Immunosuppressants
Mr William Short is a 27 year old stock clerk who you have been treating for the past 2 years after he was diagnosed with CHF caused by a viral cardiomyopathy. After being maintained on drug therapy for a year, Mr Short underwent a heart transplant procedure, and is now being maintained on an immunosuppressive drug regiment consisting of cyclosporine, azathioprine and prednisone. In addition, he is being treated with enalapril (an ACE-inhibitor) & hydrochlorothiazide diuretic, as well as valganaciclovir (an antiviral medication) to alleviate drug-induced side effects. Which drug in this regimen exerts its therapeutic effects by selectively interfering with activation of transcription factors involved in stimulating the transcription and production of IL-2?
cyclosporine
A patient on immunosuppresive therapy is given tacrolimus as part of their drug regimen. Which side effect is most likely to occur with this drug?
renal toxicity
A goal of the actue phase of induction immunotherapy following an organ transplant is to deplete circulating lymphocytes, which are the primary mediators of rejection. One drug that is commonly used for this purpose consists of a mixture of antibodies that bind to the surface of T lymphocytes and induce a cell-mediated and complement-induced cytotoxicity. Which of the following drugs has this mechanism of action?
antithymocyte globulin (ATG)
One of the drugs in Mr Hart's maintenance drug regimen increases the likelihood for renal toxicity, and should not be combined with other immunosuppressants that also have a high incidence of renal toxicity. Which drug is this?
cyclosporine
IL-2 is a cytokine that is produced by T cells, and also exerts autocrine effects to stimulate T cell replication. Which of the following agents is a selective antagonist for the IL-2 receptor expressed on the cell surface of T cells?
basiliximab
A patient was given a combination of immunosuppressant drugs following a liver transplant. Six months after his transplant his lab results indicate a 20 mm Hg increase in mean arterial blood pressure, elevated fasting blood glucose, hyperkalemia, and elevated serum creatinine. Which drug is most likely responsible for these side effects?
tacrolimus
Sometimes the level of immunosuppression achieved with a combination of a calcineurin inhibitor and an antimetabolite is not sufficient following an organ transplant. In this case adding an mTOR inhibitor can be beneficial because of their different mechanism of action, which can produce a synergistic effect. An example of this drug class is:
everolimus
There are several general principles that must be considered when designing an immunosuppressive drug regimen for a patient undergoing an organ transplant. Which of the following is a side effect common to all immunosuppressant drugs that limits the dosages that can safely used for long term maintenance therapy?
increased risk of infections and neoplasia
Patients who are taking allopurinol, or express a mutation resulting in a non-functional form of thiopurine S-methyltransferase (TPMT) can exhibit extreme bone marrow suppression and other forms of drug toxicity when exposed to:
azathioprine
One of the drugs Mr Short was taking to suppress organ rejection was azathioprine. Which of the following describes its mechanism of action?
conversion to 6 mercaptopurine, a purine antimetabolite toxic to stimulated lymphocytes
The maintenance dose of this immunosuppressant drug is typically tapered down over the first year of therapy because it can cause permanent side effects such as aseptic necrosis of femur heads, cateracts, and other serious side effects including hypertension, ulcers, diabetes & osteoporosis. This agent is:
prednisone
A prodrug that is converted to a metabolite that is a selective inhibitor of inosine monophosphate dehydrogenase, and is a selective inhibitor of lymphocyte proliferation. It can be combined with cyclosporine in kidney, liver and heart transplants. It has a relatively minimal toxicity apart from some GI effects.
mycophenolate mofetil