Speaker 1 00:00 Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. And now Narrator - Dr. Abel 00:29 on to the show. Dr. Sean Kane 00:31 Before we get into this week's episode, we had one correction from Episode 23 published on March 16, 2015 around 24 minutes into the episode, you'll hear us talk about the Viekira pack, which is a combination product for hepatitis C. We incorrectly say that it is two tablets in the morning, one tablet at night. In actuality it's three tablets in the morning, one tablet at night. And the confusion comes because one of the tablets, which has three active ingredients ombitasvir, paritaprevir and ritonavir, you take two of those tablets every morning. The other active ingredient, dasabuvir, you take once in the morning, once at night, equating to three total tablets in the morning, one tablet at night. And now on to the show. Welcome to HelixTalk. Episode 26 I'm your co host, Dr. King, I'm Dr. Schuman, and I'm Dr. Patel, and today we're actually discussing six pivotal drug classes that have come out in the past 20 years. And we actually did this separately, and we're combining our ideas together, but we had some ground rules in creating this activity for the podcast. Speaker 2 01:36 So I think what we looked at is we stated we're going to stick within the past 20 years to really make sure that this was a more recent update to the so that we're not just going back and saying, let's talk about lithium a little bit or something a little bit new in the 70s, right? Speaker 3 01:50 And then we're just going to reflect upon what the current usage of that medication is now, at this point, versus, you know, when they came out, newly in the market, too. Dr. Sean Kane 02:00 For those of you who don't know, we use a shared Google document to kind of plan some of these podcast episodes. So another ground rule is that we couldn't duplicate each other's ideas. So it was kind of first come, first serve to whatever drug class we were passionate about. Speaker 2 02:14 Yeah, there was actually one that I was looking that I was looking to kind of do, and it looks like Dr. Kane already laid claim to one of those, so we'll see. But that's all right, I had to kind of move on and stick to a couple different areas. Dr. Sean Kane 02:25 Then on top of that, we've already talked about a few newer drug classes, specifically the agents for hepatitis C and the novel oral anticoagulants that I think we all kind of agreed were paramount or pivotal drug classes, but because we've already reviewed those in episode three and episode 23 we thought maybe we'd kind of think beyond those two drug classes. Speaker 3 02:47 All right, so let's get started with this interesting episode. Dr. Sean Kane 02:50 So Dr. Schuman, why don't you start us off with your first drug or drug class that you think has changed clinical practice dramatically since its inception from as early as early as 1995 Speaker 2 03:01 All right. So the first one I'm going to look at is the class of medications known as the Alpha One A antagonist. So the first one of those being Flomax or tamsulosin. I think part of this too is during my formative years, is when this drug was first coming on the market, as it approved in 97 so we started to first see some of those when you think about direct to consumer advertisements so very influential, but this is a class. So we had older medications for treatment of BPH or benign prostatic hypertrophy or hyperplasia. We had medications like prazosin, doxazosin or terazosin, which were commonly used to treat those symptoms. Because what it is we have these alpha one receptors, both on our vasculature as well as within the smooth muscle of the urethra and then the prostate. So we have these old alpha blockers. Problem with them is there was a fair amount of orthostasis, hypotension, dizziness that was seen with them. So you had to be really careful about dosing those medications. Dr. Sean Kane 04:02 And kind of interestingly, if you think about FDA approval of some of those older medications, they're actually FDA approved for hypertension in addition to their BPH control. It was almost as if they were taking advantage of that side effect. And conversely, they were also used in people who had hypertension, and BPH was kind of a two for one deal. But it turns out, based on the ALLHAT trial, maybe that wasn't such a good idea, where some patients actually progressed to heart failure, more commonly than some of our other antihypertensives, so really, those are kind of off the table, if you will, in terms of an antihypertensive anymore, right? Speaker 2 04:35 So what they did is, based upon all those concerns, they went ahead and said, Well, let's look at specifically, are there types of receptors? And what they found is that there was this alpha one, a receptor that was mostly found within the smooth that smooth muscle in the prostate and the urethra, and really not in the vast vessels as well. So therefore, you could get a little bit more of just the effect on BPH and less. Less of the overall issue about hypertension or hypotension. So the good of it is they may not have the blood pressure, but fewer Dr. Sean Kane 05:06 side effects. So Dr. Schumann, I know that with some of the older agents like Cardura or doxazosin as an example, the titration schedule for those agents was fairly strenuous and that you started at a fairly low dose, and the whole point of that