Solid Organ Transplantation

Front 1

What are some reasons for a kidney transplant?

Back 1

1. ESRD from DM
2. HTN
3. Glomerulonephritis

Front 2

What are some reasons for a liver transplant?

Back 2

ESLD from noncholestatic cirrhosis (Hep B or C, alcoholic cirrhosis, cryptogenic cirrhosis, autoimmune hepatitis)

Front 3

What are some reasons for a heart transplant?

Back 3

NYHA class III or IV sx from idiopathic cardiomyopathy or ischemic heart disease

Front 4

Who cannot receive a transplant?

Back 4

1. Any condition leaving pt too unstable to survive surgery
2. Malignancy within last 5 years
3. Active alcohol or substance abuse
4. Recurrence of Hep C after liver transplant
5. Active infection
6. Severe pulmonary HTN (for a heart)
7. Elderly patients or those with HIV will be transplanted in some centers but not others

Front 5

Who cannot donate?

Back 5

ABSOLUTE EXCLUSIONS:
1. HIV positive
2. Active cancer
3. Systemic infection

(no upper or lower age limit)

Front 6

When waiting for a kidney transplant, what type of treatment should pt receive?

Back 6

Dialysis

Front 7

When waiting for a heart transplant, what treatment can be used?

Back 7

Left ventricular assist device (L-VAD)

-can live about 2 years with this

Front 8

When waiting for a liver transplant, are there treatment options?

Back 8

Only investigational options - hepatocyte transplantation, artificial liver support

Front 9

True or False: Native kidneys are usually removed during a transplant.

Back 9

FALSE. Most often native kidney is not removed, so patient has 3 kidneys have transplant.

Front 10

What is the IMMEDIATE benefit of a kidney transplant?

Back 10

Normalization of GFR

Front 11

What are the LONG-TERM benefits of a kidney transplant?

Back 11

Resolution of problems caused by chronic renal failure such as Ca/Phos imbalance, anemia, lipids, etc...

Front 12

What is the treatment for delayed graft function?

Back 12

Dialysis within 7 days of transplantation (primary cause is ATN)

Front 13

Which organ is the least immunogenic?

Back 13

Liver

Front 14

What are 3 consequences of liver transplant?

Back 14

1. post-op fluid, electrolyte and nutritional abnormalities
2. Changes in serum proteins, metabolism/elimination, etc
3. Biliary tract dysfunction (altered absorption of fat and fat-soluble drugs)

Front 15

After a heart transplant, the heart is denervated which means:

Back 15

1. the patient will NOT experience angina
2. HR will NOT increase acutely in response to hypotension or exercise

Front 16

What is coronary arterial vasculopathy (CAV)?

Back 16

A result of heart transplant; an autoimmune reaction in which the lumen gets thicker.

Front 17

Why is HTN a consequence of heart transplant?

Back 17

Due to high levels of catecholamines and systemic vascular resistance

Front 18

What test is done annually following a heart transplant?

Back 18

Right-heart cath (can be risky)

Front 19

How is organ rejection diagnosed?

Back 19

Biopsy of organ

Front 20

What are the 3 types of organ rejection?

Back 20

1. Hyperacute
2. Acute
3. Chronic

Front 21

What are the characteristics of HYPERACUTE rejection and how is it treated?

Back 21

Occurs IMMEDIATELY due to ABO mismatch (wrong blood type - should never happen!)

Tmt: Supportive care and retransplantation

Front 22

What are the characteristics of ACUTE rejection (when does it occur, how and what are the symptoms) and how it is treated?

Back 22

When: Most commonly occurs in the first few months but can occur anytime
How: Cytotoxic T-lymphocytes infiltrate graft and destroy healthy cells
Symptoms: Pain over graft site, lethargy, fever
Tmt: Reversible within 1-3 days if treated (high levels of immunosuppressants)

Front 23

What occurs in CHRONIC rejection and is there treatment?

Back 23

Persistent perivascular and interstitial inflammation
(occurs over time due to the effects of being "foreign", meds and other disease states that overcome the transplanted organ)

NOT currently reversible and results in loss of allograft

Front 24

What is the approach to immunosuppression?

