31. Transplant & Immunosuppression Flashcards
Which types of cancer are normally suppressed by a healthy immune system, and are therefore higher risk in transplant patients who are receiving strong immunosuppressant drugs?
A. Lymphoma, osteosarcoma
B. Prostate cancer, breast cancer, cervical cancer
C. Osteosarcoma, melanoma
D. Melanoma, lymphoma
E. Liver cancer
D. In addition to the cancer risk, the skin of patients taking transplant drugs will burn more easily. Transplant recipients need to protect their skin from the sun.
Remember LIST for immunosuppression:
Lymphoma, Infection, Skin cancer, Tuberculosis
Sophia is an immunosuppressed transplant patient who requires a medication to prevent oral candida (thrush). Which of the following drugs should be recommended?
A. Valganciclovir
B. Acyclovir
C. Amoxicillin/Clavulanic Acid
D. Bactrim
E. Clotrimazole lozenges
E.
Select the blood types that a patient with type O blood can receive without suffering a rejection due to an incompatibility blood type match. (Select ALL that apply.)
A. Type A
B. Type B
C. Type O
D. Type AB
E. Any type blood is fine.
C.
Type O can only receive Type O. Type O is universal donor. Type AB is universal accepter.
SB is an immunosuppressed transplant patient who requires cytomegalovirus (CMV) prophylaxis. Which of the following would you recommend?
A. Fluconazole 200 mg daily
B. Ciprofloxacin 500 mg BID
C. Septra 1 Double Strength tablet three times a week
D. Valganciclovir 900 mg daily
E. Cephalexin 250 mg QID
D. Fluconazole covers fungal infections, ciprofloxacin covers bacterial infections, Septra covers pneumocystis infections, and valganciclovir covers viral infections (such as cytomegalovirus).
HSV, VZV coverage: acyclovir (Zovirax), valacyclovir (Valtrex), famciclovir (Famvir)
CMV coverage: ganciclovir (Cytovene), valganciclovir (Valcyte), cidofovir (Vistide), foscarnet (Foscavir)
A 55-year-old female patient received a kidney transplant. She required tacrolimus for chronic immunosuppression. The tacrolimus trough blood levels remained stable over several years. In the fourth year after transplant the patient expired from complications of an acute graft rejection. The hospital pharmacist reviewed the bag of medicines brought in from the home and found the following products: DHEA, women’s multivitamin, B vitamin complex and St. John’s Wort. What is the likely explanation for the acute graft rejection?
A. St. John’s Wort increased levels of cyclosporine due to enzyme inhibition.
B. St. John’s Wort decreased levels of cyclosporine due to enzyme induction.
C. St. John’s Wort decreased levels of cyclosporine due to enzyme inhibition.
D. DHEA increased levels of cyclosporine.
E. St. John’s Wort increased levels of cyclosporine due to enzyme induction.
B. St. John’s Wort induces many enzymes and cannot be used with transplant drugs, birth control pills, and other CYP 450 and p-glycoprotein efflux transporter substrates.
Calcineurin Inhibitors (CNIs): suppresses cellular immunity by inhibiting T-lymphocyte activation
tacrolimus (Prograft, Astagraf XL, Hecoria): Should be taken on empty stomach to avoid variability in absorption. Trough level dose depending on transplant type. SE: hypertension and nephrotoxicity, hyperglycemia, tremor, hyperkalemia, QT prolongation. IV:PO IR ratio is 1:4. This is a CYP 3A4 and P-gp substrate (watch for DDI)
cyclosporine (Neoral, Gengraf, Sandimmune): Boxed warning (renal impairment, lymphoma, skin cancer, infection, Gengraf and Neoral cannot be used interchangeably with Sandimmune which is non-modified). SE: hypertension, nephropathy, hyperkalemia, hirsutism, gingival hyperplasia, edema, hyperglycemia, QT prolongation. 3A4 and P-gp substrate (watch for DDI)
A patient is using cyclosporine and mycophenolate post heart transplant. What is the purpose of using immunosuppressants in heart transplant patients?
