Transplant Stuff

Question 1

What is an autograft?

Answer 1

Self to self transplant (CABG, skin graft)

Question 2

What is an allograft?

Answer 2

Occurring between two of the same species

Question 3

What is a xenograft?

Answer 3

One species to another

Question 4

The majority of transplanted organs are obtained from ___________ (living / deceased) donors.

Answer 4

deceased

Question 5

What drug coverage program within the province covers the medication costs of a kidney transplant patient?

Answer 5

SAIL

Question 6

Most solid organ transplants (other than kidneys) are conducted in what Canadian city?

Answer 6

Edmonton (occasionally Winnipeg)

Question 7

T or F: All medications for any solid organ transplant patient are covered by SAIL.

Answer 7

FALSE… EDS covers the costs of immunomodulator drugs in full, but SAIL will not pick up the costs of any supportive medications a patient may require (e.g. PPI / H2RA for GI upset related to immunomodulator use).

Question 8

The subunit on APCs that distinguishes ‘self’ from ‘non-self’ is defined as what?

Answer 8

MHC

Question 9

What MHC Class (I or II) do T Helper cells recognize?

Answer 9

Class II

Question 10

What MHC Class (I or II) do Cytotoxic T Cells recognize?

Answer 10

Class I

Question 11

Which HLA Class (I, II, or III) does NOT play a role in graft rejection?

Answer 11

HLA Class III

Question 12

Describe Signal I in the “T Cell Three Signal Model”.

Answer 12

“Recognition”

MHC Class II antigen on APC shown to T Helper cells; precedes Calcineurin pathway activation & IL-2 production.

Question 13

Describe Signal II in the “T Cell Three Signal Model”.

Answer 13

“Activation”

CD80 & CD86 on APC interact with CD28 on Cytotoxic T Cells; leads to T Cell activation & graft destruction.

Question 14

Describe Signal III in the “T Cell Three Signal Model”.

Answer 14

“Recruitment”

IL-2 release, binding to IL-2 Receptor located on T Cells, TOR activation & further immune recruitment.

Question 15

Describe what occurs in cases of “humoral rejection”.

Answer 15

B cells are producing DSAs (Donor-Specific Antibodies) against allografts.

Question 16

Would we want higher or lower PRA scores when assessing cross-matching compatibilities between a potential donor & recipient?

Answer 16

Lower (higher scores indicate broad sensitization, which is bad).

Question 17

T or F: Pediatric transplant recipients < 1yr of age can receive organs from donors of differing blood types.

Answer 17

True… Patients over 1yr of age must have matching blood types!

Question 18

Generally speaking, what form of transplant requires the greatest extent of immunosuppression? Least?

Answer 18

Lung (greatest)
Liver (least)

Question 19

Hyperacute graft rejections are due to what?

Answer 19

Donor & recipient’s blood types don’t match

Question 20

Acute Cellular Rejections are mediated by what cell types?

Answer 20

Alloreactive T Lymphocytes

Question 21

Which of the following rejection subtypes is most commonly the reason for late graft loss?

Hyperacute Rejection
Acute Cellular Rejection
Humoral Rejection
Chronic Rejection

Answer 21

Chronic Rejection

Question 22

When is the risk of acute graft rejection highest?

Answer 22

Within the first 3mths post-transplant

Question 23

What constitutes “Induction Therapy”?

Answer 23

1) IL-2 Antagonist (Basiliximab) or Lymphocyte Depleting AB (Antithymocyte Globulin)

2) Corticosteroid (Prednisone)

3) Antiproliferative (Azathioprine or Mycophenolate)

4) CNI (Cyclosporine or Tacrolimus)

Question 24

T or F: Basiliximab has many DDIs & must be closely monitored.

Answer 24

False… No significant DDIs noted & generally well tolerated.

Question 25

What is the standardized IV dosing regimen all transplant patients receiving Basiliximab get?

Answer 25

20mg IV prior to transplant, repeat on Day 4 or 5

Question 26

When is Antithymocyte Globulin (ATG) favored over Basiliximab?

Answer 26

Higher potential for graft rejection

Question 27

George is a 65yr old liver transplant patient and weighs 72kg. Calculate his daily dose of ATG for Induction Therapy.

Answer 27

72kg * 1.5mg/kg = 108mg 72 - 108mg daily x 3-10d

Question 28

Major side effects with ATG use (that show increased prevalence as the additive number of doses go up)?