Back 24

1. Balance
-Prevent rejection vs. ADEs of therapy
2. Multi-drug approach
-Complex pathways causing rejection
-Allows lower doses of each drug to minimize adverse effects

Front 25

What is given at the time of transplant or during an episode of acute rejection?

Back 25

High level of immunosuppression

Front 26

What are the 2 strategies for induction therapy?

Back 26

1. All patients
2. High risk patients only: previous transplants, multiple pregnancies, non-Caucasian

Front 27

Which polyclonal antibody is an equine anti-thymocyte globulin?

Back 27

ATG (ATGAM) - recommend skin test first

Front 28

Which polyclonal antibody is a rabbit anti-thymocyte globulin and it is more or less immunogenic?

Back 28

RATG (Thymoglobulin) - LESS immunogenic

Front 29

What is the black box warning for ATG and RATG?

Back 29

1. Physicians must be EXPERIENCED in immunosuppressive therapy

2. Pts receiving these meds should be treated in adequately EQUIPPED FACILITIES

Front 30

What are the ADEs of ATG and RATG?

Back 30

1. Infusion-associated reactions
2. Cytokine release syndrome (CRS)
3. Anaphylaxis
4. Anemia, leukopenia, thrombocytopenia
5. Infections
6. Malignancy
7. Serum sickness (more with ATG)

Front 31

What symptoms are associated with infusion-related reactions and how can these be reduced?

Back 31

Sx: Fever, chills/rigors, dyspnea, n/v/d, HoTNor HTN, malaise, rash, HA

Prophylaxis: Pre-medicate with APAP, diphenhydramine, corticosteroids
-Reduce rate of infusion

Front 32

What are the symptoms of cytokine release syndrome (CRS)?

Back 32

Cardiorespiratory dysfunction - HoTN, ARDS, MI, tachycardia, pulmonary edema, and/or DEATH

Front 33

What are the characteristics and treatment of serum sickness?

Back 33

Sx: fever, rash, arthralgia, myalgia
- 5-15 days after tmt

Tmt: Manage with corticosteroids

Front 34

When should administration of additional medication be withheld?

Back 34

Systemic reaction of generalized rash, dyspnea, tachycardia, HoTN, or anaphylaxis

(Recommend skin test before ATG)

Front 35

What are the IL-2 Receptor Antagonists?

Back 35

1. Basiliximab (Simulect) - chimeric monoclonal antibody
-higher affinity
2. Daclizumab (Zenapax) - humanized monoclonal antibody
-less immunogenic

Front 36

True or False: ADEs of basiliximab and daclizumab significantly differ from placebo.

Back 36

FALSE: similar to placebo - includes malignancy and infection, hypersensitivity and CRS

Front 37

What is the name of a murine monoclonal antibody?

Back 37

Muromonab-CD 3 (OKT3)

Front 38

What is the black box warning associated with OKT3 and what precautionary measures should be taken?

Back 38

Anaphylaxis
-monitor fluid status prior to and during admin
-pre-tx with methylprednisolone to minimize cytokine release syndrome

Front 39

What are contradictions to OKT3?

Back 39

1. Hypersensitivity to this or any other product of murine origin
2. Anti-mouse antibody titers >/= 1:1,000
3. Decompensated HF or fluid overload
4. Uncontrolled HTN
5. Hx of or predisposition to seizures
6. Pregnant or breastfeeding

Front 40

What are the ADEs of OKT3?

Back 40

1. Anaphylaxis, esp on re-treatment
-can only get once
2. Cytokine release syndrome
-methylprednisolone for prevention
3. CNS
-seizures, encephalopathy, cerebral edema, aseptic, meningitis, HA
4. Infection and malignancy

Front 41

What is the black box warning/ADEs of alemtuzumab (Campath)?

Back 41

1. Pancytopenia/marrow hypoplasia, etc
2. Serious infusion rxns
3. Serious bacterial, viral, fungal, and protozoan infections

Front 42

What are the goals of maintenance therapy?

