WEBVTT - Ep 167 Viagra/Sildenafil: Raising the bar 0:00:00.600 --> 0:00:06.760 Courage, something shared by countless Americans, those that risked their lives, 0:00:07.120 --> 0:00:11.280 those that battle serious illness. When I was diagnosed with cancer, 0:00:11.600 --> 0:00:14.720 I was primarily concerned with ridding myself of the cancer, 0:00:15.520 --> 0:00:19.440 but secondly, I was concerned about post operative side effects 0:00:19.720 --> 0:00:25.159 like a rectile dysfunction ED, often called impotence. You know, 0:00:25.280 --> 0:00:28.160 it's a little embarrassing to talk about ED, but it's 0:00:28.200 --> 0:00:31.600 so important to millions of men and their partners that 0:00:31.680 --> 0:00:35.000 I decided to talk about it publicly. And after all, 0:00:35.080 --> 0:00:38.839 it can be associated with many conditions, including prostate surgery, 0:00:39.040 --> 0:00:43.280 high blood pressure, diabetes, or even smoking. The point I 0:00:43.320 --> 0:00:46.080 want to make is that there are many treatments available 0:00:46.159 --> 0:00:49.559 for ED, so my advice is to get a medical checkup. 0:00:49.800 --> 0:00:52.680 It's the best way to get educated about ED and 0:00:52.760 --> 0:00:55.160 what can be done to treat it. It may take 0:00:55.160 --> 0:00:59.360 a little courage, but I've always found that everything worthwhile does. 0:01:45.760 --> 0:01:47.680 I mean, none of it was wrong. 0:01:50.920 --> 0:01:52.960 I love it. It's because it sounds more like a 0:01:53.000 --> 0:01:55.320 p s A than an advertisement. It does. 0:01:55.440 --> 0:01:57.360 It totally sounds like I mean, they don't even say 0:01:57.400 --> 0:01:59.960 the name of the medicine, right, but it's very under 0:01:59.960 --> 0:02:00.520 the radar. 0:02:00.840 --> 0:02:05.040 Uh huh. So that was from the infamous, really historic 0:02:05.360 --> 0:02:09.440 Bob Dole commercial from nineteen ninety eight. Bob Dol, Bob Dol. 0:02:09.240 --> 0:02:10.480 Bob Dol. Do you know that was one of my 0:02:10.520 --> 0:02:11.880 brother's first words. 0:02:12.320 --> 0:02:16.600 Was he born near like in the year leading up 0:02:16.600 --> 0:02:19.919 to a presidential election or what? I don't know. 0:02:20.320 --> 0:02:23.840 I just remember during the presidential election. I'm pretty sure 0:02:23.880 --> 0:02:25.880 it was my youngest brother. It might have not even 0:02:25.919 --> 0:02:28.839 been him, but sitting there saying Bob Dol, Bob Dol, 0:02:28.840 --> 0:02:30.520 Bob dol, So it could him been the one who 0:02:30.600 --> 0:02:32.200 was nineteen ninety I don't know. 0:02:32.360 --> 0:02:36.000 That's someone who's watching too much TV and too many 0:02:36.360 --> 0:02:38.079 political commercials, right. 0:02:38.400 --> 0:02:40.440 Bob Dohl, Bob Dol, Bob Dol. Anyways? 0:02:41.440 --> 0:02:46.240 Oh yeah, yes, Well, Hi, I'm Aaron. 0:02:46.000 --> 0:02:48.799 Welsh, and I'm Aaron on an update and this. 0:02:48.760 --> 0:02:50.280 Is this podcast will Kill You. 0:02:50.520 --> 0:02:53.760 And today we're talking about viagra. We are can we 0:02:53.760 --> 0:02:56.840 say trade names? We're talking about Sildena, Phil, We're. 0:02:56.680 --> 0:03:00.560 Talking about I mean, my part is mostly about biagra. 0:03:01.200 --> 0:03:06.960 Period Biographs is also not the first trade name that 0:03:06.960 --> 0:03:08.520 we would have said on this podcast. 