediated by alloreactive T lymphocytes

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47
Q

Describe humoral rejection/antibody mediated rejection

A

Humoral rejection/Antibody mediated rejection – ‘vascular rejection’
Antibody mediated process
Poorer prognosis

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48
Q

Define chronic rejection

A

most common cause of late graft loss
No effective treatment
(slow gradual decline/ process)

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49
Q

Describe the immunosupressive therapies (list) that can be used in transplant

A
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50
Q

Describe the approach to medication therapy in transplant

A

Multidrug approach utilized

2 phases:

1) INDUCTION THERAPY
- Risk of acute rejection is highest in first 1-3 months

2) MAINTENACE THERAPY

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51
Q

Why is induction therapy required?

A

The risk of acute rejection is highest in the first 1-3 months, so higher doses of immunosuppressants are used during this time

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52
Q

How does induction therapy occur?

A

Induction therapy is treatment with a biologic agent begun at the time of transplant to deplete or modulate t-cell response (done in hospital)

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53
Q

Describe the effect of induction therapy

A

Induction therapy improves the efficacy of immunosuppression by reducing acute rejection and allowing for the reduction in other maintenance medications

Gives us broad coverahe for. A short period of time

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54
Q

Describe the medication(s) used for induction therapy

A
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55
Q

Describe Basiliximab (Simulect): MOA, Dose, D.I.

A

Humanized, recombinant IgG1 interleukin-2 receptor monoclonal antibody

MOA: Binds to IL-2 receptor on activated lymphocytes preventing IL-2 binding to the receptor – prevents cellular proliferation – maintained for 4-6 weeks

No DIs, usually well tolerated, can have acute hypersensitivity (rare)

Usual Dose: 20mg IV pre-transplant, and again on Day 4 or 5
- Standard dose to everyone – not weight based dose

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56
Q

Describe anti-thymocyte Globulin (ATG, thymoglobulin) MOA, S/E, Dose

A

Polyclonal antibody

MOA: The antibodies in ATG bind to antigens found of the surface of t-cells and depletes t-cells from circulation

For induction or rejection (cell mediated)

SE: bone marrow suppression, anaphylaxis, hepatic, infusion related reactions (premed to help prevent this)
- Count the lifetime doses for rejection and induction: Incraese side ffects, increased risk of cancers, infection

Dose: 1-1.5mg/kg (ABW) daily (x3-10days)
- Weight based dosing (IV)

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57
Q

Describe maintenace immunkosupressive regimens

A
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58
Q

Prednisone MOA, Dosing

A

MOA:

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 presentation, cytokine production, and proliferation of lymphocytes.

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

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59
Q

Adverse EFfects of CS’s

A

Insomnia
Personality changes
Adrenal suppression
Acne, moon facies, bruising, hirsutism
Gastrointestinal
Glucose alterations
Hyperlipidemia/accelerated athersclerosis
Impaired wound healing
Infection
Musculoskeletal changes
Osteoporosis
Pancreatitis
Cataracts, glaucoma

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60
Q

Describe teh short term and long term side effects of CS

A

Short term effects e.g.
Insomnia
Personality changes
Gastrointestinal
Glucose alterations

Long term effects e.g.
Musculoskeletal changes
Osteoporosis
Cataracts

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61
Q

How can osteoporosis of CS be managed?

A

Routine bone density measurements
Pharmacotherapy to prevent or treat osteoporosis
Calcium, Vitamin D
bisphosphonates

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62
Q

How can hyperglycmeia of CS be managed?

A

hope it resolves with tapering doses
diet, oral hypoglycemics, insulin if needed,
?stop tacro?

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63
Q

Describe aziathioprine (AZA) MOA, DOSE

A

MOA: Purine analog, likely affects purine synthesis & metabolism, suppresses T & B cells (Pro-drug of 6-mercaptopurine)

Dose: ranging from 25-150mg once daily

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64
Q

Describe the adverse effects of azathioprine. Drug Inetraction(s)?

A

Adverse effects:
bone marrow suppression
skin lesions
hepatic
pancreatitis,
alopecia, etc…..

