Hidden Gems, Part 2: How Generic Systemics Still Shine in Dermatology

[music] Welcome to season 2 of Derms on Drugs and Video Podcast brought to you by scholars in medicine the best educational platform at Dermatology and provided in no cost to medical providers. Derms on Drugs is where cutting edge dermis, midermis comedy. I'm Matt Zyres from Doc's Dermatology and each week I'm joined by my residency buddy Dr. DeLora Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh and we use our 60 years of combined derm experience to discuss debate and dissect the hottest topics in Dermatology. It's everything you need to know to be on it cutting edge derm and you'll actually have some fun listening. New episodes drop every Friday on scholars in medicine, Apple Podcasts, Spotify and other major podcast platforms and if you want to tune into the video component and have some of the key figures and tables from the articles that we talk about we are so excited to continue our discussion about drugs that are oldies but goodies with an oldie but goodie himself Dr. Scott Drew, Dermatologist practicing about an hour north of me here in Ohio who's been added in a big practice for decades. We are really going into when I say an oldie but goodie I mean a drug that is generic. So you're not supposed to have to do things like prayer osse for these drugs but unlike some of our modern drugs they do require some monitoring and have some real toxicities. Last week we did a really deep dive into method tricks eight and talked about a couple of other drugs. This week we're going to continue the discussion with some of our other favorite drugs that we use on the regular. So Scott, talk to us about Dapsone. Drug we've all used drug we you know I don't write a whole lot of Dapsone anymore but you know back when I was a resident we were using it to treat pydermagangarnosum and you know dermatitis or pedophormis and some other things as well. Tell us about first what diseases are you using Dapsone for the most? So I think Dapsone has a great place primarily in my practice. It's for Dermatitis or Pedophormis. I don't know what's unusual about central Ohio but you know there's this planet of the cave bear world of DH up here. Maybe it's the Amish pound cake and the bread and the icing and the beer. I don't know. People are planting a gluten full diet. Yes. You know somebody will want you know gluten free I went gluten filled but we definitely have a cohort and trying to try to eat a gluten free diet is very very good. Very very very difficult and and so you know there's family trans of it and we definitely have a cohort and I really think that's probably the drug I have had the most success with using. Sure. And of course it's it's my quote unquote Pimped question of pimping is not appropriate anymore but the one question I Pimped people on is how do you take care of. I think that people have been even when I have a medical student if you give them Dapsone inappropriately without a that a negative G6 PD and that you get this do I. What I thought you were just skin doctors so it I like it it brings to. Remembrance that we are physicians first and dermatologist let's let's Pimped and Ferris I think I know the answer. I think I know the answer. I can answer it on the boards. You give me a year and when you you know you never had a call from the are ever right especially if it's something that you. And one of the few drugs that's like a deal breaker you have to you you cannot get this prescription until I see the blood results because you know one dose of Dapsone and a G6 PD efficient person and they're in the ER and they're the color of your scrub top and that's not a good look. And then after that is the same time after about 10 days of of a Dapsone I usually start around 50 and titrate my up to 200. How do you tie trade up like 50 the first day or 50 for two weeks how you doing first two weeks and then you have to tell people they're going to drop a gram of hemoglobin because what ends up happening is they go to their OB-GYN or their or the research or whatever further next. Health their journey and they see a serial CBC and they're they've dropped a claim he dropped a gram of hemoglobin and next they're getting a bone marrow biopsy and blah blah blah blah. So after about three or four months that you'll recover about a half of that loss. So that's just a warning you have to have to let them know. But the result that they get is tremendous and the itch relief that they get is comparable to someone's RINVOC for AD. It's like miraculous. So let's only start live because one piece of pound cake or one beer and boom you know it's back perhaps not a severe if they're on 200 milligrams of Dapsone but they're you know a gluten free holiday. So Scott let's let's talk a little bit more about what you so you see somebody that you think's got DH right so you do a biopsy and a DIF maybe you order tissue transglutaminase and anti gladin antibodies whatever but along with ordering that stuff. Which those things looking more for celiac just greeting kind of for celiac but you know they've probably got celiac if they've got DH but so you order a G6 PD level glucose six phosphate dehydrogenase. You don't start the DAP zone till till that lab comes back sounds like you start people on 51 today. Do you tell them okay you're going to do 51 today for two weeks