A. These drugs strengthen the transplant heart’s muscle walls.
B. These drugs stop viral pathogens from attacking the new heart.
C. These drugs lift depression when used concurrently; depression is common among transplant patients.
D. These drugs strengthen the immune system so that it can prevent an attack on the new heart.
E. These drugs weaken the immune system so that it will not attack the new heart.
E. Mycophenolate is a very common immunosuppressant drug used in combination with other immunosuppressants to prevent rejection of the transplanted organ. An impaired immune system necessitates infection control mechanisms, such as hand washing and staying away from sick people and crowds.
Antiproliferative Agents: inhibit T-lymphocyte proliferation by altering purine synthesis
mycophenolate (CellCept), mycophenolic acid (Myfortic): 1-1.5gm PO BID on empty stomach, these two agents are NOT interchangeable due to difference s in absorption. Boxed warning: Infection risk, lymphoma and skin cancer, congenital malformations (Pregnancy D)
SE: decreases efficacy of oral contraceptives, GI upset, diarrha, vomiting, hyper/hypotension, edema, tachycardia, pain, hyperglycemia, hyper/hypokalemia, hypomagnesemia, hypocalcemia, hypercholesterolemia, tremor, acne, infections
Which of the following drugs are used for chronic maintenance in transplant recipients? (Select ALL that apply.)
A. Azathioprine
B. Atgam
C. Everolimus
D. Steroids
E. Tacrolimus
A, C, D, E. Mycophenolate is also commonly used for maintenance with a calcineurin inhibitor.
azathioprine (Azasan, Imuran), Atgam (lymphocyte immune globulin), everolimus (Zortress, Afinitor), tacrolimus (Prograf, Astagraft XL, Hecoria)
Primary maintenance drug is a calcineurin inhibitor (tacrolimus is 1st line CNI, or cyclosporine) + an antiproliferative agent (mycophenolate is 1st line, or everolimus, sirolimus, belatacept or azathioprine). Can also add on steroids (typically prednisone). If patient is low immunologic risk, the steroids will be discontinued to reduce long term adverse effects. Attacking the immune system via multiple mechanisms through different drug classes is designed to both lower toxicity and to reduce the risk of graft rejection.
A patient received a liver transplant and is using mycophenolate mofetil. What is the brand name for mycophenolate mofetil?
A. CellCept
B. Sandimmune
C. Prograf
D. Imuran
E. Atgam
A. The brand name of mycophenolate mofetil is CellCept. Different salt forms are not interchangeable.
Sandimmune (cyclosporine, non-modified), Prograf (tacrolimus), Imuran (azathioprine), Atgam (lymphocyte immune globulin)
Antiproliferative Agents: inhibit T-lymphocyte proliferation by altering purine synthesis
mycophenolate (CellCept), mycophenolic acid (Myfortic): 1-1.5gm PO BID on empty stomach, these two agents are NOT interchangeable due to difference s in absorption. Boxed warning: Infection risk, lymphoma and skin cancer, congenital malformations (Pregnancy D)
SE: decreases efficacy of oral contraceptives, GI upset, diarrha, vomiting, hyper/hypotension, edema, tachycardia, pain, hyperglycemia, hyper/hypokalemia, hypomagnesemia, hypocalcemia, hypercholesterolemia, tremor, acne, infections
Sandra is a renal transplant patient who is doing well. It was discovered at her last clinic visit that Sandra did not receive theZostavax vaccine prior to transplant. Sandra is concerned because she has a friend in her transplant support group who is suffering with herpetic neuralgia since a shingles episode. Sandra would like to be vaccinated against shingles. Select the correct response:
A. Sandra cannot receive the shingles vaccine.
B. Sandra can receive the shingles vaccine, but it cannot be given in a pharmacy; she should see her doctor.
C. The pharmacist can administer the shingles vaccine.
D. Sandra should receive Varivax instead.
E. Sandra can receive the Zostavax vaccine but she will need to stop taking her immunosuppressant medications for 48 hours prior to the vaccination.
A. Transplant patients cannot receive live vaccines as they will not be able to halt replication; in other words, it would be similar to injecting them with active disease.
Live vaccines are an absolute contradinication in immunosuppressed patients!
Lynne is taking azathioprine and several other immunosuppressants to prevent rejection of a lung transplant. Which of the following medications can interact with azathioprine?
A. Torsemide
B. Allopurinol
C. Levothyroxine
D. Letrozole
E. Acetaminophen
B. Allopurinol will significantly increase the serum concentration of azathioprine. If the patient requires allopurinol therapy, the dose of azathioprine is lowered.
