Exam 4 Solid Organ Transplantation Flashcards
What two depleting antibody products can we use for induction?
Rabbit polyclonal antibody (Thymoglobulin) and alemtuzumab (Campath)
What two depleting antibody products can we use for induction?
Rabbit polyclonal antibody (Thymoglobulin) and alemtuzumab (Campath)
How do you administer thymoglobulin?
Administer with a 0.22 micron filter into a central vein. First dose over 6 hours, subsequent over 4 hours.
What are adverse effects of thymoglobulin?
Myelosuppression (leukopenia and thrombocytopenia dose adjustments), anaphylaxis, cytokine release syndrome, hypo/hypertension, tachycardia, dyspnea, urticaria, rash
What do we pretreat with when we administer thymoglobulin or alemtuzumab?
Acetaminophen, diphenhydramine, and steroids
What are the targets of thymoglobulin?
Many lymphocyte receptors – results in lysis and depletion
What is the target of alemtuzumab?
CD52 on T and B lymphocytes (also used for B cell lymphocytic lymphoma)
How do you administer alemtuzumab?
As a single IV dose
What adverse effects are associated with alemtuzumab?
Infusion related reactions (cytokine release syndrome, others), myelosuppression (leukopenia, thrombocytopenia)
What is the one induction agent that is nondepleting?
Basiliximab (Simulect)
What is the target of basiliximab?
The IL-2 receptor (CD25) on activated T cells. Prevents IL-2 mediated activation and proliferation.
How do you administer basiliximab?
Two doses IV over 30 minutes (central or peripheral)
What adverse effects are associated with basiliximab? What adverse effects are NOT associated with basiliximab?
Hypersensitivity reactions could occur. NO infusion related reactions (no cytokine release syndrome)
What adverse effects are associated with basiliximab? What adverse effects are NOT associated with basiliximab?
Hypersensitivity reactions could occur. NO infusion related reactions (no cytokine release syndrome)
What adverse effects are associated with basiliximab? What adverse effects are NOT associated with basiliximab?
Hypersensitivity reactions could occur. NO infusion related reactions (no cytokine release syndrome)
What are the three types of drugs that we use in combination for maintenance immunosuppressive therapy?
Calcineurin inhibitors, antiproliferative agents, and steroids
What are the three types of drugs that we use in combination for maintenance immunosuppressive therapy?
Calcineurin inhibitors, antiproliferative agents, and steroids
How do calcineurin inhibitors weaken the immune system?
The inhibit production of IL-2 and other cytokines, blocking T-cell proliferation.
How can you convert dosages of calcineurin inhibitors from oral to IV?
IV = 1/3 of daily oral dose
Which calcineurin inhibitor can be dosed twice daily in addition to continuous infusion?
Cyclosporine
How often are PO calcineurin inhibitor doses given?
Every 12 hours for IR; every 24 hours for ER
Which calcineurin inhibitor can be given sublingually by pouring capsule contents under the tongue?
Tacrolimus – q 12 hours
When should you draw a patient’s blood to monitor calcineurin inhibitor concentrations?
In the trough right before the next dose.
What electrolyte abnormalities can be caused by tacrolimus?
Hyperkalemia and hypomagnesemia
What is a primary reason we might try to hold back on calcineurin inhibitors?
Nephrotoxicity – dose and duration related
What is a primary reason we might try to hold back on calcineurin inhibitors?
Nephrotoxicity – dose and duration related
What metabolic side effects are associated with calcineurin inhibitors?
HTN, HLD, hyperglycemia
What neurogenic side effects can be seen sometimes with calcineurin inhibitors?
Tremors, HA, neuropathy in palms/soles, seizures
What cosmetic effects might become an adherence issue with cyclosporine? With tacrolimus?
Cyclosporine – gingival hyperplasia, hirsuitism (lots of hair)
Tacrolimus – alopecia (hair loss)
Name three drug classes that might increase serum levels of calcineurin inhibitors by inhibiting CYP enzymes.
Azole antifungals, macrolide antibiotics, calcium channel blockers, antiretrovirals, grapefruit juice
Name four drugs that might decrease calcineurin inhibitor serum concentrations by inducing CYP enzymes.
