Organ Transplant Flashcards
Heart Transplant Consideration
Drugs acting via autonomic nervous system such as atropine and digoxin will have no affect on transplanted heart
Classification of Rejection
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
Treatment of Acute Rejection
- Change Maintenance Regimen
-Increase tacrolimus, add secondary agent, or switch from cyclosporine to tacrolimus - Steroid Pulse Therapy
-Methylprednisolone 500-1000 mg IV for 3-5 days then taper to pre-rejection dose - 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
Antibody Mediated Rejection (AMR)
-Diagnosis: donor-specific anti-HLA antibodies as well as non-HLA antibodies
-Biopsy, complement
- No specific treatments
- Plasma exchange, IVIG, glucocorticoids
- Rituximab, bortezomib, eculizumab
Pros and Cons of Induction Therapy
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)
Calcineurin Inhibitors: Cyclosporine and Tacrolimus
-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
Cyclosporine
-Primarily used as alternative to tacrolimus
*ex: neurotoxicity, uncontrolled diabetes
-Ex Dosing 5-15 mg/kg/day BID
-Thera Range: 100-250 ng/ml
Tacrolimus
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
Example CNI Drug Interactions
for Tacro/Cyclo
-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
Calcineurin Inhibitor Nephrotoxicity (CNI) Tacrolimus and Cyclosporine
-Acute: reversible, dose dependent
-Chronic: hyperkalemia, hypoMg, hyperuricemia, fibrosis, glomeruli affected
Mycophenolate Mofetil (Cellcept)
-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
Mycophenolic Acid (Myfortic)
-Active form
-Alternative to mycophenolate mofetil if GI side effects are intolerable
-720 mg BID
-Cellcept 250 = Myfortic 180
Azathioprine
-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
MTOR Inhibitors: Sirolimus, Everolimus
-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
Immunosuppressive Protocols
- Primary
-Cyclosporine or Tacrolimus - Secondary
-Mycophenolate, Sirolimus, Everolimus, or Azathioprine - Steroid
- +/- Induction Agent
-Antithymocyte globulin, Basiliximab
most common: tacro + mmf + steroid