was to make it so the patient wouldn't get the hypotension and orthostasis and things like that. Is that as big of an issue with tamsulosin under Flomax? Speaker 2 05:30 That's a great concern or question. That's one of the things they said, Is this is one that, if you will, right out of the box at a point four milligram, which is the lowest dose it comes in, that you start that dose, and you can immediately get some of that effect. And since it doesn't, it doesn't seem to be as likely to cause the hypertension. You don't need to go up on the dose. You can get that immediate effect on BPH at that point, four milligram dose. And furthermore, then you can go up to a point eight milligram dose as tolerated. And really the only thing in the packaging, so the only information they really give on blood pressure would be that if you were to stop the drug and you were at the point eight milligram, you would want to go back and start again at the point four milligram. But you're talking about just doubling of the dose. So much, much, much less of that overall titration compared to those older agents. Speaker 3 06:20 And does it matter what time of the day you take this tonsilosin? I mean, if it's hypotension causing I would tell my patients to take it before bedtime or something like that, right? Speaker 2 06:30 And the one interesting about this that you have to be careful of is that the drug is very, very, very highly absorbed under fasting conditions, well over 90% so because of that, to really avoid the side effects, they've stated that you should probably give it about 30 minutes after meals, because there's an over when it's in that fasting state, about a 30% increase in bioavailability and 40 to 70% increase in the maximum concentration, or C max. So by giving it 30 minutes after eating, you can actually get a little bit of a lower overall exposure, and especially that peak, so that C max doesn't get as high, therefore you don't get as much of that risk of orthostasis. So it's one additional step to take to avoid that those side Dr. Sean Kane 07:15 effects, Dr. Patel or Dr. Sherman. Do you commonly see the 0.8 milligram dose, or are the majority of patients on just the point four? Speaker 2 07:24 I see, I always thought, in a practice, I see a fair number who were on the point eight. But we also see a lot since recently, I believe in 2008 they came out with a combination product. They also, when they combine it with five alpha reductase inhibitor as well. So you see some individuals that instead of going up, they combine it with a second class of medication, medication, rather than go up on it. Although I actually do have a few patients who are on both, including the maximum dose of this. But now you know, some patients progress to the point eight, and some go on to a second class of medication. Dr. Patel, any comments? Speaker 3 07:58 Mostly, I've seen patients on point four milligrams daily. Then if they return and still complain of those symptoms of urinary retention, then they'll go ahead and increase the dose to point eight. But mostly I've seen point four milligrams in there. Dr. Sean Kane 08:10 I would agree with that with my practice too. I see pretty rarely point eight. I think point four is pretty common, and it seems to be a pretty effective dose, but I know that there are certainly patients that will get that double dose sometimes too. So moving on, Dr. Patel, how about you throw out your pivotal drug class that you'd like to talk about next? Speaker 3 08:31 So the one that I chose was the TNF blocking lesions or TNF inhibitors. This class of drugs started becoming available in the market, I would say, from 1998 unbreal and by McCabe were the first product. However, I'm going to focus a little bit more on kimira. The generic name is Ali mumab, which was approved in 2002 and it's manufactured by FB. Collectively, most of the side effects, the warning, the precautions that go behind, as well as monitoring parameters that go behind that these medications are common, so we'll go over them as well. But there is something special about HUMIRA that I would like to share and tell you why it's more prevalent in the market and has the highest market share of all the TNF inhibitors out there. So I kept on mentioning what TNF inhibitor is. It's basically a monoclonal antibodies, and it's basically blocks the tumor necrosis factor, which is responsible for multiple of an autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, psoriasis, ankylosing spondylitis, etc. It's a whole gambit of autoimmune diseases that these medications are developed for. Dr. Sean Kane 09:49 So because it's a monoclonal antibody, I would assume it's not an oral formulation. Speaker 3 09:53 You got that correct. So these forms are available in injectable forms. There are some that are IV infusions, and there are some that are. Are subcutaneous infusions. So if you think about subcutaneous infusions, that's something that the patients can't do it at home versus the IV infusions have to happen at either the hospital outpatient infusion centers or in the hospitals themselves. Speaker 2 10:14 Dr. Patel, I know when I look at this drug, and we have a few patients that we looked at using this or other monoclonal antibodies, and there's always this concern about, why do I have to have a TB test? Why is it so important? Speaker 3 10:24 So because these agents block the TNF inhibitor tumor