Transplant Stuff Flashcards
What is an autograft?
Self to self transplant (CABG, skin graft)
What is an allograft?
Occurring between two of the same species
What is a xenograft?
One species to another
The majority of transplanted organs are obtained from ___________ (living / deceased) donors.
deceased
What drug coverage program within the province covers the medication costs of a kidney transplant patient?
SAIL
Most solid organ transplants (other than kidneys) are conducted in what Canadian city?
Edmonton (occasionally Winnipeg)
T or F: All medications for any solid organ transplant patient are covered by SAIL.
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).
The subunit on APCs that distinguishes ‘self’ from ‘non-self’ is defined as what?
MHC
What MHC Class (I or II) do T Helper cells recognize?
Class II
What MHC Class (I or II) do Cytotoxic T Cells recognize?
Class I
Which HLA Class (I, II, or III) does NOT play a role in graft rejection?
HLA Class III
Describe Signal I in the “T Cell Three Signal Model”.
“Recognition”
MHC Class II antigen on APC shown to T Helper cells; precedes Calcineurin pathway activation & IL-2 production.
Describe Signal II in the “T Cell Three Signal Model”.
“Activation”
CD80 & CD86 on APC interact with CD28 on Cytotoxic T Cells; leads to T Cell activation & graft destruction.
Describe Signal III in the “T Cell Three Signal Model”.
“Recruitment”
IL-2 release, binding to IL-2 Receptor located on T Cells, TOR activation & further immune recruitment.
Describe what occurs in cases of “humoral rejection”.
B cells are producing DSAs (Donor-Specific Antibodies) against allografts.
Would we want higher or lower PRA scores when assessing cross-matching compatibilities between a potential donor & recipient?
Lower (higher scores indicate broad sensitization, which is bad).
T or F: Pediatric transplant recipients < 1yr of age can receive organs from donors of differing blood types.
True… Patients over 1yr of age must have matching blood types!
Generally speaking, what form of transplant requires the greatest extent of immunosuppression? Least?
Lung (greatest)
Liver (least)
Hyperacute graft rejections are due to what?
Donor & recipient’s blood types don’t match
Acute Cellular Rejections are mediated by what cell types?
Alloreactive T Lymphocytes
Which of the following rejection subtypes is most commonly the reason for late graft loss?
Hyperacute Rejection
Acute Cellular Rejection
Humoral Rejection
Chronic Rejection
Chronic Rejection
When is the risk of acute graft rejection highest?
Within the first 3mths post-transplant
What constitutes “Induction Therapy”?
1) IL-2 Antagonist (Basiliximab) or Lymphocyte Depleting AB (Antithymocyte Globulin)
2) Corticosteroid (Prednisone)
3) Antiproliferative (Azathioprine or Mycophenolate)
4) CNI (Cyclosporine or Tacrolimus)
T or F: Basiliximab has many DDIs & must be closely monitored.
False… No significant DDIs noted & generally well tolerated.
What is the standardized IV dosing regimen all transplant patients receiving Basiliximab get?
20mg IV prior to transplant, repeat on Day 4 or 5
When is Antithymocyte Globulin (ATG) favored over Basiliximab?
Higher potential for graft rejection
George is a 65yr old liver transplant patient and weighs 72kg. Calculate his daily dose of ATG for Induction Therapy.
72kg * 1.5mg/kg = 108mg
72 - 108mg daily x 3-10d
Major side effects with ATG use (that show increased prevalence as the additive number of doses go up)?
Bone Marrow Suppression
Liver Problems
Infusion Rxn’s
Shock
What is the desired mg/day maintenance dose of Prednisone for transplant patients?
5-10mg / day
Side effects of Azathioprine use?
Bone Marrow Suppression
Skin Lesions
Liver Issues
Pancreatitis
Balding
Significant potential DDI with Azathioprine use (Hint: ‘crystals’)?
Allopurinol; dose adjust Azathioprine (Allopurinol = XOi, meaning AZA cannot be cleared adequately).
What is the prodrug formulation of Mycophenolate?
Mycophenolate Mofetil (MMF)
Which antiproliferative drug has less off-target cellular effects (ie. Is more specific to suppressing T & B Cells)?
Mycophenolate
Side effects of Mycophenolate drugs?
GI
Neutropenia
Dual Teratogen
Anemia
T or F: Taking Mycophenolate with food reduces the extent of drug absorption.
False… Only decreases rate (but not extent) of absorption; serves purpose of promoting greater med adherence.
T or F: The enterically coated formulation of Mycophenolate (Myfortic) shows less GI side effects than Mycophenolate Mofetil.
False; developed with this in mind, but not shown clinically.
Provide some strategies for combating Mycophenolate-induced GI side effects.
-PPI / H2RA
-Loperamide
-Divide TID / QID dosing
-Switch formulation
-Take with food
If you want to convert an IV Cyclosporine dose into an equivalent PO dose, how would you do it?
Multiply 3x
Why are 2hr post-dose Cyclosporine levels sometimes taken (instead of troughs)?
Better correlation to AUC
Trough Cyclosporine (C0) levels can be taken ___ - ___ hrs from the last dose administered.
11.5 - 12.5hrs
In what transplant types would Cyclosporine trough levels be more likely taken?
