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PHAR 358 - Therapeutics (Dr. K. Halpape) > Transplant Stuff > Flashcards

Transplant Stuff Flashcards

1
Q

What is an autograft?

A

Self to self transplant (CABG, skin graft)

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2
Q

What is an allograft?

A

Occurring between two of the same species

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3
Q

What is a xenograft?

A

One species to another

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4
Q

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

A

deceased

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5
Q

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

A

SAIL

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6
Q

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

A

Edmonton (occasionally Winnipeg)

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7
Q

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

A

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).

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8
Q

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

A

MHC

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9
Q

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

A

Class II

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10
Q

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

A

Class I

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11
Q

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

A

HLA Class III

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12
Q

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

A

“Recognition”

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

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13
Q

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

A

“Activation”

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

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14
Q

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

A

“Recruitment”

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

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15
Q

Describe what occurs in cases of “humoral rejection”.

A

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

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16
Q

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

A

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

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17
Q

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

A

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

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18
Q

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

A

Lung (greatest)
Liver (least)

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19
Q

Hyperacute graft rejections are due to what?

A

Donor & recipient’s blood types don’t match

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20
Q

Acute Cellular Rejections are mediated by what cell types?

A

Alloreactive T Lymphocytes

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21
Q

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

Hyperacute Rejection
Acute Cellular Rejection
Humoral Rejection
Chronic Rejection

A

Chronic Rejection

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22
Q

When is the risk of acute graft rejection highest?

A

Within the first 3mths post-transplant

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23
Q

What constitutes “Induction Therapy”?

A

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

2) Corticosteroid (Prednisone)

3) Antiproliferative (Azathioprine or Mycophenolate)

4) CNI (Cyclosporine or Tacrolimus)

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24
Q

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

A

False… No significant DDIs noted & generally well tolerated.

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25
Q

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

A

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

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26
Q

When is Antithymocyte Globulin (ATG) favored over Basiliximab?

A

Higher potential for graft rejection

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27
Q

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

A

72kg * 1.5mg/kg = 108mg

72 - 108mg daily x 3-10d

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28
Q

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

A

Bone Marrow Suppression

Liver Problems

Infusion Rxn’s

Shock

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29
Q

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

A

5-10mg / day

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30
Q

Side effects of Azathioprine use?

A

Bone Marrow Suppression

Skin Lesions

Liver Issues

Pancreatitis

Balding

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31
Q

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

A

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

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32
Q

What is the prodrug formulation of Mycophenolate?

A

Mycophenolate Mofetil (MMF)

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33
Q

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

A

Mycophenolate

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34
Q

Side effects of Mycophenolate drugs?

A

GI
Neutropenia
Dual Teratogen
Anemia

35
Q

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

A

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

36
Q

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

A

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

37
Q

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

A

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

38
Q

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

A

Multiply 3x

39
Q

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

A

Better correlation to AUC

40
Q

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

A

11.5 - 12.5hrs

41
Q

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

A

Heart & Lung

42
Q

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

A

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

43
Q

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

A

Envarsus

44
Q

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

A

Cyclo: 15mins
Tacro: 30mins

45
Q

Most common ADRs with CNI drugs?

A

Nephrotoxicity
Neurotoxicity
Liver Toxicity
HTN
Electrolyte Imbalances
GI

46
Q

How do the following electrolyte levels present in those put onto CNIs?

K+
Mg2+
PO4-
Ca2+

A

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

47
Q

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

A

Cyclosporine

48
Q

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

A

Cyclosporine

49
Q

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

A

Cyclosporine

50
Q

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

A

Tacrolimus

51
Q

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

A

Tacrolimus

52
Q

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

A

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

53
Q

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

A

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

54
Q

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

A

Decrease (Rifampin = Potent CYP inducer)

55
Q

Is Sirolimus more or less potent than CNI drugs?

A

Less

56
Q

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

A

Sirolimus (t1/2 = 60hrs)

57
Q

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

A

CYP3A4

58
Q

When is Sirolimus use favorable?

A

Declining Renal Function (due to CNI use)

Presence of malignancies

Add on lung transplant & declining despite triple therapy

59
Q

Unique side effects to Sirolimus?

A

Impaired wound healing
Mouth sores
Transient rash
Anemia
Proteinuria

60
Q

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

A

True

61
Q

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

A

Once monthly

62
Q

At </= what GFR value would a patient be listed for a kidney transplant?

A

</= 20mL / min

63
Q

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

A

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

64
Q

What virus is a major cause of kidney graft loss?

A

BK / Polyoma Virus

65
Q

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

A

No… Must be decompensated & demonstrate non-reversibility.

66
Q

Most common indication for a liver transplant in children?

A

Primary Biliary Cirrhosis (PBC)

67
Q

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

A

1yr post-transplant

68
Q

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

A

Elevated bilirubin
Elevated liver enzymes
Leukocytosis

69
Q

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

A

Taper off Prednisone often the case with heart transplants

70
Q

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

A

Statin
ASA
ACEi

71
Q

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

A

Lung (~65%)

72
Q

What is the most common opportunistic infection post-transplant?

A

Cytomegalovirus (CMV)

73
Q

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

D+ R-
D+ R+
D- R-

A

D+ R-

74
Q

Describe the prophylactic dosing regimen for CMV.

A

Valganciclovir 900mg OD x 100-200d

75
Q

Describe the prophylactic dosing regimen for PJP.

A

Sulfatrim 400/80mg OD x 6-12mths

OR

Sulfatrim DS 800/160mg 3x/wk x 6-12mths

76
Q

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

A

Epstein-Barr Virus (EBV)

77
Q

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

A

No (risk is underestimated).

78
Q

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

A

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

79
Q

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

A

NSAIDs (due to additive nephrotoxic potential)

80
Q

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

A

Sodium Polystyrene
Kayexalate

81
Q

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

A

AVOID!!!

82
Q

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

A

35 - 40%

83
Q

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?

A

Increased BP

Increased incidence leftover kidney fails / gets injured / develops disease

Psychological difficulties (potential)

84
Q

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

A

Declaration of Istanbul

PHAR 358 - Therapeutics (Dr. K. Halpape) (8 decks)

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