Drug interactions: remember Allopurinol

Largely replaced by Mycophenolic acid derivatives

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65
Q

Describe the drug interaction between Aziathioprine and ALoopurinol

A

Allopurinol: Gout (used in gout) – quite common in transplant patients
Can cause myelosuppression –>Severe

Call in check or see if transplant centre: Can be used together but need to adjust doses

Allopurinil inhibites glutathione-S-transferase: Incraeses plamsa levels of 6-mercaptopurine

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66
Q

Describe 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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67
Q

Describe the formulations of mycophenolic acid derivatives

A

Formulations: (both oral)

Mycophenolate mofetil (MMF) (Cellcept®)
Prodrug: rapidly converted to mycophenolic acid (MPA) via first pass metobolism
IV form also available

Mycophenolate sodium (EC-MPS) (Myfortic®)
Enteric coated tablets , deliver active moiety (MPA)

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68
Q

Dosing of Mycopheolic ACid Derivatives

A

Dosing: Empiric, Based on type of organ (q12)
Standard dose: Cellcept 1g bid =Myfortic 720mg bid (kidney)

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

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69
Q

Adverse EFfects of Mycophenolic Acid Derivatives

A

Adverse effects:
GI: diarrhea, nausea, indigestion (MAJOR)
Neutropenia - Must monitor WBC count in individuals who have received a transplant

Teratogenic: birth control for males and females

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70
Q

Describe the drug inetractions of Mycophenolic ACid Derivatives

A

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

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71
Q

Describe how the GI side effects of Mycophenolic acid can be managed

A

Food may decrease absorption

Adherence is extremely important

Will still space with medications to twice a day

  • often say take with food to help alleviate GI side effects

Do a lot of counselling on this front here as can be confusing for the patient

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72
Q

How can the GI adverse effects of mycophenolic acid be managed? (more in depth here)

A

rule out infectious cause

administer with food

Use of acid suppressive medications (PPI, H2RA)

divide total daily dose into 3 or 4 doses (or decraese if possible)

try alternate formulation (ie, Cellcept to Myfortic)

loperamide for diarrhea if non-infectious

consider change to azathioprine if unable to manage

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73
Q

How cxan neutropenia due to mycophenolic acid be managed?

A

reduce dose if possible (not always the case).
look for other drug causes and eliminate if possible (incraesed risk when given concurrently with valganciclovir)
Filgrastim/GCSF if needed

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74
Q

What are the two calcicneurin inhibitors?

A

Tacrolimus and cylosporine

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75
Q

Calcineurin Inhibitors MOA. CAn they be userd tohgetehr?

A

Forms a complex with their cytoplasmic receptor proteins (cyclophilin) that binds with calcineurin. Inhibition of calcineurin impairs the expression of several cytokine genes that promote T-cell activation

Cyclosporine & tacrolimus should not be prescribed concurrently

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76
Q

Describe cyclosporine formulation

A

Cyclosporine (NeoralR) supplied at 10, 25, 50, 100mg capsules. Should stay in the foil package prior to administration.
Q12h dosing
Suspension available, IV available (conversion iv:po = 1:3)

77
Q

Pharamcokinetics of cyclosporine

A

Bioavailbility: ~ 60-80%, t1/2 (mean) 8h
Lipid soluble
Extensive binding to plasma proteins (90-98%)
Metabolism –cyp3A4 and pgp

78
Q

Cyclosporine Drug Levels

A

Drug Levels:

can do trough (C0) level or 2 hour post dose (C2) level.

C2 preferably no more than 15 minutes from the 2 hour mark. C0 – 11.5-12.5 hours after last dose.

Level range is dependent on various patient factors such as time since transplant, match, side effects, history, organ

Earlier on: More immunosuprression; higher levels and then overtime we will decrease

Levels are patient specific

79
Q

When is the certain timing of cyclosporine levels preferred for specific transplants?

A

C2 correlated better with AUC  Standard practice  Kidney and live r

CO  Heart and lUngs

80
Q

Describe the different formulations of tacrolimus

A

AdvagrafR and PrografR are NOT bioequivalent

AdvagrafR is an extended-release product intended for once daily dosing, while PrografR is intended for q12h dosing

Both are available in the SAME strengths (0.5,1, 5mg)

EnvarsusR (new) prolonged release formulation; also dosed once daily

IV available (approximately 25% of po Prograf dose)

81
Q

PK of tacrolimus

A

Bioavailability: ~ 25%; t1/2 (mean) 8 -11h
Bound primarily to albumin(99%)
Metabolism – cyp3A4

82
Q

Describe the differences between the different formualtions of tacrolimus

A
  • Advagraf : OD
  • prpgraf : BID
  • equivalency: Under dose by 50%

Envarsus: OD –> Samller dose; less variability in peak to trough ratio

Prograf to Advagraf: adherence: If miss the dose, missing whole day dose

83
Q

Drug Levels of Tacrolimus

A

Trough level only (C0)

Timing preferably no more than 30minutes from the CO hour mark.