necrosis factor has some modification on the immune cells as well. And there has been cases where there have been activation, or per se, reactivation, of the latent TB in this patients, and these patients, when they're taking such monoclonal antibodies, they are at high risk of infections in general, so there have been cases of reactivation of HPV as well. And that's why you're correct, Dr. Truman that before we start patients on these medications, we like to do a baseline evaluation of their TB and HPV status, and then, depending on the institution, there are some guidelines that says you need to continue monitoring these tests throughout the period of time too. Some treatments are periodic versus some treatments are chronic. So if they're chronic, obviously you want to go ahead and monitor these frequently. Dr. Sean Kane 11:19 That makes sense too, right? Because TNF alpha is utilized in a lot of different immune related functions. It's not just for rheumatoid arthritis, for example, it's a fairly non specific cytokine. So we can see everything from TB activation to other infections that are kind of latent, that just pop out, just because it's so non specific, right? Speaker 3 11:38 That is very correct. Other infections, such as upper respiratory tract infection, sinusitis, UTIs have also been noted in patients who are taking it because they're injectable. Patients have had issues with injection site reactions if there are IV infusions. In particular, people have also noted some sort of IV infusion related side effects as well. Again, these are monoclonal antibodies. So there are chances that our body, it's going to develop antibodies against these agents in itself. So people can also have issues with hypersensitivity reaction after following either the first dose or even the second dose of these medications. And Dr Dr. Sean Kane 12:19 Patel, I like that you picked HUMIRA as the kind of monoclonal antibody of choice for TNF alpha blocker compared to the other ones. One of the reasons is that it's a it's derived from human monoclonal antibodies, as opposed to a chimeric antibody, or even a murine or a mouse based antibody, which means that, because it's humanized, you're not going to have is frequent of the adverse effects that you'll see from A chimeric or any other monoclonal antibody. And because of that, I also think the brand name is kind of clever. It's human Humira, which is another way to remember the derivation of the monoclonal antibody too. Speaker 3 12:56 Yeah, that's actually a really good hint, and they definitely did a good job picking this brand name. This drug came out in 2002 and Abbott did a really good job advertising it for the very long time. You know, obviously monoclonal antibodies take a lot of mullahs to make, and therefore the medications are very expensive for patient. And Abbott actually had a really good philanthropic arm, where patients who could not consume all the other therapy, or could not tolerate any other therapy, but wanted to be or needed to be, on these medic in particular, humera, they actually created a program, patient assistant program, and they paid for their treatments as well. One additional thing I would like to throw in, along with the reactivation of certain infections. The other black box warning against these agents, it's also activation of T cell lymphoma, and it's more hepatosplenic in nature. And other condition, autoimmune condition, as well as demyelinating conditions such as multiple sclerosis, have also been noted lately, FDA has been also warning it's used against patients who have congestive heart failure, especially, you know, class three and four, this tends to be a contraindication for its use, and according to the Canadian label, however, us or FDA label just kind of says, Okay, watch out for, you know, if you are starting somebody on this medication, you might want to, you know, assess the progression of congestive heart failure symptoms, and do not try not to use it if patients already had a last stage of heart failure. Dr. Sean Kane 14:35 So I know that we briefly talked about kind of human Humira, the derivation of that monoclonal antibody. Are there any other differences between this in terms of adalimumab or Humira, versus any of the other anti TNF alpha agents on the market? Yeah. Speaker 3 14:52 So one striking difference is that HUMIRA is subcutaneous injection. It has a very long term. Like about two weeks. So instead of having to take an infusion or an injection every week, this is usually given on an every other week basis. So you're reducing the injection site reaction, you're reducing the number of frequency of injections as well. Another advantage point that himira has, because Abbott put a lot of money into clinical trials, and they've kind of looked at most of the autoimmune conditions, including some pediatric conditions like pediatric Crohn's or juvenile idiopathic arthritis. So there is a vast era of different indications that humera can pertain to a similar agent in this class is enriched. It's also subcutaneous. However, there's only three indications for that medication, versus 567, of them with HUMIRA. And so these are, like, probably the distinguishing points for HUMIRA that makes it a little bit more favorable. Dr. Sean Kane 15:57 And I guess we didn't focus a lot on it. But my impression, and I don't see a lot of rheumatoid arthritis. Is my impression is these TNF