Answer 28

Bone Marrow Suppression Liver Problems Infusion Rxn's Shock

Question 29

What is the desired mg/day maintenance dose of Prednisone for transplant patients?

Answer 29

5-10mg / day

Question 30

Side effects of Azathioprine use?

Answer 30

Bone Marrow Suppression Skin Lesions Liver Issues Pancreatitis Balding

Question 31

Significant potential DDI with Azathioprine use (Hint: 'crystals')?

Answer 31

Allopurinol; dose adjust Azathioprine (Allopurinol = XOi, meaning AZA cannot be cleared adequately).

Question 32

What is the prodrug formulation of Mycophenolate?

Answer 32

Mycophenolate Mofetil (MMF)

Question 33

Which antiproliferative drug has less off-target cellular effects (ie. Is more specific to suppressing T & B Cells)?

Answer 33

Mycophenolate

Question 34

Side effects of Mycophenolate drugs?

Answer 34

GI Neutropenia Dual Teratogen Anemia

Question 35

T or F: Taking Mycophenolate with food reduces the extent of drug absorption.

Answer 35

False... Only decreases rate (but not extent) of absorption; serves purpose of promoting greater med adherence.

Question 36

T or F: The enterically coated formulation of Mycophenolate (Myfortic) shows less GI side effects than Mycophenolate Mofetil.

Answer 36

False; developed with this in mind, but not shown clinically.

Question 37

Provide some strategies for combating Mycophenolate-induced GI side effects.

Answer 37

-PPI / H2RA -Loperamide -Divide TID / QID dosing -Switch formulation -Take with food

Question 38

If you want to convert an IV Cyclosporine dose into an equivalent PO dose, how would you do it?

Answer 38

Multiply 3x

Question 39

Why are 2hr post-dose Cyclosporine levels sometimes taken (instead of troughs)?

Answer 39

Better correlation to AUC

Question 40

Trough Cyclosporine (C0) levels can be taken ___ - ___ hrs from the last dose administered.

Answer 40

11.5 - 12.5hrs

Question 41

In what transplant types would Cyclosporine trough levels be more likely taken?

Answer 41

Heart & Lung

Question 42

Your pharmacy manager informs you that Prograf is on backorder & instructs you to stock up on an alternative; what do you tell them?

Answer 42

No comprendo amigo (cannot substitute other dosage forms such as Advagraf for it).

Question 43

What is the brand name of Tacrolimus that comes in a prolonged release formulation?

Answer 43

Envarsus

Question 44

Cyclosporine levels can be taken +/- ___mins from the observed trough, whereas Tacrolimus levels should be taken +/- ___mins from the observed trough.

Answer 44

Cyclo: 15mins Tacro: 30mins

Question 45

Most common ADRs with CNI drugs?

Answer 45

Nephrotoxicity Neurotoxicity Liver Toxicity HTN Electrolyte Imbalances GI

Question 46

How do the following electrolyte levels present in those put onto CNIs? K+ Mg2+ PO4- Ca2+

Answer 46

K+ = Up Mg2+ = Down PO4- = Down Ca2+ = Up

Question 47

Which drug is more likely to cause hyperlipidemia & BP increases: Cyclo or Tacro?

Answer 47

Cyclosporine

Question 48

Which drug is more likely to cause Gout: Cyclo or Tacro?

Answer 48

Cyclosporine

Question 49

Which drug is more likely to cause hair growth, acne, & gingival hyperplasia: Cyclo or Tacro?

Answer 49

Cyclosporine

Question 50

Which drug is more likely to show increased GI side effects & elevate sugars: Cyclo or Tacro?

Answer 50

Tacrolimus

Question 51

Which drug is more likely to cause balding: Cyclo or Tacro?

Answer 51

Tacrolimus

Question 52

I'm wanting to treat a liver transplant patient's hypertension [caused by a CNI drug]; provided they have no underlying kidney issues, which drug(s) should I avoid using? Candesartan Ramipril Diltiazem Verapamil

Answer 52

Diltiazem & Verapamil (as they can increase CNI drug levels); ACEi & ARBs do not do this.

Question 53

What would you expect to happen to one's CNI drug levels if they were given Fluconazole to clear a fungal infection?