Back 42

To prevent acute and chronic rejection and minimize drug toxicity

(Most drugs used for maintenance like calcineurin inhibitors and corticosteroids can be used at high doses for acute rejection)

Front 43

What are the calcineurin inhibitors?

Back 43

1. Cyclosporine (Sandimmune, Gengraf, Neoral)
2. Tacrolimus/FK506 (Prograf)

Front 44

True or False: Sandimmune is interchangeable with Gengraf or Neoral.

Back 44

FALSE. Sandimmune is the standard cyclosporine formulation and Gengraf and Neoral are modified/microemulsion formations - these are NOT interchangeable.

Front 45

Which cyclosporine formulation (standard or modified) has a decreased AUC and Cmax and a longer half-life?

Back 45

Standard (Sandimmune)

Front 46

True or False: Hypersensitivity to Cremophor EL (polyoxyethylated castor oil) is a contraindication to cyclosporine injection.

Back 46

TRUE.

Front 47

True or False: Pts who have had rxns to IV cyclosporine CANNOT receive cyclosporine capsules or oral solution.

Back 47

FALSE. Pts with rxn to IV cyclosporine have received capsules or oral solution without incident.

Front 48

What is the contraindication to tacrolimus injection?

Back 48

Hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil)

Front 49

What are the black box warnings associated with calcineurin inhibitors?

Back 49

1. Only experienced physicians/adequate facilities
2. Standard - admin w/ corticosteroids
3. Modified - may be admin w/ other suppressive agents in kidney, liver, and heart transplants
4. Modified - inc bioavailability compared to standard; troughs will be higher
5. Monitoring drug levels recommended

Front 50

What are the adverse effects common to both calcineurin inhibitors (cyclosporine and tacrolimus)?

Back 50

1. Hepatotoxicity
2. Increased K+
3. Hyperglycemia
4. Hyperlipidemia
5. HTN
6. Infections- new & reactivation
7. Malignancy
8. Nephrotoxicity
9. Neurotoxicity - tremor, HA, PN

Front 51

What are the adverse effects unique to cyclosporine?

Back 51

1. Acne
2. Gingival hyperplasia
3. Hirsutism

"HAG"

Front 52

What are the adverse effects unique to tacrolimus?

Back 52

1. Alopecia
2. Diarrhea, nausea
3. DECREASED Mg***
4. Pruritis

Front 53

True or False: Acute nephrotoxicity caused by calcineurin inhibitors is dose dependent and reversible.

Back 53

TRUE

Front 54

True or False: Chronic nephrotoxicity caused by calcineurin inhibitors is reversible.

Back 54

FALSE

Front 55

What is needed to differentiate between renal toxicity and kidney rejection in patients taking calcineurin inhibitors?

Back 55

Biopsy - 20% of patients will have both

Front 56

What are the causes of acute nephrotoxicity in patients taking calcineurin inhibitors?

Back 56

1. renal vasoconstriction
2. decreased renal blood flow
3. decreased GFR
4. increased Na+ re-absorption in proximal tubules

Front 57

What are the causes of chronic nephrotoxicity in patients taking calcineurin inhibitors?

Back 57

HTN and DMI

Front 58

Calcineurin inhibitors are substrates of: ___ & _-__ and inhibitors of ___.

Back 58

-substrates of 3A4 & P-gp
-inhibitors of 3A4
(caution HMG-CoA reductase inhibitors)

Front 59

Some things that may INCREASE the concentration of calcineurin inhibitors:

Back 59

Antifungals, antibiotics, methylprednisolone, grape fruit juice

Front 60

Something that may DECREASE concentration of calcineurin inhibitors:

Back 60

St. John's Wort

Front 61

True or False: Calcineurin inhibitors can be taken without regard to meals.

Back 61

FALSE. Calcineurin inhibitors must be taken consistently with regard to meal.

Front 62

How should tacrolimus be taken with regard to antacids/positive cations?

Back 62

Separate by 2 hours

Front 63

What should be avoided with calcineurin inhibitors?