A patient picks up a prescription from the pharmacy for tacrolimus capsules. Counseling should include all of the following points: (Select ALL that apply.)
A. Take on an empty stomach (one hour before or two hours after meals).
B. You may experience headaches, nausea, diarrhea and/or tremor.
C. Your weight, temperature and blood pressure (and blood sugar if you have diabetes) should be monitored.
D. You are at risk for infection; report at once if you develop fever or feel weak and tired. This drug increases the risk of developing lymphoma.
E. Tacrolimus is also called Neoral. There is another formulation of this drug called Sandimmune. It is important to use the same formulation.
A, B, C, D. Tacrolimus (Prograf, Astagraft XL, Hecoria) has many side effects, including hypertension, hyperglycemia, hyperkalemia and hypokalemia, tremor, QT prolongation and nephrotoxicity.
Calcineurin Inhibitors (CNIs): suppresses cellular immunity by inhibiting T-lymphocyte activation
tacrolimus (Prograft, Astagraf XL, Hecoria): Should be taken on empty stomach to avoid variability in absorption. Trough level dose depending on transplant type. SE: hypertension and nephrotoxicity, hyperglycemia, tremor, hyperkalemia, QT prolongation. IV:PO IR ratio is 1:4. This is a CYP 3A4 and P-gp substrate (watch for DDI)
Cardiovascular disease is the most common cause of death in transplant patients because most of these drugs cause increase BP, blood glucose, cholesterol, and weight. And so CVD must be managed in these patients.
Which of the following drugs would be useful for prophylaxis for oral candida (thrush)? (Select ALL that apply.)
A. Fluconazole, taken by injection
B. Fluconazole, taken orally
C. Nystatin
D. Bactrim
E. Clotrimazole lozenges
B, C, E.
Choose the correct statements concerning cyclosporine and drug interactions. (Select ALL that apply.)
A. Cyclosporine is a CYP 450 3A4 substrate and will interact with 3A4 inducers and inhibitors.
B. Fluoxetine, paroxetine and fluvoxamine cannot be used with cyclosporine; use St. John’s Wort if an antidepressant is required.
C. A patient using cyclosporine should attempt to avoid other drugs that are nephrotoxic.
D. Do not ingest grapefruit or grapefruit juice if using cyclosporine or tacrolimus.
E. P-gp inhibitors will increase the cyclosporine concentration and p-gp inducers will decrease the cyclosporine concentration.
A, C, D, E. Cyclosporine is a CYP 450 3A4 substrate and a P-gp substrate. Many drugs can increase or decrease the levels of cyclosporine, and cyclosporine can increase levels of other drugs. Always check for drug interactions. Avoid grapefruit and St. John’s Wort.
Calcineurin Inhibitors (CNIs): suppresses cellular immunity by inhibiting T-lymphocyte activation
cyclosporine (Neoral, Gengraf, Sandimmune): Boxed warning (renal impairment, lymphoma, skin cancer, infection, Gengraf and Neoral cannot be used interchangeably with Sandimmune which is non-modified). SE: hypertension, nephropathy, hyperkalemia, hirsutism, gingival hyperplasia, edema, hyperglycemia, QT prolongation. 3A4 and P-gp substrate (watch for DDI)
Sophia is an immunosuppressed transplant patient who requires a medication to prevent pneumocystis jirovecii pneumonia. Which of the following drugs should be recommended?
A. Valganciclovir
B. Acyclovir
C. Fluconazole
D. Bactrim
E. Clotrimazole lozenges
D.
Pneumocystis pneumonia: CD4 < 200 cells/mm3
Toxoplasma gondii: CD4 < 100 cells/mm3
Mycobacterium avium complex (MAC): CD4 < 50 cells/mm3
Pneumocystis pneumonia: TMP/SMX 1 DS or SS PO daily
Toxoplasma gondii: TMP/SMX 1 DS PO daily
Mycobacterium avium complex (MAC): azithromycin 1200mg PO weekly (or 600mg PO twice weekly)
All of the following warnings apply to mycophenolate except:
A. Patients receiving immunosuppressive regimens involving combinations of drugs, including CellCept, are at increased risk of developing lymphomas and other malignancies, particularly of the skin.
B. Mycophenolate can decrease efficacy of oral contraceptives.
C. Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections and sepsis.
