Transplant Flashcards
List the type of blood groups
- Type A
- Type B
- Type AB
- Type O
What is the blood type of a person to be considered “universal donor”? Why?
- Type O
- Type O blood does not cause an immune response when received by people with type A, B or AB blood
T/F: People with type O blood will react against type A, B or AB blood so they can only receive type O
- True
What is the blood type of a person to be considered “universal receiver”? Why?
- Type AB
- Type AB blood does not react against type A, B or AB blood
People with type A blood will react against __ or __ blood
Fill in the blanks
- Type B
- Type AB
People with type B blood will react against __ or __ blood
Fill in the blanks
- Type A
- Type AB
Why tissue typing or crossmatching is performed prior to any transplant?
- To assess donor-recipient compatibility for human leukocyte antigen (HLA) and ABO blood group
Define allograft, isograft and autograft
Allograft (AKA homograft)
* Transplant of an organ or tissue from one individual to another
Isograft
* Transplanted organ from a genetically identical donor, such as an identical twin
Autograft
* Transplant in the same patient, from one site to another (e.g., autologous stem cell transplant or skin grafting)
When and why induction immunosuppression is given?
- It is given before or at the time of transplant to prevent acute rejection during the early post-transplant period
Name the commonly used induction drug
- Basiliximab an interleukin-2 (IL-2) receptor antagonist
- Only used for prevention. It is not used to treat rejection
IL-2 receptor on activated T-lymphocytes is critical for organ rejection
What is alternative to basiliximab? Why is it used?
- Antithymocyte globulin
- Used for patients with higher risk of rejection as they deplete both mature and immature T-lymphocytes, therefore can be used for both induction and treatment
These drugs are made by injecting human T-lymphocytes into animals and administering the purified antibodies that animals made back into humans
Antithymocyte globulin - MOA, brand/generic and SEs
MOA:
* Binds to antigens on T-lymphocytes (killer cells) and interferes with their function
Brand/Generic:
* Atgam - Equine
* Thymoglobulin - Rabbit
SEs:
* Infusion-related reactions - fever, chills, pruritus, rash, low BP (particularly common with first dose)
How to lessen infusion-related reactions when antithymocyte globulins are used?
- Premedicate with diphenhydramine, acetaminophen and steroids
Basiliximab - MOA
Interleukin-2 (IL-2) receptor antagonist:
- Chimeric (murine/human) monoclonal antibody that inhibits the IL-2 receptor on the surface of activated T-lymphocytes, preventing cell-mediated allograft rejection
Basiliximab (Simulect)
What is the combination of maintenance immunosuppression? Why used?
- Calcineurin inhibitor (CNI) - Tacrolimus is first line
- Antiproliferative agent - Mycophenolate is first line
- With or without steroids (typically prednisone) - if low immunological risk, it can be discontinued
– Supressing the immune system by multiple mechanisms through different drug classes is designed to lower toxicity and reduce the risk of graft rejection
Systemic steroids - MOA, short/long-term side effects
MOA:
* Naturally occuring hormones that prevent or suppress inflammation and humoral immune response
Short-term side effects:
* Fluid retention, upset stomach, emotional instability, insomnia, increased appetite, weight gain, acute rise in BG and BP
Long-term side effects:
* Adrenal supression/Cushing’s syndrome, impaired wound healing, increased BP, diabetes, acne, osteoporosis, impaired growth in children
Typically prednisone is used in this case
Antiproliferative agents - MOA, brand/generic, BWs, SEs
MOA:
* Inhibit T-lymphocyte proliferation by altering purine synthesis
Brand/Generic:
* Mycophenolate Mofetil (CellCept) - IV only stable in D5W
- Mycophenolic Acid (Myfortic) - enteric coated to ↓ diarrhea
- Not interchangeable due to absorption differences
- Both ↓ efficacy of oral contraceptives
Boxed Warnigs:
* Increased risk of infection
* Increased development of lymphoma and skin malignancies
* Increased risk of congenital malformations and spontaneous abortions when used in pregnancy
Side Effects:
* Diarrhea, GI upset
Azathioprine - Warnings
- Patients with genetic deficiency of thiopurine methyltransferase (TPMT) are at increased risk for myelosuppression
Also an antiproliferative agent
Brand names: Azasan, Imuran
Calcineurin Inhibitor - MOA, BWs, SEs, monitoring parameters for tacrolimus
Tacrolimus (Prograf):
* Do not interchange XL to IR
- IV administered as a continuous infusion; must use non-PVC bag
- Take every 12 hours on an empty stomach
- Avoid alcohol as this is CYP450 3A4 an P-gp substrate
MOA:
* Suppress cellular immunity by inhibiting T-lymphocyte activation
Boxed Warnings:
* ↑ susceptibility to infection; possible development of lymphoma
Side Effects:
* ↑BP, ↑BG, nephrotoxicity, neurotoxicity, hyperkalemia, hyperlipidemia, QT prolongation
Monitoring:
* Specific through level
* Serum electrolytes (K, Phos and Mg), renal fx, LFTs, BP, BG, lipid profile
