0:00 Microphenolate, properly known as microphenolate mofotyl, is an immunosuppress 0:15 ant. 0:15 Microphenolate is used in lupus nephritis and its first line, diffuse systemic 0:22 sclerosis. 0:24 But it's also indicated for the prophylaxis of organ rejection in patients 0:30 undergoing allogenic 0:31 renal, hepatic, or cardiac transplant. 0:37 In transplant patients, it is usually used in conjunction with interleukin-2 0:42 antagonist 0:43 cyclosporin or tachrolamus, as well as corticosteroids. 0:51 The active metabolite of microphenolate, microphenolic acid, prevents T-cell 0:56 and B-cell proliferation, 0:59 and the production of cytotoxic T-cells and antibodies. 1:03 Thus, microphenolate causes a rest of the cells at the cell cycle, because this 1:10 is how 1:11 T and B-cells proliferate. 1:14 So how does microphenolate actually disrupt the cell cycle? 1:21 Well, microphenolate works by inhibiting IMPD hydrogenase within the mitochond 1:33 ria. 1:34 Microphenolate has a preferential inhibition to IMPDH2, the rate limiting step 1:41 in the 1:41 denovial synthesis of guinine nucleotides from IMP in B and T lymphocytes. 1:50 Guinine is required in order to make DNA, RNA, and other proteins. 1:56 T and B lymphocytes require denovial production of guinine nucleotides in order 2:01 to make DNA, 2:02 and this is unlike neutrophils and other cells which can use preformed guinine 2:06 release from 2:07 the breakdown of preformed nucleic acids, and this is called the salvage 2:12 pathway. 2:13 Thus, microphenolate is selective for lymphocytes, causing a rest at the G1 2:19 checkpoint and no 2:20 progression to the S phase, where replication of DNA takes place. 2:27 Inhibition of IMPDH prevents T, and B-cell production and proliferation, 2:34 leading to immune 2:35 suppression, stopping the cell cycle. 2:39 Different side effects of microphenolate include myelosuppression, and this is 2:46 because other 2:47 blood cells use a cell cycle to proliferate, and so microphenolate can also 2:51 disrupt these 2:52 cells, leading to myelosuppression, increased risk of infection. 2:57 Important GI symptoms include diarrhea as well. 3:01 Another important point is that microphenolate can be stopped three months 3:06 prior to planned 3:08 pregnancy, without it causing any issues.