D. Patients using mycophenolate should be monitored for symptoms of leukocytosis.
E. This drug is Pregnancy Category D and can cause fetal harm when administered to a pregnant woman.
D. Monitor patients for leukopenia (low white blood cell counts) not leukocytosis (high white blood cell counts). Symptoms of infection could indicate a low white blood cell count. Patients should be seen right away if they experience symptoms of infection: fever, chills, sore throat, cough or unexplained bruising or bleeding.
Antiproliferative Agents: inhibit T-lymphocyte proliferation by altering purine synthesis
mycophenolate (CellCept), mycophenolic acid (Myfortic): 1-1.5gm PO BID on empty stomach, these two agents are NOT interchangeable due to difference s in absorption. Boxed warning: Infection risk, lymphoma and skin cancer, congenital malformations (Pregnancy D)
SE: decreases efficacy of oral contraceptives, GI upset, diarrha, vomiting, hyper/hypotension, edema, tachycardia, pain, hyperglycemia, hyper/hypokalemia, hypomagnesemia, hypocalcemia, hypercholesterolemia, tremor, acne, infections
Which of the following medications is a calcineurin inhibitor?
A. Sirolimus
B. Azathioprine
C.Mycophenolate
D. Tacrolimus
E. Basiliximab
D. Cyclosporine (Neoral, Gengraf, Sandimmune) and tacrolimus (Prograf, Astagraft XL, Hecoria) are calcineurin antagonists (blockers).
sirolimus (Rapamune) - mTOR inhibitor
azathioprine (Imuran, Azasan) - antiproliferative agent
mycophenolate (CellCept) - antiproliferative agent
basiliximab (Simulect) - IL-2 receptor antagonist
Which of the following are induction drugs given prior to graft transplant and are used to prevent acute rejection immediately following the transplant surgery? (Select ALL that apply.)
A. Adalimumab (Humira)
B. Antithymocyte globulin
C. Higher doses of the same drugs used for maintenance
D. Basiliximab (Simulect)
E. Etanercept (Enbrel)
B, C, D. Enbrel and Humira are not used for transplant rejection, although they are immunosuppressants. They are used for rheumatoid arthritis and occasionally for other autoimmune conditions.
Induction immunosuppressant therapy is given before or at the time of transplant to prevent acute rejection during the early post-transplant period by providing high degree of immune suppression. The most commonly used induction agent is basiliximab (IL-2 receptor antagonist of T cells). Higher risk patients may require the addition of the lymphocyte-depleting agent rabbit antithymocyte globulin (Atgam)
Afterwards, we switch over to a calcineurin inhibitor (CNI) at therapeutic dose. Tacrolimus is used more than cyclosporine.
A female patient with end stage renal disease secondary to hypertension has been using Fosamax, erythropoietin, cholecalciferol, cyclosporine, Coreg, prednisone and hydrocodone. Since she began taking this regimen she developed hypertension. Which of the medications could be contributing to increased blood pressure levels?
A. Prednisone, erythropoietin, alendronate, hydrocodone
B. Prednisone, erythropoietin, alendronate, cyclosporine
C. Prednisone, cyclosporine, hydrocodone
D. Prednisone, cyclosporine, cholecalciferol
E. Prednisone, cyclosporine, erythropoietin
E. Prednisone, cyclosporine and erythropoietin can all cause hypertension.
cyclosporine (Neoral, Gengraf, Sandimmune) - CNI
Patient counseling for renal transplant patients should include all of the following: (Select ALL that apply.)
A. Never skip or change your medication without approval from your healthcare provider; any change can cause your body to reject the transplant.
B. Protect and cover your skin from the sun. You will be more likely to burn. Do not use tanning booths.
C. Do not use acetaminophen for analgesia (pain) or for headaches. It is preferable to use an over-the-counter medicine such as naproxen.
D. Monitor your health at home and keep daily records of your blood glucose (if diabetes or if it has been high), blood pressure, temperature and weight.
E. Do not use live vaccines, and avoid contact with anyone who has recently received the oral polio or nasal influenza (flu) vaccine.
A, B, D, E. Do not use NSAIDs (if renal transplant) and do not use over-the-counter or herbal medicines without checking first with the pharmacist.
Cardiovascular disease is the most common cause of death in transplant patients because most of these drugs cause increase BP, blood glucose, cholesterol, and weight. And so CVD must be managed in these patients.