and if your itches completely better stay at that dose but if it's not you know then start taking two pills a day or what do you do. So like with all things the patients perception of better not better may not be the same as ours so I like to see him. And at least call and in the in the world of post covid you can always do this virtually if you have to like to see him and part of the whole DH phenomenon is don't really itch but then the secondary compulsive excoration so now are they itching because the DH is uncontrolled or because they have a tick they're just in this habit. And I think you can help you can help discern that with you know with some eyes on and I'll push the 200 and I've had very good success I'm trying to remember five years. So you do 50 haven't you see him back in two weeks or they call in two weeks if they're not dramatically better do you go to 100 and then give it two weeks and then go to 150 and give it two weeks and then go to 200 and give it two weeks. You go right from 50 to two like what do you do I say to get to 50 to 200 probably would take three months. Okay so like every every couple of week two three weeks or so you'll check in and and bump it up by another 50 if you need to. Yes. What are you what are you doing for labs? How are you monitoring labs for the. Just CBC I'm not back at the beginning we do a whole a metabolic profile liver enzymes all of that I don't do HIV and Hep C and all of that. Yes, I mean, it's impressive. Right. And just then file this. Now the G6 PD is only one time thing either you have it or you don't it's not something that wears out or you lose it or you somehow get it it's one and done. Yep. So you'll do how often you do the CBC's while you're taking. After the after the we get to 200 maybe every six months because the the effect on the on the on the anemic profile really doesn't have a additive dose related effect. Yep. And for what I remember as a resident for the first 12 weeks there's a risk of a granulocyteosis. And so for the first few months do you monitor like every couple of weeks do you do once a month for the first few months what do you do once a month. Well, I'm sorry baseline two weeks one month and then monthly after that. Okay and then once you get to a stable dose. You go to monitoring him a globin of matter crit say every six months or something like that. And even after that because the H is forever this is not like you're going to disease modify and then after that once a year. Okay. Do you are there other so right as I've some I had the other diseases I think of DAPS on is having people talking about using it. Nutrophilic dermatosis. And maybe erda carrier especially if you buy up here to carry in there a lot of neutrophils in it. I don't think I've ever seen literature that supports doing that but I know people talk about it. People have talked about using it in thermo hypersensitivity reaction. I I haven't used it in that setting. Are there other diseases that you anything else you use it for before I had gray hair. Thank you. I used it in Grover's disease, but I think there are better choices now that I would go to first such as. Oh, I would I would use dupexin. Yeah, what if you can't get the dupexin long I you called the dupe ex it a can't the lidic atopic dermatitis something like that. If you look hard enough you can probably find some AD I think in those patients. Okay. Yeah. I would eat with the with the um. With the approval of Pemphagoid there are plenty of people who argue that that that Grover's is a pre-bullus Pemphagoid cousin. So, I think you're okay with that. I have never I think my whole career I've only seen like a handful of. I'm glad to read a grain of some patients. So I really can't speak to how that is was or is used in that disease state But I know in the literature that's described as well Pat you first person I ever put on Dapsun was a young man who had PG and he got Pure motor neuropathy, which is like one of those things that you read about as a side effect and you're like Oh, that's just on the boards, but that was like my end of one experience So did it go away when we stopped the Dapsun? Yeah, okay Yeah, now I have like this little fear, you know your your first experience is what the drug kind of shape you but yes Pat and use much Dapsun for PG Yeah, I usually add it on just because it's an easy one I think it has some effects against the neutrophils as monotherapy. It's a little unusual sweets. I use it for a fair number of The mucus membrane panfogoid patients that you know Scarring or not. I mean I would strongly discourage using it as monotherapy and scarring. It's not an Aggressive enough drug, but the patients who have the sort of the erosive gingival MMP I think Dapsun is a good anti-inflammatory option and Obviously linear IGA the same thing just because of the effects it seems to have with IGA specific Diseases like DH. I think you can see a similar effect in linear IGA or IGA MMP I also think there's some role in yes and affiliate diseases. So, you know, he's an affiliate filiculitis Probably not hypereus and a philic syndrome per se Wells has had seen amazing Yeah, the couple cases of wells I've ever seen which there's also this one. It's like annular Yes, an affiliate dermatosis which I kind of think of as like a weird well-sished thing that's in circles I've had Dapsun work well in