Back 63

1. Live vaccines
2. Other drugs causing increased K+
3. Other nephrotoxic drugs

Front 64

What are some drugs that may potentiate renal dysfunction?

Back 64

Antibiotics, antifungals, naproxen

Front 65

What are the mammalian target of rapamycin (mTOR) inhibitors?

Back 65

1. Sirolimus (Rapamune)
2. Everolimus (Zortress)

Front 66

True or False: Different assays used for monitoring Sirolimus are interchangeable.

Back 66

FALSE. Chromatographic and immunoassay methods may yield different concentration levels.

Front 67

What is the BBW for mTOR inhibitors?

Back 67

1. Only experienced physicians/adequate facilities
2. Increased risk of infection and malignancies
3. NOT recommended in liver or lung
4. Decreased dose of cyclosporine with everolimus to decrease renal dysfunction
5. Increased risk of kidney arterial and venous thrombosis resulting in graft loss with everolimus

Front 68

What are the adverse reactions mTOR inhibitors?

Back 68

1. Anemia/thrombocytopenia
2. Angioedema
3. Arthralgia
4. Delayed wound healing/dehiscence
5. Fluid accumulation
6. Hypercholesterolemia/triglyceridemia
7. HTN
8. Infections
9. Interstitial lung disease
10.Malignancy
11. Nephrotoxicity

Front 69

What adverse effects are unique to everolimus?

Back 69

1. Kidney thrombosis
2. Male infertility

Front 70

mTOR inhibitors are metabolized by: ___ & ___

Back 70

3A4 & P-gp (consistent with CIs)

Front 71

How should mTOR inhibitors be taken with regard to cyclosporine (inhibits 3A4 & P-gp)?

Back 71

Sirolimus: take 4 hours AFTER cyclosporine

Everolimus: Take SAME TIME as cyclosporine

Caution w/ dose adjustments

Front 72

True or False: mTOR inhibitors can be taken without regard to meals.

Back 72

FALSE - should be taken consistently with regard to meals

Front 73

True or False: grapefruit juice can increase levels of mTOR.

Back 73

TRUE

Front 74

True or False: Live vaccines can be given in patients taking mTOR inhibitors.

Back 74

FALSE - avoid intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, TY21a typhoid vaccines, etc

Front 75

Mycophenolic Acid (MPA) is part of what class of drugs?

Back 75

Antimetabolites

Front 76

What are the 2 mycophenolic acid drugs?

Back 76

1. Mycophenolate mofetil (MMF) (Cellcept)
2. Mycophenolate sodium - delayed release (Myfortic)

Front 77

What are the black box warnings for mycophenolic acid?

Back 77

1.Only experienced physicians/adequate facilities
2. Females of childbearing potential must use contraception: use during pregnancy associated with increased risk of pregnancy loss and congenital malformations (use 2 forms of BC)

Front 78

What are the adverse effects associated with MPAs?

Back 78

1. GI - abdominal pain, n/v/d
-split dosing if needed
2. Infection
3. Malignancy/lymphoma
4. Neutropenia; also anemia & thrombocytopenia
5. Pure Red Cell Aplasia

Front 79

What testing should be done to monitor for neutropenia associated with MPA?

Back 79

CBC weekly during 1st month, twice monthly in the 2nd & 3rd months, then monthly through 1st year

Front 80

True or False: MPA should be taken with food.

Back 80

FALSE - but take regular release with food if severe GI upset

Front 81

Why should cholestyramine be avoided with MPA?

Back 81

Decreased AUC because of decreased enterohepatic recirculation

Front 82

How should MPA be taken with regard to antacids/phosphate binders/Al/Mg/Fe?

Back 82

Antacids/phosphate binders/Al/Mg/Fe should be administered 2 hours AFTER MPA

Front 83

What is the interaction between MPA and oral contraceptives?

Back 83

Decreased blood levels of hormones

Front 84

What can happen if MPA and acyclovir/ganciclovir are administered together?