Heart & Lung
Your pharmacy manager informs you that Prograf is on backorder & instructs you to stock up on an alternative; what do you tell them?
No comprendo amigo (cannot substitute other dosage forms such as Advagraf for it).
What is the brand name of Tacrolimus that comes in a prolonged release formulation?
Envarsus
Cyclosporine levels can be taken +/- ___mins from the observed trough, whereas Tacrolimus levels should be taken +/- ___mins from the observed trough.
Cyclo: 15mins
Tacro: 30mins
Most common ADRs with CNI drugs?
Nephrotoxicity
Neurotoxicity
Liver Toxicity
HTN
Electrolyte Imbalances
GI
How do the following electrolyte levels present in those put onto CNIs?
K+
Mg2+
PO4-
Ca2+
K+ = Up
Mg2+ = Down
PO4- = Down
Ca2+ = Up
Which drug is more likely to cause hyperlipidemia & BP increases: Cyclo or Tacro?
Cyclosporine
Which drug is more likely to cause Gout: Cyclo or Tacro?
Cyclosporine
Which drug is more likely to cause hair growth, acne, & gingival hyperplasia: Cyclo or Tacro?
Cyclosporine
Which drug is more likely to show increased GI side effects & elevate sugars: Cyclo or Tacro?
Tacrolimus
Which drug is more likely to cause balding: Cyclo or Tacro?
Tacrolimus
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
Diltiazem & Verapamil (as they can increase CNI drug levels); ACEi & ARBs do not do this.
What would you expect to happen to one’s CNI drug levels if they were given Fluconazole to clear a fungal infection?
CNI levels would increase (as Fluconazole is a potent CYP inhibitor)
What would you expect to happen to one’s CNI levels if they were given Rifampin?
Decrease (Rifampin = Potent CYP inducer)
Is Sirolimus more or less potent than CNI drugs?
Less
Which of the following drugs has the longest t1/2: Sirolimus, Tacrolimus, or Cyclosporine?
Sirolimus (t1/2 = 60hrs)
Which CYP enzyme is largely responsible for CNI / mTOR drug metabolism?
CYP3A4
When is Sirolimus use favorable?
Declining Renal Function (due to CNI use)
Presence of malignancies
Add on lung transplant & declining despite triple therapy
Unique side effects to Sirolimus?
Impaired wound healing
Mouth sores
Transient rash
Anemia
Proteinuria
T or F: There is no effective treatment for Chronic Graft Rejection.
True
At a minimum, patients who get transplants should go for bloodwork how often?
Once monthly
At </= what GFR value would a patient be listed for a kidney transplant?
</= 20mL / min
What are some signs suggesting a patient is acutely rejecting their kidney transplant?
> 30% increase SCr
Reduced urine output
Edema
Wt gain
Diffuse flank pain
What virus is a major cause of kidney graft loss?
BK / Polyoma Virus
Would a patient with compensated liver disease be eligible for a liver transplant?
No… Must be decompensated & demonstrate non-reversibility.
Most common indication for a liver transplant in children?
Primary Biliary Cirrhosis (PBC)
After what length of time post-liver transplant could we consider tapering a patient’s Mycophenolate medication?
1yr post-transplant
How might a patient’s labs present abnormally in cases of acute liver transplant rejection?
Elevated bilirubin
Elevated liver enzymes
Leukocytosis
How do the drug regimens of those receiving heart transplants differ from kidney transplant patients?
Taper off Prednisone often the case with heart transplants
What three other drugs (unrelated to immunosuppression) should heart transplant patients receive?
Statin
ASA
ACEi
The five year survival rates are lowest with what type of transplant?
Lung (~65%)
What is the most common opportunistic infection post-transplant?
Cytomegalovirus (CMV)
What situation would see the greatest potential risk of CMV infection post-transplant?
D+ R-
D+ R+
D- R-
D+ R-
Describe the prophylactic dosing regimen for CMV.
Valganciclovir 900mg OD x 100-200d
Describe the prophylactic dosing regimen for PJP.
Sulfatrim 400/80mg OD x 6-12mths
OR
Sulfatrim DS 800/160mg 3x/wk x 6-12mths
Elevated viral loads of what virus post-transplant can cause increased rates of PTLD?
Epstein-Barr Virus (EBV)
Can Framingham risk scores looking at CVD potentials be trusted in those who have received heart transplants?
No (risk is underestimated).
Is it advisable to add on Ezetimibe to somebody’s drug regimen if they’re concurrently receiving a CNI drug?
NOOOOO… Drug levels of both PSK-9i drug & CNI increase!!!
A transplant patient asks you for advice on OTC pain management; what drugs would you advise against using?
NSAIDs (due to additive nephrotoxic potential)
What agents can be used to reverse elevated potassium levels shown with transplant patients?
Sodium Polystyrene
Kayexalate
What’s our stance on giving transplant patients live vaccines?
AVOID!!!
What is the estimated percentage of graft losses attributed to medication non-adherence?
35 - 40%
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?
Increased BP
Increased incidence leftover kidney fails / gets injured / develops disease
Psychological difficulties (potential)
Name of declaration act that was established in 2008 to combat organ trafficking?
Declaration of Istanbul