Calcineurin Inhibitor - BWs, SEs, monitoring parameters for cyclosporine and restasis
- Restasis drops for dry eye
-
Cyclosporine
* Modified: Gengraf, Neoral
* Non-modified: Sandimmune
* Gengraf/Neoral has greater bioavailability compared to Sandimmune and cannot be used interchangeably
Boxed Warnings:
* Renal impairment
- ↑ risk of lymphoma and other malignancies, including skin cancer,
- ↑ risk of infection
- ↑BP
Side Effects:
* ↑BP,↑BG, nephropathy, hyperkalemia, hypomagnesemia, hirsutism, gingival hyperplasia, edema, neurotoxocity, QT prolongation
Monitoring:
* Through levels
- Serum electrolytes (K and Mg), renal fx, BP, BG, lipid profile
- Do not administer oral liquid from a plastic or styrofoam cup
- Numerous DIs; this is a CYP3A4 inhibitor NS CYP3A4 and P-gp substrate
Everolimus - MOA, warnings, SEs, Monitoring
MOA:
* Mammalian target of rapamycin (mTOR) kinase inhibitor - Inhibit T-lymphocyte activation and proliferation; may be synergistic with CNIs
Warnings:
* Hyperlipidemia
Side Effects:
* Peripheral edema,
* ↑BP
* Risk of renal and hepatic artery thrombosis (do not use within 30 days of transplant)
Monitoring:
Through levels, Numerous DIs: this is CYP3A4 substrate
Brand name: Zortress
Sirolimus - MOA, warnings, SEs, monitoring
MOA: Same with mTOR kinase inhibitors
Warnings:
* Impaired wound healing, hyperlipidemia
Side Effects:
* Irreversible pneumonitis/bronchitis/cough (discontinue therapy if this develops), ↑BG, peripheral edema
Monitoring:
* Through levels
- Tablets and oral solution are nor bioequivalent
- Numerous DIs: this is CYP3A4 substrate
Brand name: Rapamune
Belatacept - MOA, BWs, warnings
MOA:
* Binds to CD80 and CD86 to block T-cell costimulation and production of inflammatory mediators
Warnings:
* Treat latent TB prior to use
Brand name: Nulojix
What decreases CNI concentration?
Tacrolimus, Cyclosporin
- Tacrolimus and cyclosporin are CYP3A4 and P-gp substrates
- Cyclosporin inhibits CYP3A4
- Inducers of either enzyme (e.g., carbamazepine, nafcillin, rifampin) decrease CNI concentration
What increases CNI concentration?
Tacrolimus, Cyclosporin
- Inhibitors of CYP3A4 and P-gb increase the CNI concentration (e.g., azole antifungals, diltiazem, erythromycin)
What should be avoided when using azathioprine?
- Xanthine oxidase inhibitors (allopurinol or febuxostat)
T/F: Avoid grapefruit juice or St. John’s wort with either CNI
- True
Caution with additive drugs that raise __ with tacrolimus, steroids, cyclosporineand the mTOR inhibitors
Fill in the blank
- Blood glucose
Caution with additive drugs that are __ with tacrolimus and cyclosporin
Fill in the blank
- Nephrotoxic
Caution with additive drugs that worsen __ with the mTOR inhibitors, steroids and cyclosporine
Fill in the blank
- Lipids
Caution with additive drugs that raise __ with steroids, cyclosporine and tacrolimus
- Blood pressure
T/F: Mycophenolate can decrease levels of hormonal contraceptives
- True
What are highest incidence of adverse effects of cyclosporin and tacrolimus?
- Nephrotoxicity
- Worsening or new-onset of diabetes
- HTN
What are highest incidence of adverse effects of steroids?
- Worsening or new-onset of diabetes
- HTN
What are highest incidence of adverse effects of mTOR inhibitors?
- Worsening lipid panels
What are symptoms of infection?
- Fever of 100.4 F (38 C) or higher (lower if elderly, chills
- Cough, more sputum or change in color of sputum, sore throat
- Pain with passing urine, ear or sinus pain
- Mouth sores or wound that does not heal
All transplant recipients must self-monitor for these symptoms
How is acute rejection of the transplanted organ arises?
- Arises from either T-cell (cellular) or B-cell (humoral or antibody) mediated mechanisms
- Distinguishing the type of rejection is determined via biopsy
What is the initial approach to treat acute cellular rejection (ACR)?
- The administration of high-dose steroids and increased levels of maintenance immunosuppression
How are opportunistic infections caused?
- Caused by organisms that are everywhere in the environment rarely cause disease in patients with a functional immune system (immunocompetent)
- Prophylaxis is essential
__ cancer is common after a transplant. __ must be used routinely
Fill in the blanks
- Skin
- Sunscreen
T/F: Many medications that are used to prevent rejectioncan cause metabolic syndrome. These patients are among the highest risk for CVD
- True
T/F: Live vaccines can be given post-transplant
- False
T/F: Inactivated vaccines can be given post-transplant after 3-6 months
- True
What are the important vaccines for transplant recipients?
Influenza (inactivated, not live) anually
Pneumococcal vaccine in adults >= 19 years
* PCV13 first (if never received)
- PPSV23 at lleast 8 weeks later
- Subsequent doses of PPSV23 for adults at higher risk (5 years after the first PPSV23 dose)
Varicella vaccine
* Vaccine pre-transplant
- Vaccinate close contacts
- If a vaccinated household contact develops a rash, they are considered contagious, and must avoid contact with the transplant recipient and contact physician
- If the transplant patient develops a rash, they need to be seen right away