that and very and I often find that Dapsun will work really well at very very low doses Like you know once people are doing okay like 51 today long term I'm fine that it would work okay and That was my boredom on it Dapsun clears the flames that was how we remembered that I want to Laura mates made a comment that I think we all suffer this end of one fear and My end of one fears also a rare drug when I was resident I Had a neurotoxic patient on quell which I don't think anyone uses anymore and they were using it It's a nursing on patient that used quell BID for like 10 days and ended up in the in the what was then called the Like the memory unit we didn't it wasn't called that then but the stopping of the quell Return them to normalcy. What is quell? Skavies. Yeah, Skavies. Quell is the pre the precursor of Elimite, but it was the it's a neurotoxic anti-skabicide And thank you for amonnie me that You're your your intro about your six years of experience. I think when you had made now is now a century of I had written quell I same thing when I when someone mentions that it like just gives me Yeah Shudders. Yeah, yeah, okay. I look up the name of what the real name of quell is so that was Lynn Lynn Dane. Yes, yeah Nice pattern so remember they tried to bring that back for headlice Yeah, like we're like in the past 10 or 20 years. They've tried to bring back Lynn Dane for headlice I'm like and so and the rationale was because if you had it you would just keep using it all the time and The Houston more than once a week you get neurotoxic Huh, yeah, that can very rarely by the way happen with Ivermectin as well So I've remected in about one person and a thousand we have some kind of a genetic abnormality where they can get Some neurotoxicity not it's not dangerous or anything like that, but it it does happen With Ivermectin I've had that happen once and one of my Skavies patients So let's see what let's see if what are the drugs that we want to jump on here? Let's let's talk some about reflumalast we've mentioned it in a number of times here on the show Let's let's get into reflumalast a little bit more dr. Pat and I know you're a Big reflumalast user. I'm gonna let you kind of start us off with you know, what do you? What diseases do you use reflumalast for what's your you know, spiel with patients? How do you use it blah blah blah? I think of reflumalast as my methotrexate. I'll Almost always jump to reflumalast before I go to methotrexate Because it's you don't have to do the blood work It gets a little bit tricky counseling the patients on how to get it So wait wait, let me I'm gonna back up just a second earth dyspharolition or so reflumalast is an oral so you've probably heard of it as it's the active ingredient in Zorev topically, but it is a it's an oral PDE4 inhibitor Same class of drugs is a premalast just Signif much much more potent than a premalast in terms of how tightly it binds PDE4 The data on it. It's much more effective than a premalast for there's no head-to-head trial But just there as I head to head trial versus methotrexate and about 50% of patients got to pass in 90s Almost two thirds to 70% got to pass these 75 so a very effective drug for psoriasis So substantially more effective than a premalast And has the same side effect profile as a premalast GI Issues today significant headache and theoretical risk of depression But so think of it as generic A premalast generic otesla that is more effective probably we don't have a head-to-head So I don't want to say more of that probably more effective than otesla Based on the data we have so we'll level set there and Pad so just be what diseases do you use it in most frequently? I In GA it's kind of my first line. I like it for like annoyed LP. Yeah, both cutaneous and oral LP We talked about psoriasis HS I think it's a reasonable thing to dry. There's some data in HS and roflumalast I Think we did a paper with hand axima and roflumalast So let me show I mean it's just like it's like methotrexate I it really can work across a pretty broad spectrum of inflammatory disease It I think it should be first line for literally every inflammatory unless somebody has like some disease where you're like I need to Like pimpha, guess you're not gonna use it first line But everything else connective tissue disease Emitis dermatosis psoriasis hand exema HSPG Like GA like annoyed dermatosis Like in Plano pilot like everything it is The same benefits as otesla right non-emino-suppressive no labs Really easy drug to use cheap right and cheap So yeah, I will also say I use it for the patients who have like really bad Sebo psoriasis like like they're really bad like scouts bad their ears are bad You know particularly my patients who may have a hair type that they cannot wash the hair every day and it just keeps compounding I like it for that - yeah subgurms is Does it work for bichets I Would expect it to It's a great question. Life is FDA approved right? Yeah, the 500 microgram is So yeah, yeah, Patrick what do you talk to patients about get so right you're given this you're spiel with it for same shows of Tesla you might lose tools nausea You know if your mood changes let me know But then what what else how about getting the drug? How do you talk to them? Yeah, so either online through mark Cuban or use good rx Cuban's significantly cheaper. Yeah, so I really do