Level range is dependent on various patient factors such as time since transplant, match, side effects, history, organ

Ex kidney
New transplant: >10ug/L; after 1 year ? 6-9 ug/L

84
Q

Adverse Effects of Calcineurin Inhibitors

A
85
Q

Describe the difference in potency between TAC and Cyclosporine

A

Tacrolimus is more potent; stronger

Mainly use tacrolimus now; cyclosporine sometimes

86
Q

What is a warning sign of calcineurin toxicity?

A

Headache  Warning sign, go get level checked as can be that level if too high (dose-dependent)

87
Q

Describe the differences in adverse effects of cyclosporine and tacrolimus

A
88
Q

How can HTN cause by calcineurin inhibitors be managed?

A

CCB, ACEIs, ARBs, B blockers….

89
Q

How can blood sugar increases by calcineurin inhibiotrs be managed?

A

oral hypoglycemics, insulin

90
Q

How can increased lipids by calcineurin inhbitors be managed?

A

statins – use lowest dose possible, monitor liver enzymes, creatinine kinase, patient (? Seem to experience muscle aches/weakness frequently)

– drug int., start low and monitor (still appropriate to do so)

atorvastatin, pravastatin, simvastatin, rosuvastatin?

91
Q

Cyclosporine and Tacrolimus Drug Interactions

A
92
Q

Describe MOA of Sirolimus

A

mTor Inhibitor

Macrolide Antibiotic structurally related to tacrolimus

MOA:
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.

93
Q

Formulation of Sirolimus

A

Supplied as 1mg tablets

Available as a liquid that requires refrigeration

Mix dose with 60ml water or OJ. Stir vigorously and drink immediately. Rinse container, stir and drink. Mix in hard plastic or glass cup. Protect from light

94
Q

Sirolimus PK

A

Poorly absorbed (F ~ 15%); Long t1/2 (60 h)
Extensive binding to plasma proteins (92%)
Metabolism –cyp3A4 *Drug interactions = SAME AS Calceurin Inhibitors

95
Q

Drug Monitoring Sirolimus

A

Trough levels (Range: usually 8-15 ug/L)

96
Q

When is sirolimus used?

A

To replace the calcineurin inhibitor (Declining renal function due to calcineurin inhibitors) - Does not have nephrotoxicity

Malignancy (?anti-tumor properties)

Potentially (used rarely) an add on therapy for those that need increased immunosuppression (lung transplants with declining therapy despite triple therapy)

97
Q

Sirolimus Adverse Effects

A
98
Q

How can hyperlipiemia of Sirolimus be managed?

A

Hyperlipidemia: most will need treatment

99
Q

How can anemia of sirolimus be managed?

A

Anemia: treat, thrombocytopenia (stop?)

100
Q

How can HTN of sirolimus be managed?

A

Hypertension: treat as previous

101
Q

How can rash of sirolimus be managed?

A

Rash: ?dose related, reduce if possible, if significant and non-resolving stop drug

102
Q

How can mouth sores of sirolimus be managed?

A

Mouth sores: reduce dose if possible, various mouthwashes, stop drug

103
Q

How can peripheral edema of sirolimus be managed?

A

Peripheral edema: reduce dose, d/c calcium channel blocker if on, stop drug

104
Q

How can proteinuria of sirolimus be managed?

A

Proteinuria: monitor albumin/Creatinine ratio, stop drug

105
Q

How can acute ceelular rejection be treated?

A

Generally responds well

High dose steroids (ex methylpred 500-1000mg iv od x 3 d)

Antibody therapy (anti-thymocyte globulin)

106
Q

How can humoral rejection/antibody mediated rejection be treated?

A

Less responsive

Plasmapheresis, corticosteroids, anti-thymocyte globulin, IV immune globulin

Rituximab
chimeric monoclonal antibody directed against CD20 antigen on B lymphocytes

Tocilizumab, Bortezomib

107
Q

How can chronic rejection be treated?