alpha blockers are dramatically effective for the disease state compared to what we had before they came out. Speaker 3 16:10 That's absolutely correct. And you know, because they come with all these side effects, we still want to be reserving them as a last line agent. We call them disease modifying type of agents, but, you know, you start out with the simplest forms of medication, such as, you know, try out the pain medications first, if that doesn't work, then you use methotrexate or hydroxychloroquine. And if that doesn't work, then you kind of progress to the injectable agents. Dr. Sean Kane 16:37 I think that meets my criteria for a pivotal drug class, and I would agree. So I'm going to jump in here with my pivotal drug class, and it's really focusing on one drug, and that's Viagra, or sildenafil. Speaker 4 16:51 It's the one you stole from me. I couldn't help first come first serve. First come Dr. Sean Kane 16:55 first serve. So the reason I picked this, it came out in March of 1998 came out with a big bang. It came out with a big bang. Part of it was that the treatments before this came out were really not very good therapies for erectile dysfunction. So the main agent before Viagra came to the market was called Alprostadil, and it came as two different dosage formulations. One was called Muse. This was a urethral suppository, so this had to be inserted into the urethra to have its effect. And this came out two years prior to Viagra, in 1996 the other version of Alprostadil is called Cav reject. And this is an intra penile injection that the patient will actually inject a syringe into them, into their penis to cause an erection. This came out in 1995 they both sound really painful. Yeah. So as you can imagine, there was a pretty steep, I wouldn't say, learning curve, but a lot of hesitation to use these two former agents. And really, just to give some background, the way that Al prostato works is it's a prostaglandin analog, so kind of like what we see with some of our pulmonary hypertension treatments, where they're prostaglandin analogs. It's a similar concept in that these agents have a localized effect. That's why you have to inject them or use a suppository for them to cause smooth muscle relaxation that increases blood flow to the penis and causes interaction. So you can imagine, in an oral formulation that comes out literally just a few years after Alprostadil came out, this is kind of a game changer. And sildenafil, or Viagra, was the first to the market. It was actually studied initially for hypertension and angina, and they found in phase one trials that it had this unique effect of prolonging an erection, and then, as opposed to treating hypertension and angina, so they really took it in a different direction when that kind of came out. So, you know, Viagra came out 1998 two other drugs that have come to the market, Levitra in 2003 Cialis also in 2003 and then finally, in 2012 an additional PD five inhibitor came out called Stendra. The generic is avanafil. So we have a couple agents to the market, but I kind of give credit to Viagra or sildenafil for being first to the market and really opening up this drug class of phosphodiesterase five inhibitors. Speaker 3 19:14 So how do the phosphodiesterase-5 inhibitors work? Speaker 2 19:19 It's my understanding. What they do is we have a different phosphate phosphodiesterases that work in very various organs of the body and the tissue locations. And so with PDE five, we know that that's involved in some of the musculature and the blood vessels within within the penis. So we know that with sexual stimulation, it leads to the production of nitric oxide, and then we have a cyclic GMP release, which then leads to vasodilation. And PDE five is one that degrades cyclic GMP there. And so a phosphodiesterase inhibitor is going to prolong the influence of cyclic GMP, thus you're getting more vasodilation. And then it's again. Allowing for that, for more blood flow. So it's not necessarily that it directly causes an erection, but allows for the body's natural processes. And so thus the ability to then take it and over time, then when your body's, you know, again, the natural signaling that occurs, and when the as they say in the commercial when the timing is right, you're then able to, maybe more easily produce and sustain the erection. Speaker 3 20:22 So when you talk about the timing, then it's probably taken just before the sexual activity, correct? Speaker 2 20:28 Again, I believe it generally depends upon the agent itself. So with Viagra, you can generally take it 30-60 minutes before sexual activity, and then both Viagra and Levitra or vardenafil last about four to six hours. Dr. Sean Kane 20:40 Then there's Cialis, which was a very, very close second for me in terms of the pivotal drug in this drug class. I gave it to Viagra because it came first. But Cialis is unique in that it lasts so long. So it has a very long half life. It lasts up to 36 hours, as opposed to four to six hours, which has kind of earned it the nickname The Weekender, as opposed to whatever they would call the little blue pill or something like that. It lasts a really long time. So in that respect, it's kind of more bang for your butt, because it does have such a prolonged duration of effect, right? Speaker 3 21:14 And these agents, you know, most of the ones that we discussed up until now, are taken just before the sexual