Antiepileptics (phenytoin, phenobartibal), antibiotics for TB (rifampin, rifabutin), St. Johns Wort
What courses of action can you take if a patient is on drugs that interact with calcineurin inhibitors?
Avoid combination, empirically increase or decrease calcineurin inhibitor dose, or monitor serum concentrations more closely and adjust as needed
What are the three most commonly used antiproliferative agents?
Mycophenolate mofetil, mycophenolate sodium, and azathioprine.
What is the target of the antiproliferative agents?
IMPDH, to decrease lymphocyte proliferation by decreasing nucleotide synthesis
Which drug has better graft survival rates–mycophenolate or azathioprine?
Mycophenolate
Which type of mycophenolate can be dosed IV?
Mycophenolate mofetil. Mycophenolate sodium is only PO because it is the enteric coated version.
What is the conversion between mycophenolate sodium and mycophenolate mofetil?
720mg mycophenolate sodium = 1000mg mycophenolate mofetil
What dose adjustment do you have to make for the antiproliferative agents to switch IV and PO?
No dose adjustment – same IV and PO
What adverse effects are associated with the antiproliferative agents (mycophenolate and azathioprine)?
Nausea, vomiting, diarrhea, anemia, leukopenia, and thrombocytopenia (bone marrow suppression)
Azathioprine only – hepatotoxicity, pancreatitis
What adverse effects are associated with the antiproliferative agents (mycophenolate and azathioprine)?
Nausea, vomiting, diarrhea, anemia, leukopenia, and thrombocytopenia (bone marrow suppression)
Azathioprine only – hepatotoxicity, pancreatitis
What does mycophenolate have a REMS program for?
To screen for pregnancy – potentially teratogenic
What major interaction is there between an antiproliferative agent and anti-gout agent?
Azathioprine and allopurinol interact – allopurinol inhibits an enzyme that metabolizes azathioprine, leading to increased active metabolites and risk of bone marrow suppression.
Empirically reduce dose of azathioprine by 50-75%
What two corticosteroids do we primarily use for maintenance therapy?
Methylprednisolone (IV) tapered to prednisone (PO)
What adverse effects from corticosteroids do we worry about?
HTN, HLD, hyperglycemia, osteoporosis, insomnia, mood swings, fat redistribution, thin skin, cataracts, increased appetite, weight gain, hirsutism
What mTOR inhibitors can we potentially use in place of calcineurin inhibitors for maintenance immunosuppression to avoid nephrotoxicity?
Sirolimus (Rapamune) and everolimus (Zortress).
How do mTOR inhibitors affect the immune system?
They inhibit response to IL-2 and the progression of the cell cycle.
Which mTOR inhibitor is dosed once a day? Twice a day?
Sirolimus is qd; everolimus is BID. Both PO although liquids available.
How do you determine the dose of mTOR inhibitors for a patient?
Go off of their trough serum concentrations.
How do you determine the dose of mTOR inhibitors for a patient?
Go off of their trough serum concentrations.
What adverse effects are seen with mTOR inhibitors?
Myelosuppression, HLD, high triglycerides, delayed wound healing (dont use right after surgery!), mouth ulcers, pneumonitis, rash, acne, diarrhea, arthralgia, proteinuria (monitor)
Same D-D interactions as CNIs
What costimulation blocker can we use instead of the calcineurin inhibitors?
Belatacept (Nulojix)
What does belatacept bind to?
CD80 and 86 on APCs, blocking the costimulatory signal
How is belatacept administered?
IV over 30 minutes. Dosed 10mg/kg weekly twice then biweekly until 16 weeks, then monthly.
What adverse effects do we worry about with belatacept?
Anemia, leukopenia, GI, fever, HA, HTN, potassium abnormalities, peripheral edema, cough, post-transplant lymphoproliferative disorder (PTLD) and progressive multifocal leukoencephalopathy (PML)
REMS program for PTLD and PML. (pts get these with others too though)
What cations interact with mycophenolate?
Iron, magnesium, aluminum. Also cholestyramine. Decrease absorption of mycophenolate – separate administration by 2-4 hours.
What types of rejection generally occur in the first three months after transplant?
Acute cellular and antibody-mediated (vascular or humoral rejection)
What is the goal of therapy for drugs used in a rejection?