A

Most common cause of late graft loss, no effective treatment

Increase maintenance immunosuppression

Try your best; post-pone as long as possible

108
Q

Describe blood work requirement in transplant

A

All patients are required to have bloodwork for life!

The frequency will depend 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 (exception heart transplants)

Bloodwork helps us to monitor for rejection (exception hearts) & to monitor for toxicity from immunosuppressive medications

109
Q

Describe what may be included in blood work for an individual who recieved a transplant

A
110
Q

Arguments in favour for generic immunosupressants

A

Significant cost savings/economic benefits

Same active ingredient and stringent testing required by Heath Canada to show bioequivalence

Generic immunosuppressants have been used widely in other countries and to date there is no evidence to suggest harm

Other critical dose drugs are generic (eg, warfarin, digoxin)

111
Q

Aruguments against the use of generics in transplant

A

Lack of published evidence in transplant populations (bioequivalency studies are performed in healthy patients)

The potential for uncontrolled product switching is a concern, since generic preparations are not required to demonstrate bioequivalence with each other.

Switches are likely to occur without prescriber knowledge.

Generics will lead to more therapeutic drug and clinical monitoring, and increased patient education will be needed.

112
Q

What transplants is live donation possible for?

A

With kidney and liver transplants living donation is possible

113
Q

What is teh difference in pharamcotherapy between the types of transplant?

A

Same immunosuppressant drugs used, same principles.

Differences in outcomes, monitoring, immunosuppressant regimens, etc.

114
Q

What are some of the pros and cons of a kidney transplant?

A
115
Q

Who is elegible for a kidney transplant?

A
116
Q

What are some common indications for. akidney transplant?

A

Diabetes
Hypertension
Glomerulonephritis
Polycystic kidney disease

117
Q

Describe the outcomes of kidney transplnat? KP?

A
118
Q

Immunosupression Regimen in KIdney

A

In general kidney transplants will follow the previously discussed regimen

(biologic therapy for induction + maintenance triple therapy

119
Q

What can occur after a kidney transplant is indicative of good prognosis?

A

Copious amounts of urine is a good sign after a kidney transplant

120
Q

How can monitoring for rejection occur in a kidney transplant?

A

Routine bloodwork including SCr, urea, lytes, drug levels can help us to monitor for rejection

121
Q

What are some of the symptoms that indicate rejection in kidney transplant?

A
122
Q

WHat are some other cocnerns in a kidney transplant?

A

Delayed Graft Function

BK Virus/Polyoma Virus

123
Q

Describe delayed graft function in kidney transplant

A

The need for dialysis in the first week post transplant

Original cause of renal failure can be an issue

DGF – has transplant, no pee

Diaysis to kick stsrat things

10-50% of people – slower return to function

124
Q

Describe BK virus/polyoma virus in kidney transplant

A

Opportunistic infection which is a major cause of graft loss

Associated with increased levels of immunosuppression

125
Q

Who is eleigible for a liver transplant?

A

Patients with advanced disease with impaired, non-reversible liver disease (decompensated)

126
Q

What are some of the common inidcations for a liver transplant?

A

chronic viral hepatitis C and B
autoimmune hepatitis
primary biliary cirrhosis (PBC)
primary sclerosing cholangitis (PSC)
alcoholic liver disease
Hepatocellular carcinoma
Kids: biliary atresia

127
Q

Outcome of Liver transplant

A

5-year survival for a liver is roughly 82-87%

128
Q

Immunosupression Regimen in Liver transplant

A

The liver is the least immunogenic organ

Complete steroid weaning is almost always the goal

While induction and triple therapy is used initially, it is often possible to taper this to one agent over time (ex TAC)

Steroid usually weaned first

Mycophenolic acid derivative usually tapered around 1 year

Tacrolimus only and then get the levels down

129
Q

Monitoring of liver transplant

A

Routine bloodwork including including liver enzyme tests can help us monitor for rejection (ALP, AST, ALP, GGT)

130
Q

rejection Sx in Liver transplant

A
131
Q

What is another issue in liver transplant?

A

Recurrence of disease is possible with some conditions

Ex Hepatitis B&C, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis

132
Q

Who is eleigible for a heart transplant?