Answer 53

CNI levels would increase (as Fluconazole is a potent CYP inhibitor)

Question 54

What would you expect to happen to one's CNI levels if they were given Rifampin?

Answer 54

Decrease (Rifampin = Potent CYP inducer)

Question 55

Is Sirolimus more or less potent than CNI drugs?

Answer 55

Less

Question 56

Which of the following drugs has the longest t1/2: Sirolimus, Tacrolimus, or Cyclosporine?

Answer 56

Sirolimus (t1/2 = 60hrs)

Question 57

Which CYP enzyme is largely responsible for CNI / mTOR drug metabolism?

Answer 57

CYP3A4

Question 58

When is Sirolimus use favorable?

Answer 58

Declining Renal Function (due to CNI use) Presence of malignancies Add on lung transplant & declining despite triple therapy

Question 59

Unique side effects to Sirolimus?

Answer 59

Impaired wound healing Mouth sores Transient rash Anemia Proteinuria

Question 60

T or F: There is no effective treatment for Chronic Graft Rejection.

Answer 60

True

Question 61

At a minimum, patients who get transplants should go for bloodwork how often?

Answer 61

Once monthly

Question 62

At

Question 63

What are some signs suggesting a patient is acutely rejecting their kidney transplant?

Answer 63

>30% increase SCr Reduced urine output Edema Wt gain Diffuse flank pain

Question 64

What virus is a major cause of kidney graft loss?

Answer 64

BK / Polyoma Virus

Question 65

Would a patient with compensated liver disease be eligible for a liver transplant?

Answer 65

No... Must be decompensated & demonstrate non-reversibility.

Question 66

Most common indication for a liver transplant in children?

Answer 66

Primary Biliary Cirrhosis (PBC)

Question 67

After what length of time post-liver transplant could we consider tapering a patient's Mycophenolate medication?

Answer 67

1yr post-transplant

Question 68

How might a patient's labs present abnormally in cases of acute liver transplant rejection?

Answer 68

Elevated bilirubin Elevated liver enzymes Leukocytosis

Question 69

How do the drug regimens of those receiving heart transplants differ from kidney transplant patients?

Answer 69

Taper off Prednisone often the case with heart transplants

Question 70

What three other drugs (unrelated to immunosuppression) should heart transplant patients receive?

Answer 70

Statin ASA ACEi

Question 71

The five year survival rates are lowest with what type of transplant?

Answer 71

Lung (~65%)

Question 72

What is the most common opportunistic infection post-transplant?

Answer 72

Cytomegalovirus (CMV)

Question 73

What situation would see the greatest potential risk of CMV infection post-transplant? D+ R- D+ R+ D- R-

Answer 73

D+ R-

Question 74

Describe the prophylactic dosing regimen for CMV.

Answer 74

Valganciclovir 900mg OD x 100-200d

Question 75

Describe the prophylactic dosing regimen for PJP.

Answer 75

Sulfatrim 400/80mg OD x 6-12mths OR Sulfatrim DS 800/160mg 3x/wk x 6-12mths

Question 76

Elevated viral loads of what virus post-transplant can cause increased rates of PTLD?

Answer 76

Epstein-Barr Virus (EBV)

Question 77

Can Framingham risk scores looking at CVD potentials be trusted in those who have received heart transplants?

Answer 77

No (risk is underestimated).

Question 78

Is it advisable to add on Ezetimibe to somebody's drug regimen if they're concurrently receiving a CNI drug?

Answer 78

NOOOOO... Drug levels of both PSK-9i drug & CNI increase!!!

Question 79

A transplant patient asks you for advice on OTC pain management; what drugs would you advise against using?

Answer 79

NSAIDs (due to additive nephrotoxic potential)

Question 80

What agents can be used to reverse elevated potassium levels shown with transplant patients?

Answer 80

Sodium Polystyrene Kayexalate

Question 81

What's our stance on giving transplant patients live vaccines?

Answer 81

AVOID!!!

Question 82

What is the estimated percentage of graft losses attributed to medication non-adherence?

Answer 82

35 - 40%

Question 83

A patient tells you they're interested in donating their sibling a kidney. What are some of the risks you should advise them of with such a procedure?

Answer 83

Increased BP Increased incidence leftover kidney fails / gets injured / develops disease Psychological difficulties (potential)

Question 84

Name of declaration act that was established in 2008 to combat organ trafficking?

Answer 84

Declaration of Istanbul