activity. But I think Cialis has another formulation, which is a small dose that can be taken every day, Dr. Sean Kane 21:25 irrespective of sexual activity. So it's a scheduled dose. Many patients will say that's more convenient, because you never know when the time is right sometimes and to have it available all the time, you know certain patients may prefer that, just to give a nod to avanafil, their kind of claim to fame is quicker onset of effect. So if you look at the packaging for avanafil, they say 15 to 30 minutes, as opposed to 30 to 60 minutes before sexual activity. So if the timing isn't quite right, maybe avanafil would give you a quicker onset of effect. But clinically, I don't see much of avanafil at all, to be honest with you. The other interesting thing Speaker 2 22:01 that I've observed is we have some patients who, you know, end up with sexual sexual dysfunction due to other medications, and actually due to some of the medications that I'll discuss in my next kind of landmark class. But they found that these medications actually work sometimes, apart from any kind of physiologic concerns, which is just kind of interesting. So if there's a an erectile type of dysfunction or sexual dysfunction, essentially, either due to another medication or due to cotton mood, then these may still have some benefit there, which is owing to maybe some other effects on other type of other involvement of cyclic GMP and in other parts of the body. Dr. Sean Kane 22:38 So one big thing, and really important thing about all of the PD five inhibitors is that the way that they work? Again, it blocks the enzyme that breaks down cyclic GMP, and that cyclic GMP comes from nitric oxide. So if you have a patient that takes additional nitric oxide, or something that promotes nitric oxide, it can cause profound drop in blood pressure, because we get too much cyclic GMP that doesn't get removed from the body because phosphodiesterase five is inhibited. So thing any nitrate products? So nitroglycerin, isocorbide, dinitrate, isosorbide, mononitrate, you've probably heard in the commercials, don't take it with nitrates. Nitrates are those three agents. So if a patient takes it with the nitrate, they'll get a really precipitous drop in their blood pressure, and it depends on the half life of the PD five inhibitor, in terms of how long you have to wait between when you took your PD five inhibitor and when you can take your nitroglycerin product. Speaker 3 23:32 So it's about 24 hours for rigra and the Vitra and about 48 hours for CLS, because we know CLS has a longer half life, Dr. Sean Kane 23:39 and to kind of complicate matters a little bit. All of our PD five inhibitors go through the three a four pathway. So if you have a patient on, let's say fluconazole or amiodarone or some other three a four interacting agent, it really prolongs the effect of your PD five inhibitor, which could be a bad thing if you're relying on the packaging of this 24 or 48 hour time window to take a nitrate, it really should be prolonged if you are on an inhibitor like amiodarone as an example. Speaker 3 24:06 What are some of the other unique side effects of Viagra in particular? Dr. Sean Kane 24:10 So there's three main side effects that I think are worthy of mentioning to a patient that are common adverse effects. The first is flushing, facial flushing, dyspepsia, so kind of heartburn, like symptoms and then headache caused by the vasodilation. So those are, these are three relatively common side effects that a patient should probably know about. Speaker 2 24:31 I know in the form of the kind of rare concerning ones that every once in a while you hear about priapism being being of a potential concern. What exactly is priapism. Dr. shoeman, a pre appism would be an erection of the city commercial. If you have an erection that lasts more than four hours, consult a doctor. And I think sometimes that ends up being kind of a thought of, okay, that sounds kind of funny, you know, whether or not people consider that, you know, to be a real issue or not. But then it really can be a very painful and the pooling. Of blood in the penile tissue that can then lead to a necrosis. And so if that occurs, then they have to a lot of times surgically remove the blood to treat it. So that can be something very serious that is worth considering all jokes aside. And then furthermore, the potential for vision changes and loss due to potentially interaction with other PD and phosphodiesterases, I believe phosphodiestera Six. Speaker 3 25:23 And I've heard that the vision issue is that the vision can turn blue with Viagra, so that's why it's like a blue pill, blue vision, if you want to remember it that Dr. Sean Kane 25:32 way too. Yeah. And that's a lot more common with Viagra, which happens to have this PDE six inhibition, more commonly in terms of receptor affinity versus our other PDE, five inhibitors like Levitra, Cialis, so a little bit more common with Viagra, but definitely something that all patients should be told about before they pick up a prescription for this. Speaker 3 25:52 And as we mentioned earlier, the a prostadyl, which was a prostaglandin analog, which can be used for patients who have pulmonary hypertension. We do have another product of Viagra, same generic name. However, the brand name is rivashio, and that's also used for patients who have pulmonary hypertension. That was just Dr. Sean Kane 26:10 