A

Advanced heart failure, non-responsive to medical therapy, but otherwise healthy

133
Q

Common Indication for Heart Transplant

A

Cardiomyopathy
Severe coronary artery disease with scar tissue
Congenital defects

134
Q

Heart Transplant O8uctome

A

5-year survival for a heart transplant is around 75%

135
Q

Immunosupression in heart transplant

A

In general heart transplants will follow the previously discussed regimen

(biologic therapy for induction + maintenance triple therapy)

IS levels are similar to kidneys but prednisone is eventually often tapered

136
Q

Issues with heart transplant

A

The transplanted heart is denervervated

Increased resting heart rate (90-110bpm), decreasing ability to rise quickly with exercise

MI may be asymptomatic

Altered response to drugs that work via the autonomic nervous system

Not able to recognize rejection symptoms

137
Q

Additional Drugs in a Heart TRansplant

A

All adult patients should receive a statin, (regardless of LDL) to prevent CVD, plus ASA & ACE inhibitor for cardioprotection

138
Q

Monitoring of Heart Transplant for Rejection

A

No great way to monitor! Labs are not helpful

Protocol biopsies are scheduled depending on the time post transplant (no marker to check)

139
Q

Heart Transplant rejection Sx

A
140
Q

Eligibility of Lung Transplant

A

healthy younger patients with chronic, end-stage lung disease who are failing maximal medical therapy.

Potential candidates should be well informed and demonstrate adequate health behavior and a willingness to adhere to health care guidelines

141
Q

Indications of lung transplant

A

Cystic fibrosis
COPD
Pulmonary fibrosis
Pulmonary hypertension

142
Q

Outcome Lung Transplant

A

5-year survival for a lung transplant in Canada is roughly 65%

143
Q

Immunosupression Regimen 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 used - sirolimus)

144
Q

Lung Transplant Monitoring

A

Routine pulmonary function tests can help us to monitor for rejection, bloodwork can help us monitor for toxicity

145
Q

Rejection Sx Lung TRansplant. Tx?

A
146
Q

Other issues of lung tranplant. Risk factors and Tx?

A
147
Q

Describe infection in transplant patients

A
148
Q

Describe the treatmen tof infections in transplant? Sx?

A
149
Q

What are some of the infections of concern in transplant?

A

1) CMV (cytomegalovirus)
2) Pneumocyitis Jiroveci pneumonia (PJP)
3) Herpes Simplex Reactivation
4) Epstein Barr Virus
5) Fungal
6) Polyoma BK Virus (Kidney)

150
Q

How can CMV be manged categories?

A

Prophylaxis
Treatment

151
Q

What is the prophylaxis of CMV?

A

Usually valganciclovir 900mg od x 100-200 days, or screening with CMV PCR and pre-emptive treatment

152
Q

Treatment of CMV

A

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

153
Q

What is the prophylaxis of PJP?

A

Prophylaxis with co-trimoxazole x 6-12 months (perhaps indefinitely in lungs)

Various dosing regimens (ie SMX-TMP 400/80mg od or 800/160mg 3x week)

Options for sulfa allergies – Dapsone, Aerosolized pentamidine

154
Q

What is CMV?

A

Most common opportunistic infection post transplant

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

Oppurtunistic Infections – suppress immune system these come up

Test for prior to the transplant

Most risky with Donor positive, and Recipient has not been exposed

155
Q

Describe the presentation of CMV?

A
156
Q

What is Epstein Barr Virus?

A

A major cause of post transplant hypoproliferative disorder (PTLD)

Prophylaxis or monitoring is common for D+R-

More monitoring in pediatrics as likely to not be exposed to the virus

157
Q

What type of fungal infections can occur with transplant?

A

Candida, aspergillus

158
Q

What is polyoma BK virus?

A

-Associated with nephropathy and graft loss

159
Q

Describe maliganncy after transplant

A

Increased risk (3-4x general population)
Skin, cervical & anorectal cancer, lymphoma, PTLD (post transplant lymphoproliferative disorder)

160
Q

Prevention of maliganncy after transplant

A

Encourage routine screening & lifestyle factors:
Protect from Sun/Sunscreen
Regular pap & colonoscopy
Regular dermatologic exams

161
Q

What is PTLD?

