A 62-year-old woman is admitted to the hospital for a living-donor kidney transplant. She has a history of end-stage kidney disease due to diabetic nephropathy and has been undergoing hemodialysis for the last 2 years. The transplant surgery is performed without complication, and the patient demonstrates good urine output afterward. To help prevent rejection, she is given a medication that inhibits the conversion of inosine monophosphate to guanosine monophosphate primarily in lymphocytes, causing reduced proliferation of activated lymphocytes. Which of the following medications is most likely being used in this patient?

Question

A 62-year-old woman is admitted to the hospital for a living-donor kidney transplant.  She has a history of end-stage kidney disease due to diabetic nephropathy and has been undergoing hemodialysis for the last 2 years.  The transplant surgery is performed without complication, and the patient demonstrates good urine output afterward.  To help prevent rejection, she is given a medication that inhibits the conversion of inosine monophosphate to guanosine monophosphate primarily in lymphocytes, causing reduced proliferation of activated lymphocytes.  Which of the following medications is most likely being used in this patient?

Quizplus · Accepted Answer

11ec160b_3b71_d5ad_9249_bb04d98dcd15_MD0001_00 Mycophenolate is an immunosuppression drug used to prevent organ transplant rejection. It functions via the inhibition of inosine 5'-monophosphate dehydrogenase (IMPDH), an enzyme in the de novo purine synthesis pathway. The utility of mycophenolate as an immunosuppressant is aided by its relatively specific suppression of lymphocyte proliferation compared with other hematopoietic cell lines (eg, neutrophils, erythrocytes). This relative lymphocyte specificity is driven by 2 factors: Activated lymphocytes have a nearly absent purine salvage pathway and therefore are mostly dependent on de novo purine synthesis. Other hematopoietic cell lines have a more robust purine salvage pathway and can better compensate for inhibition of the de novo pathway. There are 2 subtypes of the IMPDH enzyme: Lymphocytes primarily contain type 2 IMPDH, whereas other cell lines contain a greater proportion of type 1. Mycophenolate binds to and inhibits type 2 IMPDH with a higher affinity than type 1. Common adverse effects of mycophenolate include lymphopenia and gastrointestinal disturbances (eg, diarrhea). (Choice A) Azathioprine produces active metabolites that inhibit an enzyme in the de novo purine synthesis pathway and also act as false nucleotides that incorporate into and disrupt DNA and RNA. Both the de novo and salvage purine synthesis pathways are disrupted, resulting in relatively nonspecific hematopoietic suppression. (Choice C) Prednisone and other glucocorticoids inhibit NF-kB to decrease the transcription of IL-2 and many other cytokines. These drugs have wide-ranging effects that suppress the function of all leukocyte cell lines. (Choice D) Sirolimus inhibits the mammalian target of rapamycin (mTOR) to interrupt IL-2 signal transduction and provide relatively specific lymphocyte suppression. (Choice E) Tacrolimus and cyclosporine inhibit calcineurin to block transcription of IL-2. These drugs provide relatively specific lymphocyte suppression and are the mainstay of therapy for preventing organ transplant rejection. Educational objective: Mycophenolate is an immunosuppression drug that inhibits inosine 5'-monophosphate dehydrogenase in the de novo purine synthesis pathway. It provides relatively specific suppression of lymphocyte proliferation, largely because activated lymphocytes lack an established purine salvage pathway that is present in other hematopoietic cell lines. __________ References: Mycophenolic acid formulations in adult renal transplantation-update on efficacy and tolerability. (http://www.ncbi.nlm.nih.gov/pubmed/19753127) Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis. (http://www.ncbi.nlm.nih.gov/pubmed/19307799)

A 62-Year-Old Woman Is Admitted to the Hospital for a Living-Donor