say sign up It's easy like to sign up for that online mark Cuban cost cost cost Cost plus drugs which is it for for our listeners who are on modernizing medicine Emma that is in Emma as a pharmacy you can send to The 500 microgram is cheaper than the 250 it comes in both 250 and 500 micrograms So I do go with the 500 microgams and just like we do with a Tesla. I slowly ramp it up I do Monday Wednesday Friday for two weeks. I tell them if that's the dose that works that's your dose Then I go Monday through Friday and then I go day-on Okay, so Monday so Monday Wednesday Friday for two weeks then Monday through Friday Then every day, but if they get better on one of the lower doses Yeah, I'm just stay on the lower dose. That's interesting. I've usually done it as a half a pill a day For the first you know month two weeks to a month and then go up to a full pill a day Uh, I really wonder if there's a better GI profile doing You know 500 every other 500 Monday Wednesday Friday instead of 250 every day. Have you tried both pan? Yeah, and if you had to guess what percent of your patients get GI that is intolerable I'd say that yeah, I'd say the same with the 250 once a day. Ferris you use it much? I do same, you know kind of spectrum of disease like in like in planis Mostly it just psoriasis. It's one of my good and yeah like like annoyed drug eruptions from people and have it as to. Okay, do you do 500 when it was a Friday and then increase the days or you do 250. I say I'm writing it every day. It might upset your stomach. You might, you know, if you can only take it every other day, particularly for the first couple of months, that's totally fine. I'm a little less prescribed about it. That's actually really good because my experience has been that the people who get like meaningful GI, like get it at the low dose and then it doesn't ever go away. And the people who don't get GI never get it at all. So you're your way of doing it where I've tried taking it every day for stomach starts to bother you. Just take it a few times a week. You know, if it if your stomach gets tolerable, try taking it more. That actually makes a lot of sense for this truck. I might I'm a patent. What do you give it a try? Yeah, you're going to try that patent. I'm sticking with my plan. It's obviously the okay. So Scott, I love this. This is like I'm ready to go for hour three now. So Tim, is this your go to for GA and LP and LPP before rainbow? Oh yeah. So Scott, yeah, number one, it is safe, easy and cheap. And there's actually data that people in Reflume last live longer. They have better cardiovascular outcomes. People not ever flew malas. There's data that it makes young healthy people smarter because it has neuro protective effects. Like it's it's if you don't get the GI like it's a it's like I have a friend who had bad gingival hyperplasia that was idiopathic, you know, seeing an oral pathologist and I'd call phone, they could get him on a premalast like and I was like, Oh, let me call your oral pathologist. But I'm on Reflume last clear immediately. But he got bad GI and basically had to stop it because the after six months, he was still getting bad GI effects. But Tim, how long do you keep him on Reflume last for GA say general adult generalized GA? How long do you keep him on before you make a dose adjustment or switch? Yeah, if they got clear or if they didn't respond. Like you know, I yeah, I give it three months, you know, three months if they weren't seeing an improvement on the daily like if you could get them all the way to the daily dose and they were on it for three months and didn't respond. I move on. And if they do well, a bigger issue mad about older drugs as new drugs versus cost, because here to four up until three minutes ago, my my go to is Rinvo, which clears GA generalize adult GA like like a whiteboard. Yeah, but that's not cheap. And it's like we're flume alast is on mark Cuban's cost plus pharmacy. It's $6 a month for the 500 microgram dose cash. And it really is first line for anything that doesn't have a spectacularly effective drug, right? And even if something does have a spectacularly effective drug, you can start the reflumalast while you're trying to get this spectacularly effective drug covered. And you can add reflumalast on to anything like literally anything if they're doing okay. If we're working on these granular omnis things, there's no TB warning on this. No, it's a premalast. It is a premalast just more effective in $6 a month. Okay. And I think the Rinvo point is interesting talking about generic drugs because tofacitinib becoming generic. Is that going to be our next right? The next reflumalast. Just going to get them on. Yeah, because is this somebody off label you're using reflumalast your I'm sorry, you're sorry if you're using tofacitinib off label. But I think for people who have extremely recalcitrant diseases that have failed other stuff who have been well counseled once tofacitinib is generic. It will be like having I think it's good. I think it can replace prednisone. I think it can replace prednisone that we might use short term. Right? So for like two or three weeks of tofacitinib is definitely going to be safer than two or three weeks of prednisone. Right? Or you know, okay, we're going to put you on tofacitinib and transition you over to something else. But even long term, rather