a side note. The same is true with Cialis or Tadalafil. We also have AD circa, which is also a product for pulmonary hypertension. And really interestingly, and I'm no lawyer, so I really don't understand it. The patent for the pulmonary hypertension version of Viagra is now generic, off patent, whereas Viagra, even though it came out earlier, is still on patent. So a patient can get a generic version of the 20 milligrams of Viagra, which is the pulmonary hypertension dose, but they are still stuck with the branded product for the erectile dysfunction drug of 2550 or 100 milligrams, which is really interesting and beyond my understanding of how the patent system works with that. So one last thing I wanted to focus on with Viagra is the direct to consumer advertising debate. And this is another reason why I thought it was a really pivotal drug classes, I think it really brought to the attention of mostly healthcare providers the risks and benefits of a direct to consumer advertising approach. And what that means is drug companies directly providing commercials to consumers, as opposed to advertising to healthcare providers. In some countries, that's not allowed, but in the US, it is allowed. And that, I think that that's a good discussion. Speaker 2 27:22 This was, again, another one of those drugs that you know, early on it was, it was on pens, and it's not commercial. You can hear even says, you know, talk to your doctor about it is bag or right for you. There's a lot of so that specific wording to get the individual to engage with the health care team, and that, you know, rather than you know, to give it to providers and allow those innovators to determine if their patients are Dr. Sean Kane 27:43 appropriate for it. There's all sorts of legal goofiness in terms of if you don't say what your drug product is for. So if you want to have a Viagra commercial of a guy in a fast car, and at the end it just says Viagra, you don't have to talk about the adverse effects or anything related to the medication, but once you say what the indication is for the drug, then you have to go through the entire tirade that is often the butt of many jokes, in terms of the priapism jokes, and, you know, all of the nasty side effects that potentially could happen and things like that. So the fact that a drug manufacturer could provide a commercial for a drug that says nothing about the drug, aside from the branding of the product, I think is an issue in terms of, I don't know that that's the right way to talk to consumers about medication, therapy. Speaker 3 28:27 Yeah, there is actually a whole department at FDA in Washington, DC that oversees the regulations of directed consumer products. That could be a TV commercial, that could be a handout, a poster, a tripod at your doctor's office, etc. So it has to be fair and balanced information. Otherwise the company cannot put out that information out to the public. Dr. Sean Kane 28:49 That department does not mess around. Because I know in pharmacy school, we talked about some examples of when the FDA cracked down on some of the advertising examples. And they could be very simple ones. I still remember one was for dutasterite or finasteride, and in the commercial, this guy had this big ball that he crushed with his hands, and the drug company got dinged on saying that the percent reduction of the ball that he crushed with his hands was not representative of the percent reduction of prostate size from dutaster rider finasteride. And for that reason, they had to pull the drug commercial. Drug commercial. Speaker 3 29:23 I do remember one of the adult medication that included a child actor and the TV commercial as well. And FDA came down on them and said, you have to remove the child actor and make commercial just as with adults, so you put out the right message that this medication is for adults and not for children. Unknown Speaker 29:40 And then there was another Speaker 2 29:41 interesting one. It wasn't necessarily one pulled by the FDA, but it was actually pulled by the company due to a bit of, I guess, consumer upheaval. Was a Seroquel ad that in a newspaper in Europe that actually had you had on an X axis, you had milligrams. On the y axis, you had free. And see a cause to mom. And then there was, again, kind of a minimalization of bipolar depressive symptoms and schizophrenia symptoms to just simply something that, you know, it's just leads to more phone calls back home. Dr. Sean Kane 30:12 So in planning this, you know, each of us came up with two different drug classes that we're fairly passionate about. We're already kind of past our mark in terms of timing. So we're actually going to cut it off for right now, and we're going to pick it up in Episode 27 with Part B, or the second part of our six pivotal drug classes in the past 20 years. So if you haven't done so already, please check us out in iTunes under HelixTalk, or visit us at HelixTalk.com we really appreciate five star reviews in the iTunes story, and we also really appreciate content suggestions from our audience in terms of what you guys would like to hear more of, or what we haven't talked about that you'd like to hear about. So with that, I'll sign off. I'm Dr. King, I'm Dr. Schuman, and Speaker 3 30:53 I'm Dr. Patel. Hope you enjoyed the episode and study hard. Narrator - Dr. Abel 30:57 Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at HelixTalk.com you.