Organ Transplant

Question 1

Heart Transplant Consideration

Answer 1

Drugs acting via autonomic nervous system such as atropine and digoxin will have no affect on transplanted heart

Question 2

Classification of Rejection

Answer 2

Diagnosis of rejection
-routine biopsies as surveillance
-kidney: increase scr/bun, edema, htn
-liver: increase alt, ast, alk phos, etc
-heart: sob, weak, tachy, a fib, arrythmia

Question 3

Treatment of Acute Rejection

Answer 3

1. Change Maintenance Regimen
   -Increase tacrolimus, add secondary agent, or switch from cyclosporine to tacrolimus
2. Steroid Pulse Therapy
   -Methylprednisolone 500-1000 mg IV for 3-5 days then taper to pre-rejection dose
3. Steroid-resistant Therapy
   -Thymoglobulin 1-1.5 mg IV for 5 days
   -Antithymocyte (atgam) 10-15 IV for 5 days, need skin test prior to admin

Question 4

Antibody Mediated Rejection (AMR)

Answer 4

-Diagnosis: donor-specific anti-HLA antibodies as well as non-HLA antibodies
-Biopsy, complement

• No specific treatments
• Plasma exchange, IVIG, glucocorticoids
• Rituximab, bortezomib, eculizumab

Question 5

Pros and Cons of Induction Therapy

Answer 5

Indications for sensitized pts, expanded donors, steroid avoidance/calcineurin minimization

Pros
-delay use of nephrotoxic CNIs (CNI minimization)
-provide long-term immunosuppression early post-tx
-beneficial in select group of sensitized patients

Cons
-can increase risk of infectious and malignant complications
-significant adverse effects with depleting agents (thymoglobulin)

Question 6

Calcineurin Inhibitors: Cyclosporine and Tacrolimus

Answer 6

-Backbone of most immunosuppressive regimens
-Similar MOA, AE, DDI
-NOT used together
-Tacrolimus used more
-RCTs show superior efficacy to tacrolimus to prevent acute rejection

Question 7

Cyclosporine

Answer 7

-Primarily used as alternative to tacrolimus
*ex: neurotoxicity, uncontrolled diabetes

-Ex Dosing 5-15 mg/kg/day BID
-Thera Range: 100-250 ng/ml

Question 8

Tacrolimus

Answer 8

Primary agent (used with 1-2 other agents)

CAN TREAT REJECTION (in some cases)

-Greater incidence: hyperglycemia, tremor
-Lower incidence: HTN, gingival hyperplasia, hirsutism

-Ex Dosing: 0.15-0.3 mg/kg/day BID
-Thera Range: 5-15 ng/ml

Question 9

Example CNI Drug Interactions
for Tacro/Cyclo

Answer 9

-Grapefruit juice
-Azole antifungals
-“Mycins”
-Non dhp CCB
-Amiodarone
-Rifampin
-Phenytoin, phenobarbital
-Carbamazepine
-SJW
GRANMA got CPS called on her

CYCLO ONLY: Increased conc of: statin, digoxin, “limus”
sike CYC it was her LSD

Question 10

Calcineurin Inhibitor Nephrotoxicity (CNI) Tacrolimus and Cyclosporine

Answer 10

-Acute: reversible, dose dependent

-Chronic: hyperkalemia, hypoMg, hyperuricemia, fibrosis, glomeruli affected

Question 11

Mycophenolate Mofetil (Cellcept)

Answer 11

-Most commonly used secondary agent
-Prodrug
-1 gram BID (1.5 gram if african)

DDI: AA, cholestyramine, PPI(CAP)
*cause decreased absorption

AE: GI (NVD), BM suppression

BBW in pregnancy: REMS program
*contraception during tx and 6 wk after

MM that’s CAP BG babygirl ur not pregnant

Question 12

Mycophenolic Acid (Myfortic)

Answer 12

-Active form
-Alternative to mycophenolate mofetil if GI side effects are intolerable
-720 mg BID
-Cellcept 250 = Myfortic 180

Question 13

Azathioprine

Answer 13

-Alternative to mycophenolate
-Mainly for PREGNANT PTS (or want to get preg)

Polymorphism
* Low/deficient TPMT: consider alternative agent or extreme dose reduction
* Intermediate TPMT: start at 30-70% of target dose

AE: BMS, myopathy, alopecia, pancreatitis, hepatitis(PB HAM)

DDI: allopurinol (increases aza toxicity)

PAT is in AZ eating PB HAM

Question 14

MTOR Inhibitors: Sirolimus, Everolimus

Answer 14

-Can be used as alternative to mycophenolate mofetil
-Renal sparing: use with low dose tacrolimus
-Anti-cancer, anti-atherogenic, anti-fibrotic

AE:
-Impaired wound healing
-Bone marrow, dyslipidemias
-Proteinuria, angioedema
-Mouth ulcers
(SIR PAM has IBD forEVER)

BBW for liver/lung transplant use (SOFT), still used

Question 15

Immunosuppressive Protocols

Answer 15

1. Primary
   -Cyclosporine or Tacrolimus
2. Secondary
   -Mycophenolate, Sirolimus, Everolimus, or Azathioprine
3. Steroid
4. +/- Induction Agent
   -Antithymocyte globulin, Basiliximab

most common: tacro + mmf + steroid

Question 16

Bacterial Infections Post-Transplant

Answer 16

-UTIs, biliary tract infections, intrathoracic infections

-Surgical prophylaxis with abx given preop

Question 17

Cytomegalovirus (CMV)

Answer 17

Risk: 1-6 mon post transplant
*If D+/R-, D or R CMV+

Prophylaxis
-Valganciclover 900 for 3-12 months

Tx
-Ganciclover 5 mg/kg IV q12 hr
-Alt: CMV hyperimmune globulin, foscarnet

Question 18

Fungal Prophylaxis

Answer 18

Candida
-Only Liver: fluconazole

Aspergillus
-Lung: voriconazole/itraconazole, or posaconazole/isavuconazole (VOIT or POIS)
-Liver: voriconazole

Question 19

PJP - Pneumocystis jirovecii pneumonia

Answer 19

Trimethoprim/sulfamethoxazole
-400/80 daily or 800/160 3x week
-6 mo to 1 yr
-also UTI prophylaxis

Alternatives
-Dapsone 50-100 mg (sulfa allergy, check G6PD)
-Atovaquone 1500 mg (if pt has leukopenia)
-Pentamidine 300 mg nebulized

Question 20

Post-Transplant Management HTN

Answer 20

• Lifestyle modifications
• Calcium channel blockers (AM,NIF - counteract vasoconstriction of CNIs)
• ACE inhibitors (DM/CKD/proteinuria/check K)
• BB
• Diuretics

Question 21

Post-Transplant Management - Hyperlipidemia

Answer 21

Statins, HMG-CoAinhibitors
- Check drug interactions

Question 22

New Onset Diabetes After Transplant (NODAT)

Answer 22

• FPG ≥ 126 mg/dL
• RPG ≥ 200 mg/dL
• A1C ≥ 6.5%

bc of steroids, tacro > cyclo

Insulin, oral agents, diet/exercise

Question 23

Post-Transplant Malignancies

Answer 23

Increased risk for any malignancy due to immunosuppression

-Skin cancer: SUNSCREEN
-Post Transplant Lymph Disorder: Reduction of immunosuppression, IG, Interferon a, Rituximab