than you know trying to use off label, you know, Rinvoker, Abro, or Illumiant, it might be an option for people who, you know, we can't get better with other stuff. That's going to be when it goes generic, that's going to be really fascinating to see how we use it. Like really fascinating. All right, let's jump over to another drug seriotene. So acid treten. Right? I can probably career wise count the number of times I've written acid treten. Pat and Ferris, I think Scott probably writes a fair amount of it is the, is the, or at least has over the years. Pat and Ferris, you guys use much of it for skin cancer, prophylaxis, psoriasis, anything? I like acid treten. Like it's funny moving here. I feel like nobody, you know, you move to a new place and like I think we use some in Pittsburgh. So I was used to it and then people here didn't do it. I like acid treten. I like it for like pomegranate disease. That's, you know, like kind of like what we would call pomegranate or psoriasis, but maybe they only have hand foot disease. I feel like that does well on acid treten. So like carrot and derma, as I like it for that. Older people for psoriasis, particularly if they're going to do a little photo therapy or they're just out in the sun a lot. I like it for that. Do I use tons and tons of it? No, but it's been really, like I've had patients who have like pomegranate plant or either pomegranate postulosis or pomegranate psoriasis or this like weird like dyshydronic handex and it works well. A different blanket on the name of it, but there's a retin, there's a stomach retinoid approved for chronic handexema in Europe and Canada. What's that? No, it's not Targretten. And there's Alex retinone. Alex retinone. So yeah, for so, uh, Ferris, what's your normal? Do you ever go above 25? And I think of it is a poorly tolerated drug, meaning like hair loss, fingernail problems. I think people tolerate it fine at 10 milligrams, often at 25. Um, I have had people who do well on, I've never gone over 50 a day. I have some people who have done well on 50. It's, it's like kind of idiosyncratic how people respond. So some people lose hair. It's terrible. Some people get baby soft skin. Some people get like really dry skin. It's just, you can't predict it, but I'm not like really afraid of it. Obviously, I'd never put a woman of any child bearing potential on it, but other than that. And triglycerize, we gotta remember it's, it's my mind. I monitor triglycerides. I monitor AST and ALT. So Scott, how much acetretin have you used over the year? Um, a lot actually. Um, so back in the day, um, we had, uh, we just got to the academy for Poova Club. And there was, uh, this thing that Laura reference repoova, which was retinoids and poop it together, which obviously is no more. But I think, um, acetretin had a great place in the, uh, eithioseiform disease states. Um, yeah, it's true. Dariae's, Haley, Haley, it can be useful in both of them. And like, Lamella eithiosis. Lamella eithiosis. Yeah. Uh, it's really remarkable. Um, and then, um, I'm halfway between Cleveland and Columbus. And so I get the, um, the referral, the germ referrals from the transplant teams at both places. And back when we had these aggressive, um, uh, anti-rejection drugs for the solid organ transplant people, that was sort of the protocol back then, um, for chemo-prophylaxis against the development of scomasol carcinoma. I think there are the drugs that we use that, that our transplant folks use have less, um, risk than the ones that were, yeah. What, what's your normal? Would you echo what Laura said that 10 milligrams a day, rare to see A E's 25 milligrams a day starts to get to be hit or miss. What would you say? What I tell people who are transplant patients who are still on the older drugs is the dose of efficacy is the same as the dose of intolerability. And, um, uh, it was a, it was a, it was a difficult thing. And we were doing these crazy regimens. All right. Every, you know, four days on one day off or five days on one day off. We really, you really had to play with that dosing kind of like the way you play with airvage or adomzo to manage these people to develop efficacy and, and still be tolerable. I, I've often wondered about something like acid treten 10 milligrams a day as an anti-aging regimen, like a full body rent, you know, rather than doing treteno and, you know, once a day on your face, do acid treten 10 milligrams a day and you're retinoid in your whole body, right? I don't think so. It doesn't quite. I'm not seeing it from all the way. That's just, it would photo, you'd be photosensitized and losing hair. Yeah. You would look 10 years older than you. The alopecia is real. It's real. Do you ever see it at 10 or do you? Is it 10? A pretty safe dose. I feel like I see it more once I'm over 10. But there's also like once people get alopecia, they're freaked out and that's the end of it. I always say like if you got it, you could, it's not scarring alopecia. You stop. It'll grow back, but it freaks them out. Now I'm looking up. Is it hard to get? So I, yes, it is expensive. What in it is not cheap? It's not as cheap on cost plus drugs. There are Canadian farms, Do I prescribe to Canadian pharmacies? No, because that would be illegal and I would never ever do anything illegal So I don't but I tell patients that they exist and then I give them a