To minimize the immune response and prevent irreversible damage to the allograft
What is the goal of therapy for drugs used in a rejection?
To minimize the immune response and prevent irreversible damage to the allograft
For what situation is IV immunoglobulin used?
Transplant rejection
For what situation are IV immunoglobulin, rituximab, and depleting antibodies all used?
Transplant rejection
What two viruses do we screen for and treat prophylactically in transplant patients?
CMV (cytomegalovirus) and herpes simplex virus
What two viruses do we screen for and treat prophylactically in transplant patients?
CMV (cytomegalovirus) and herpes simplex virus
What two conditions would put a patient at medium risk for CMV infection?
+/+ or -/+ (basically if the recipient is positive it is medium risk)
What three antivirals can we use to prevent CMV?
Valganciclovir (Valcyte), ganciclovir (Cytovene), and acyclovir (Zovirax)
What three PO antivirals can we use to prevent CMV?
Valganciclovir (Valcyte), ganciclovir (Cytovene), and acyclovir (Zovirax)
Duration dependent on risk – 3-6 months usually
Adjust dose for renal dysfunction
What two antivirals can we use to treat CMV?
Valganciclovir at higher dose or IV ganciclovir
IVIg may be added
Minimum 2 weeks therapy
Adjust dose for renal dysfunction
What bacterial infection do we try to prevent in transplant patients?
Pneumocystis pneumonia (will present with respiratory symptoms and fever)
Name the drug of choice for preventing pneumocystis pneumonia infection and a backup option in case they are allergic to sulfa. What do we do for treatment?
Sulfamethoxazole/trimethoprim (Bactrim DS)
Backup: Dapsone, pentamidine, atovaquone
Treatment – same except higher dosages and different dosage forms.
Name the drug of choice for preventing pneumocystis pneumonia infection and a backup option in case they are allergic to sulfa. What do we do for treatment?
Sulfamethoxazole/trimethoprim (Bactrim DS)
Backup: Dapsone, pentamidine, atovaquone
Treatment – same except higher dosages and different dosage forms.
What is the ideal diagnostic test to check for herpes simplex virus?
HSV DNA by PCR
What do we check to determine the risk of herpes simplex infection in a transplant patient?
Serostatus of recipient
True or false: The agents we use to prevent CMV are the same as the agents we use to prevent herpes simplex virus infection.
True – both can be prevented with valganciclovir, ganciclovir, and acyclovir
True or false: The agents we use to treat CMV are the same ones we use to treat herpes simplex virus.
False – we use acyclovir, famciclovir, or valacyclovir to treat herpes simplex, but only valganciclovir or gancyclovir for CMV (look for “gan” in the ones to treat CMV)
True or false: The agents we use to treat CMV are the same ones we use to treat herpes simplex virus.
False – we use acyclovir, famciclovir, or valacyclovir to treat herpes simplex, but only valganciclovir or gancyclovir for CMV (look for “gan” in the ones to treat CMV)
What is the most common invasive fungal infection in solid organ transplantation?
Candida
What symptoms should clue you to look for candida infection?
Candidemia, UTIs, pulmonary symptoms.
What symptoms should clue you to look for candida infection?
Candidemia, UTIs, pulmonary symptoms.
What symptoms should clue you to look for candida infection?
Candidemia, UTIs, pulmonary symptoms.
What is one big issue with prophylactically giving agents against candida?
Most antifungals have drug interactions with immunosuppressants. Prophylaxis is controversial, but 14 days at least if it is done.
Name three drugs we can use to treat candida.
Fluconazole, itraconazole, voriconazole, posaconazole, capsofungin, micafungin, amphotericin B, anidalafungin
Name three drugs we can use to treat candida.
Fluconazole, itraconazole, voriconazole, posaconazole, capsofungin, micafungin, amphotericin B, anidalafungin
What viral infection can be a problem in kidney transplant recipients, but is not treated prophylactiacally?
BK virus
Which tract does BK virus lie dormant in after childhood infection?
Genitourinary tract
How do we screen for BK virus?
Test urine or blood for BK by PCR; biopsy for nephropathy detection. Sccreen routinely!! Monthly or every other month for the first year, especially kidney transplant.
What agents can we add to treat BK virus?