Back 84

Concentrations of both can be increased; should be cautioned in renal impairment (can cause acute renal failure)

Front 85

True or False: Live attenuated vaccines can be given to patients taking MPA.

Back 85

FALSE

Front 86

True or False: MPA delayed-release is pH dependent.

Back 86

TRUE - tab does not release MPA when pH < 5, but is soluble in neutral pH

Front 87

Azathioprine (6-MP) is part of what drug class?

Back 87

Antimetabolites

Front 88

What are the black box warnings for 6-MP?

Back 88

1. Increased risk of neoplasia
2. Mutagenic potential
3. Hematologic toxicities

Front 89

What are the adverse effects of 6-MP?

Back 89

1.GI - severe n/v
-divide dose, give with food
2. Hepatotoxicity
3. Infection
4. Leukopenia, macrocytic anemia, pancytopenia, thrombocytopenia
5. Malignancy
6. Pregnancy category D

Front 90

What are the drug interactions associated with 6-MP?

Back 90

1. xanthine oxidase inhibitors - allopurinol
-decrease azathioprine 1/4 to 1/3 of normal dose
2. avoid live vaccines

Front 91

What are the corticosteroids?

Back 91

Methylprednisolone and prednisone

Front 92

What are the adverse effects of corticosteroids?

Back 92

1. Adrenal suppression/insufficiency
2. Cataracts/glaucoma
3. Fat redistribution
4. Hyperglycemia
5. HTN
6. Immunosuppression
7. Impaired wound healing
8. Infection
9. Muscular atrophy
10. Na+/H2O rentention
11. Osteoporosis
12. Peptic ulcers
13. Psych effects
14. Stunted growth
15. Thinning of the skin
16. Weight gain

Front 93

What are the complications of preventing rejection?

Back 93

1. HTN
2. Hyperlipidemia
3. DM
4. Infection
5. CMV
6. Malignancy

Front 94

What are some reasons that preventing rejection causes HTN?

Back 94

-CIs, mTORs, steroids, & impaired kidney graft function

Front 95

What can be given to transplant patients who experience HTN?

Back 95

All meds are effective, but some avoid ACE/ARB in renal transplant due to the potential for nephrotoxicity

Front 96

What can cause hyperlipidemia in transplant patients?

Back 96

CIs and mTORs

Front 97

What are some treatment options for patients who experience hyperlipidemia after transplant?

Back 97

-Statins and diet are treatment of choice
(Pravastatin often preferred because it is not metabolized by 3A4)
-Separate bild acid-binding resins by at least 2 hours
(completely avoid with MPA)

Front 98

What can cause DM in transplant patients?

Back 98

CIs and steroids

Front 99

What should be used to treat DM in transplant patients?

Back 99

-Meds that aren't affected by changes in renal function (prefer glyburide)

Front 100

What are the sources of infection associated with transplant?

Back 100

-Donor-derived
-Recipient-derived
-Nosocomial

Front 101

What should be given to prevent infection in transplant patients?

Back 101

Vaccines (get before transmission)

Front 102

What types of infection are associated with transplants?

Back 102

1. Bacterial infections
-urinary tract, wounds, vascular assess sites
2. Cytomegalovirus (CMV)
-ganciclovir/valganciclovir
3. Herpes simplex virus (HSV)
-acyclovir/valacyclovir
4.Pneumocystis carinii/jiroveci
-bactrim
5. BK virus
-reduce immunosuppression
6. Hepatitis B&C

Front 103

What causes CMV in transplant patients?

Back 103

Comes from herpes virus group
(associated with increased mortality and acute and chronic rejection)

Front 104

What is the universal vs. preemptive therapy for CMV?

Back 104

-immediately after transplant for 100+ days
-monitoring for CMV viremia

Front 105

What are some characteristics of malignancy in transplant patients?

Back 105

1. decreased acute rejection and increased patient survival -> increased lifetime exposure to immunosuppression
2. most common cause of death in the 6-10 years post-transplant
3. skin cancers are most common
4. high prevalence of lymphomas
5. post-transplantation lymphoproliferative disorders (PTLD)