written script and they can Facts their own script there and I have no idea. It's like I don't ask you. Did you go to Walgreens or CVS? I just write them a script and then they can send it to a Canadian pharmacy who can ship it to them at the risk of being pummeled here I am I recall the days when I had both Serietane and acutane samples in my closet You can just send them out like candy. It was before I pledged before the stickers It's just the roasts rep would come in and here you were and And so fairs you can't Getting a prior off is so looking it up on good our ex was I think of good our ex is a reasonable proxy for the actual cost of a drug 30 25 milligram pills is If you go to the right place about a hundred and forty bucks a month So if you did 25 every other day, it's 75 bucks a month. Do you ever try and get a prior off? Yeah, I will I will but like if I get denied and denied I mean I love it when I get denied for acetretten and then I get like sky-rizzy Yes, but yeah But yes, I I will certainly try to get it approved I'd rather go through the normal you know ways, but there are patients who are like this is just a pain and I you know It works like Haley Haley I agree. I've got some of those patients and it's been life saving for them Do you ever do you use it as add-on therapy to a biologic? Yeah? Definitely for some I'm more challenging psoriasis patients I think we're flumalized I think that is really We're much of the utility on a database of this conversations about what can we add on to a biologic? That is going to help us not switch and when I'm talking to residents or people who are like bio afraid I remind them that we as a profession are Adders and joiners. I mean polypharmacy is in our DNA No one writes monotherapy for acne unless it's acutane. No one writes Monotherapy in the old days for AD. We all had you know this our own little regimen so And there's no double-blind controlled studies on Trent no and Dr. Cycle and BPO right there You know the additive effect of all these things together. So that's an important thing to point the or younger All right, I'm gonna give a quick summary and then we're gonna go to Pat and Stryvia so Methatrix 8 very safe very very safe 10 milligrams once a week Broad spectrum drug make a ventilate probably not a whole lot of use for it these days cyclosporin works for everything But we try and keep the dose very low and might you really want to monitor creatinine blood pressure Then we get into talking about drugs like DAPSONE Very good for a few dermatosis Especially things that are neutrophil driven we get into reflumalast Good drug first line for literally everything inflammatory also very good option is add on therapy to anything Then we talk about Sarietane or acetretin Drug that probably gets underused nowadays, but can be a little bit difficult to get prior off still We're gonna now let's jump into what is usually everybody's favorite thing on the entire show Pat and Stryvia Dr. Scott here are the rules. We got to let Pat and finish reading the question as soon as he finishes reading the question You can shout out your answer. All right. That's it Pat are you ready what's our what do we got? All right Between cyclosporin metatrixate and mycophinalate morphotill Which medication does not use fungal fermentation as a step in its manufacturing process gotta be so this board Cell sept Scott you got to guess metatrixate Methatrixate Methatrixate is synthesized cyclosporin and mycophinalate still use fungal fermentation as the initial step cyclosporin they culture totally Pochaladium inflatum and that's what still makes cyclosporin Micotabolic acid it's Penicillium brevy compact them. Ha, so it sounds like the first one is an erectile dysfunction drug inflatum inflatum and the second one sounded like it was Well, that's what you take to reverse. That's how to compact them brevy compact them All right Next up a step. Let's move on please All right number two between cyclosporin metatrixate and mycophinalate morphotill which does not have an FDA indication for a dermatologic disease Mycophinalate Mycophinalate I heard it from Xyros first So mycophinalate got FDA approved to treat psoriasis in 72 and as Scott said earlier cyclosporin was approved in 19 I could actually knew that because it was approved in 72 for psoriasis and that was the same year The then governor of Maryland my home state Spiro Agnew came to my high school to like talk Before he went to jail, so yeah, wow and I was one so there you go All right final one which was discovered first Methatrixate cyclosporin or mycophinolic acid mycophinolic acid That is true. Yes, what you got a you got a Date you would guess me within 20 mycophinolic acid I would say 1934 It's crazy 1893 this Italian chemist isolated it thought it would be an effective vantibacterial and It's just kind of his experiment went on the shelf until it was rediscovered as an immunosuppressant medication Well, okay, it's good stuff All right, well Scott. I want to thank you for joining us. These have been a really fun two episodes Really enjoyed having your wisdom to help us out this week and so I also want to thank all of our listeners for joining us I hope you learned a few things hope to laugh once or twice Close to him open your plan and join us next week and until then I'm Matt Cyrus And I'm Laura Ferris and we are terms on drugs