Leflunomide, ciprofloxacin, IVIG
What agents can we add to treat BK virus?
Leflunomide, ciprofloxacin, IVIG
What vaccinations are acceptable pre-transplant?
All – try to complete vaccination series and boosters early in disease and before transplant
What vaccinations are acceptable post-transplant?
Annual injected influenza vaccine, pneumococcal vaccine
NOT MMR, varicella, or nasal influenza
What vaccinations are acceptable post-transplant?
Annual injected influenza vaccine, pneumococcal vaccine
NOT MMR, varicella, or nasal influenza
What medications can contribute to HLD post transplant?
Cyclosporine, tacrolimus, sirolimus, and prednisone
What can HLD post transplant do?
Cause cardiovascular diseases and aid chronic allograft rejection
What do we do to treat post-transplant HLD?
Statins, lifestyle modifications, immunosuppressant adjustment
MONITOR: myopathy and drug interactions
What causes contribute to post-transplant HTN?
Steroids, calcineurin inhibitors, kidney dysfunction, vascular compromise
What do we do for post-transplant HTN?
Home monitoring! Lifestyle modifications, immunosuppression switch (cyclosporine to tacrolimus), antihypertensive meds (NOT ACE/ARB/CCBs like diltiazem, verapamil –> hyperkalemia risk)
What antidiabetic drug should be avoided in new-onset diabetes after transplantation?
Metformin – raises serum creatinine.
How can we treat post-transplant new onset diabetes?
Same as regular diabetes – monitor HgbA1C q3mos, lifestyle modifications, oral meds and/or insulin, modify immunosuppressants.
What can we do for post-transplant patients who develop gout?
Increase steroid doses, give colchicine especially if already issues with mycophenolate, AVOID NSAIDS (nephrotoxicity), give allopurinol, febuxostat (watch azathioprine interaction)
Adjust doses for renal function
What causes contribute to the development of post-transplant osteoporosis?
Calcineurin inhibitors, steroids, kidney and other organ dysfunction, age, post-menopausal, others
How can we treat post-transplant osteoporosis?
Assess pre-transplant, exercise, calcium and vitamin D supplements, bisphosphonates (consider kidney function!), immunosuppressant modifications.
How can we treat post-transplant osteoporosis?
Assess pre-transplant, exercise, calcium and vitamin D supplements, bisphosphonates (consider kidney function!), immunosuppressant modifications.
What tweak can we make to immunosuppressant drugs to lower the chances of post-transplant malignancy? What is another big prevention strategy?
Change from a CNI to sirolimus b/c antineoplastic properties.
Surveillance and prevention key!! suncreen, smoking cessation, etc.
What tweak can we make to immunosuppressant drugs to lower the chances of post-transplant malignancy? What is another big prevention strategy?
Change from a CNI to sirolimus b/c antineoplastic properties.
Surveillance and prevention key!! suncreen, smoking cessation, etc.
What virus is associated with post-transplant lymphoproliferative disorder (PTLD)?
Epstein-Barr virus
What virus is associated with post-transplant lymphoproliferative disorder (PTLD)? What induction agent?
Epstein-Barr virus and polyclonal anti-lymphocyte antibodies are both associated with PTLD
Highest rate in first year post-transplant
What is the biggest prevention strategy for PTLD? What is another unusual cancer option?
Minimize immunosuppression, can use rituximab (anti B cell antibody).
Also surgical resection, local irradiation, and chemotherapy
Besides PTLD, what type cancer is more common in transplant patients?
Skin cancer – basal cell, squamous cell, Merkel cell, Kaposi’s, and melanoma all more common.
(Sirolimus decreases incidence!)
As pharmacists, what are two big things we can do for transplant patients?
Identify and address nonadherence risk factors; provide updated medications lists to every patient
As pharmacists, what are two big things we can do for transplant patients?
Identify and address nonadherence risk factors + provide updated medications lists to every patient
As pharmacists, what are two big things we can do for transplant patients?
Identify and address nonadherence risk factors + provide updated medications lists to every patient
What three classes of OTCs are we cautious about in transplant patients?
NSAIDS – decreased kidney blood flow
Decongestants – increased blood pressure, effect on kidneys and cardiovascular system
Herbals – increased or decreased CNI or mTOR serum concentration