Higher risk of cancer in transplant patients because the drugs suppressive immune system which is involved in protecting use from lymphoma and skin cancer. Remember LIST (lymphoma, infection, skin cancer, tuberculosis)
Which of the following are correct brand names for everolimus? (Select ALL that apply.)
A. Afinitor
B. Rapamune
C. Zortress
D. Myfortic
E. Nulojix
A, C. The brand names of everolimus are Afinitor and Zortress.
Rapamune (sirolimus) - mTOR inhibitor
Myfortic (mycophenolic acid) - antiproliferative agent
Nulojix (belatacept) - mTOR inhibitor
Sandra is a renal transplant patient who is adherent with her medications and diet and physical activity regimens. She is doing well. The only current complications are anemia and elevated cholesterol levels, which are both being treated. A tuberculin skin test was ordered. The induration was 8 mm, which is positive for Sandra’s degree of immune suppression. The chest x-ray and signs and symptoms are all negative. Select the correct treatment option that should be added to Sandra’s medications at this time:
A. Atovaquone
B. Rifampin, Isoniazid, Pyrazinamide and Ethambutol
C. Isoniazid
D. Sulfamethoxazole and Trimethoprim
E. Valganciclovir
C. She will need to take pyridoxine (vitamin B6) with the isoniazid.
A patient has recently received a renal transplant. The clinical pharmacist that leads the drug management group in the transplant division will counsel the patient. First, general information regarding transplant medications will be provided. Which of the following are correct recommendations? (Select ALL that apply.)
A. It is important to get enough sunlight in order to feel good post-transplant. If you spend time in the sun longer than 2 hours, use a sunscreen of at least 30 SPF.
B. You will need to get your transplant drug levels in your blood monitored. The blood draw must be taken at the “peak” level, which is within 1-2 hours after you have taken your morning dose.
C. Do not make any medication changes without authorization.
D. On days when the level of the drug in your body is being measured, it is important to take your medication after you had your blood drawn (not before). It is important to measure the lowest (trough) level of drug in your blood.
E. Protect your skin from the sun at all times. You can burn more easily. And, transplant patients have a higher risk of getting skin cancer. Proper sun protection is essential.
C, D, E.
Cardiovascular disease is the most common cause of death in transplant patients because most of these drugs cause increase BP, blood glucose, cholesterol, and weight. And so CVD must be managed in these patients.
Higher risk of cancer in transplant patients because the drugs suppressive immune system which is involved in protecting use from lymphoma and skin cancer. Remember LIST (lymphoma, infection, skin cancer, tuberculosis)
Choose the correct statements concerning tacrolimus and drug interactions:
A. Tacrolimus is a strong CYP 450 3A4 inducer
B. Tacrolimus is a P-gp inducer
C. P-gp inhibitors will decrease the tacrolimus concentration
D. Tacrolimus is a CYP 450 3A4 substrate
E. Tacrolimus is a strong CYP 450 3A4 inhibitor
D. Tacrolimus and cyclosporine are both CYP 450 3A4 and P-gp substrates; it is important to use extreme caution with inducers or inhibitors. Inhibitors, including grapefruit, will increase the drug concentration and increase toxicity. Inducers will decrease the drug concentration and could result in graft rejection.
Calcineurin Inhibitors (CNIs): suppresses cellular immunity by inhibiting T-lymphocyte activation
tacrolimus (Prograft, Astagraf XL, Hecoria): Should be taken on empty stomach to avoid variability in absorption. Trough level dose depending on transplant type. SE: hypertension and nephrotoxicity, hyperglycemia, tremor, hyperkalemia, QT prolongation. IV:PO IR ratio is 1:4. This is a CYP 3A4 and P-gp substrate (watch for DDI)
Jasmine is a thin, white female patient. She has been using prednisone 10 mg daily for at least several months. The pharmacist understands the many risks are associated with long-term steroid use and scans the patient’s profile to check for this recommended agent:
A. An anticholinergic
B. A bisphosphonate
C. Estrogen
D. An acetylcholinesterase inhibitor
E. Progesterone
B. Long-term corticosteroid use depletes bone density. Bisphosphonate therapy may be recommended to preserve bone density. All patients receiving agents that weaken bone should have optimal calcium and vitamin D intake.