A

PTLD = Post-transplant lymphoproliferative disorder

162
Q

Describe Post-transplant lymphoproliferative disorder

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-Hodgkin’s lymphoma
Highest risk in pediatrics
Monitoring = EBV viral load

163
Q

Tx of PTLD

A

Decrease immunosuppression, rituximab??

164
Q

Describe osteoporosis/osteopenia after transplant

A

a metabolic complication of transplantation
Regular bone densities
Optimize Vitamin D& calcium
Targeted treatment for high risk patients (ie: bisphosphonate)

165
Q

Describe GI side effects transplant

A

H2 antagonist or PPI for dyspepsia or to minimize side effects from intensive immunosuppression (continued forever or d/c after)
PPI prophylaxis routine in many centers

166
Q

describe GI side effects and drugs

A
167
Q

Describe CVD in transplant

A

Major cause of morbidity and mortality
Framingham underestimates risk
Decrease risk factors (control BP, diabetes, stop smoking, weight loss, manage hyperlipidemia)

168
Q

Describe Hyperlipidemia in Transplant

A

SRL&raquo_space;CSA, TAC

Statins 1st line but increased risk of myopathy/rhabdomyalysis

169
Q

Drug Int Hyperlipidemia MEds

A

increased levels of statins, start at ½ dose & titrate pending effect and tolerance

Cholestyramine/colestipol adversely affect absorption of MMF, CSA

Ezetimibe in combo with CSA can increase levels of both drugs – caution with CNIs!

170
Q

Hypertension Transplant

A

Occurs in 50-90% kidney & liver & almost all hearts

CSA, TAC

May be difficult to treat

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

171
Q

Tx HTN in Transplant

A
172
Q

Anemia in Transplant and TX

A
173
Q

Describe renal insufficiency in transplant

A

Complication of all solid organ transplant

CKD affects 30-50% of non-renal transplants

Modify medications/procedures to minimize renal adverse effects  DO not want to use NSAIDs here, radiocontrast with imaging

174
Q

What is NODAT?

A

NEW ONSET DIABETES AFTER TRANSPLANT (NODAT)

175
Q

Describe NODAT and TX

A
176
Q

Describe GOut in TX

A
177
Q

Tx of Gout in Transplant

A

Avoid NSAIDS
counsel on diet
may use steroids, colchicine or allopurinol but dose adjust based on renal function & manufacturer recommendation

178
Q

Electrolyte Disturbance in Transplant

A

Oral or IV supplementation
correct underlying cause if possible
IV supllementation – earlier post-transplant – first year
Sorts its self out over time

179
Q

What are the electrolytes of cocnern post-transplant?

A

Magnesium, Phosphate and Calcium Supllementation (CNI decraese Mg and PO4)

K+ increased by CNI and high after transplant
Kaxylate, Sodium polystyrene sulfonate

180
Q

Fertility Consideration Transplant

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

181
Q

Immunizations in Transplant

A

No live vaccines!
Vaccine response post transplanted is often blunted
Influenza yearly is recommended for all patients

182
Q

Drug Inetractions Transplant

A
183
Q

Herbal Products Transplant

A
184
Q

Non-adherence in Transplant

A
185
Q

Which adjunct medications are often started after a transplant?

A

Labetalol and clonidine or Nifedipine –> Blood Pressure control and Protect the kidney

ACEi and Arb not started right after transplant –>More often than not, will not start it until after
CCB
ACE/ARBs are first line eventually

ASA sometimes prophylactically prescribed to prevent bleeding

186
Q

Role of Community Pharamcist in Transplant

A

Identify and address drug interactions
Assess adherence
Identify and triage red flags
Liaison for communication

187
Q

Types of Living Donors

A

Paired Exchange: An incompatible donor/ recipient pair (such as a mother and son that don’t have compatible blood types) are matched with another incompatible donor/recipient pair for a “swap”

Altrusitic DOnor: a person who wishes to donate a kidney to a person with advanced kidney disease, who he or she does not know

188
Q

Risks of donating a KIdney

A

Risks of surgery
Slight increased risk of high blood pressure
Slight increased incidence of kidney failure
Possibility of injuring the remaining kidney
Slight risk of developing a disease of the remaining kidney
Some people also experience psychological difficulties, although most donors are satisfied with their decision to donate a kidney

189
Q

Allocation of Organs

A

In Canada, opt-in system for donation
Nova-Scotia - Opt-out system

Therapeutics 358 Final (3 decks)

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