Immunosuppresant Questions
A 21-year-old woman is admitted to receive a kidney transplant from her father. Since she has a low-tomoderate risk of rejection, she will receive induction with the antibody basiliximab. Which statement indicates the uniqueness of the therapy she is receiving compared with other antibody agents? A. Basiliximab is generally well tolerated and does not require premedications prior to administration. B. Basiliximab binds to CD52 and targets B and T lymphocytes. C. Basiliximab is used only in combination with antithymocyte globulin. D. Basiliximab targets B cells, not T cells.
Correct answer = A. Basiliximab does not require premedication since it is a nondepleting agent and would not be expected to cause cytokine release or infusion reactions. It can be used in combination with antithymocyte globulin, but most commonly it is used alone. Basiliximab binds to CD25 (not CD52) and affects T cells. It does not have any effect on B cells.
An 18-year-old woman who received a kidney transplant 6 months ago comes in to clinic complaining of facial hair growth and does not want to take an immunosuppressant anymore. Which treatment option would be the most appropriate to address her concerns? A. Switch cyclosporine to tacrolimus. B. Switch mycophenolate mofetil to sirolimus. C. Stop prednisone and add methylprednisolone. D. Switch mycophenolate mofetil to mycophenolic acid.
Correct answer = A. Hirsutism, or excessive hair growth, is a well-known adverse effect of cyclosporine. Many patients experience dark, coarse facial or body hair growth while taking cyclosporine. Switching cyclosporine to tacrolimus would eliminate this adverse effect and keep the patient on a calcineurin inhibitor that is effective in preventing rejection. Mycophenolate and prednisone are not known to cause hirsutism.
Which statement is correct regarding the difference between induction immunosuppression (IS) and maintenance IS? A. Maintenance IS is less important than induction IS for long-term graft survival. B. Induction IS is more intense than maintenance IS. C. Maintenance IS includes lymphocyte-depleting antibodies, while induction IS does not. D. Induction IS increases the risk of infection, while maintenance IS does not.
Correct answer = B. Induction IS is more intense than maintenance IS, as it provides IS during the intraoperative and early postoperative period to combat the body's initial immune response to the transplanted graft. Both maintenance and induction IS are important for the long-term survival of the graft. Lymphocyte-depleting antibodies are used as induction IS and not as maintenance. Although induction IS is more potent, all IS (both induction and maintenance) can increase the risk of infection.
Which drug specifically inhibits calcineurin in the activated T lymphocytes? A. Basiliximab B. Tacrolimus C. Sirolimus
Correct answer = B. Tacrolimus binds to FKBP-12, which, in turn, inhibits calcineurin and interferes in the cascade of reactions that synthesize interleukin-2 (IL-2) and lead to T-lymphocyte proliferation. Although basiliximab also interferes with T-lymphocyte proliferation, it does so by binding to the CD25 site on the IL-2 receptor. Sirolimus, while also binding to FKBP-12, does not inhibit calcineurin. Mycophenolate mofetil exerts its immunosuppressive action by inhibiting inosine monophosphate dehydrogenase, thus depriving the cells of guanosine monophosphate, a key precursor of nucleic acids.
A 45-year-old man who received a renal transplant 3 months ago and is being maintained on tacrolimus, prednisone, and mycophenolate mofetil is found to have increased creatinine levels and a kidney biopsy indicates severe rejection. Which course of therapy would be appropriate? A. Increased dose of prednisone. B. Treatment with rabbit antithymocyte globulin. C. Treatment with sirolimus. D. Treatment with azathioprine.
Correct answer = B. This patient is apparently undergoing an acute rejection of the kidney. The most effective treatment would be administration of an antibody. Increasing the dose of prednisone may have some effect but would not be enough to treat the rejection. Sirolimus is used prophylactically with cyclosporine to prevent renal rejection but is less effective when an episode is occurring. Azathioprine has no benefit over mycophenolate.
Which immunosuppressant medication avoids the need for therapeutic drug monitoring? A. Cyclosporine B. Tacrolimus C. Mycophenolate mofetil D. Sirolimus
Correct answer = C. Calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus) require therapeutic drug monitoring in order to maximize efficacy (prevent rejection episodes) and minimize toxicity (adverse effects). Mycophenolate mofetil is the correct answer since there is no role for routine monitoring with this medication.
Which combination of immunosuppressive drugs should be avoided? A. Basiliximab, belatacept, mycophenolate mofetil, and prednisone. B. Tacrolimus, mycophenolate mofetil, and prednisone. C. Tacrolimus, cyclosporine, and prednisone. D. Tacrolimus, sirolimus, and prednisone.
Correct answer = C. Tacrolimus and cyclosporine are both calcineurin inhibitors and have the same mechanism of action. Immunosuppressive drug regimens should work synergistically at different places in the T-cell activation cascade. Additionally, cyclosporine and tacrolimus are both extremely nephrotoxic and when used together would cause harm to patients. All of the other combinations are reasonable.
A 39-year-old man is admitted 3 months after liver transplant with increased liver function tests. A liver biopsy is performed and the results show acute rejection, severe. The team decides to start treatment with antithymocyte globulin, rabbit. What additional drug therapy is required for appropriate administration of this medication? A. No additional medications are required. B. Diphenhydramine, acetaminophen. C. Diphenhydramine, ketorolac, corticosteroids. D. Diphenhydramine, acetaminophen, corticosteroids.
Correct answer = D. Infusion-related reactions are common with the administration of anti-thymocyte globulins due to cytokine release. Common symptoms include chills, fever, hypotension, and pulmonary edema. Premedication with acetaminophen, diphenhydramine, and corticosteroids should be administered 30 minutes prior to the start of the infusion to prevent this syndrome. Although diphenhydramine and acetaminophen are correct, corticosteroids are also needed as premedication. Ketorolac is not the most appropriate for use as premedication for antithymocyte globulin.
Which clinical situation is least appropriate for immunosuppression with sirolimus? A. A patient with primary renal failure. B. A patient who has failed calcineurin inhibitors due to neurotoxicity. C. A patient who is 6 months postliver transplant and the incision site is fully healed. D. A patient with an abnormal lipid profile.
Correct answer = D. A patient with an abnormal lipid profile is a poor candidate for immunosuppression with sirolimus, since this medication is known to cause or exacerbate hyperlipidemia, particularly triglycerides and total cholesterol. A patient with primary renal failure would be a candidate for sirolimus, since it does not cause nephrotoxicity as calcineurin inhibitors do. It would be appropriate to switch a patient who has failed calcineurin inhibitors due to neurotoxicity to sirolimus for immunosuppression since it is not associated with that adverse effect. Sirolimus is known to impair wound healing, but a patient with a fully healed incision site could appropriately be placed on sirolimus.
Which drug used to prevent allograft rejection can cause hyperlipidemia? A. Basiliximab B. Belatacept C. Mycophenolate mofetil D. Sirolimus
Correct answer = D. Patients who are receiving sirolimus can develop elevated cholesterol and triglyceride levels, which can be controlled by statin therapy. None of the other agents have this adverse effect.