0:03:09.120 --> 0:03:12.280 Launched the Whole Allergies episode talking about EpiPens, like. 0:03:12.520 --> 0:03:18.640 Yeah, exactly, epineph and auto injectors. Right, too much to 0:03:18.680 --> 0:03:23.480 say any episode, it's gonna be a great episode. I 0:03:23.520 --> 0:03:28.880 am so excited for this one. There's just it's a 0:03:28.960 --> 0:03:32.760 it's a rich topic. Yeah, who knew? Who knew? 0:03:33.320 --> 0:03:33.720 Yeah? 0:03:34.040 --> 0:03:36.400 We should have? We did, we did, they did, That's 0:03:36.400 --> 0:03:40.600 why we picked it. Yeah, but before we get into 0:03:40.640 --> 0:03:43.360 all of that, Aaron, what time is it? It's quarantin 0:03:43.360 --> 0:03:47.320 any time it is? And what are we drinking this week? 0:03:47.720 --> 0:03:51.920 Nothing other than little Blue pills? Yep, it makes sense. 0:03:52.040 --> 0:03:55.360 It makes sense. Pills, p I L s just one 0:03:55.480 --> 0:03:58.360 L just because because it's beer. It's a beer drink. 0:03:58.560 --> 0:04:04.080 It's a pill drink even and lemonade and blue curse out. 0:04:04.840 --> 0:04:08.120 Sorry sorry, but not that sorry, because it clever. 0:04:08.640 --> 0:04:10.880 I mean, we had to do the name and then 0:04:11.000 --> 0:04:14.800 the recipe was based on that, and so there you go. 0:04:15.080 --> 0:04:19.560 Enjoy it or don't. Yeah, anyways, you'll find the full 0:04:19.600 --> 0:04:23.320 recipe so you can decide for yourself for that quarantine 0:04:23.480 --> 0:04:26.560 and the non alcoholic. We'll do it plusy Brita on 0:04:26.640 --> 0:04:28.520 our website This podcast will kill You dot com and 0:04:28.680 --> 0:04:30.640 on all of our social media channels. 0:04:30.800 --> 0:04:34.400 And on our website you can find all sorts of goodies, 0:04:35.040 --> 0:04:39.400 including button not limited to transcripts, links to our bookshop 0:04:39.440 --> 0:04:43.360 dot org affiliate account, our goodreads lists, music by Bloodmobile, 0:04:43.839 --> 0:04:47.039 links to a first hand account, form, a contact us form, 0:04:47.400 --> 0:04:53.920 so many forms so show notes, Patreon, merch merar, repin' 0:04:54.080 --> 0:04:56.440 the shirt and our new shirt today which I just 0:04:56.520 --> 0:04:59.960 am still in love with so much so and other things. 0:05:00.320 --> 0:05:03.640 Check out our website. This podcast will kill you dot com. 0:05:04.000 --> 0:05:06.680 If you haven't already, please remember to rate, review, and 0:05:06.720 --> 0:05:09.840 subscribe on whatever podcaster you like to listen to so 0:05:09.880 --> 0:05:13.279 that you don't miss our new episodes, and because it 0:05:13.320 --> 0:05:15.440 helps us get up in the charts, which helps new 0:05:15.440 --> 0:05:19.080 listeners find our podcast. So thanks, we appreciate it. 0:05:20.640 --> 0:05:24.840 Aaron, can we get started? We can today's topic. 0:05:25.279 --> 0:05:26.880 Right after a short break. 0:05:50.200 --> 0:05:50.400 Still. 0:05:50.480 --> 0:05:53.920 Dentaphil is the medicine that we're talking about today, and 0:05:53.960 --> 0:05:57.960 it is of course most famous for its use as 0:05:58.000 --> 0:06:02.360 a treatment for erectile dysfunction under the trade name viagra, 0:06:03.320 --> 0:06:06.880 but that is not its only use, so I want 0:06:06.880 --> 0:06:09.840 to give credit up front that this is also an 0:06:09.839 --> 0:06:12.719 important medication that is used for the treatment of things 0:06:12.760 --> 0:06:18.000 like pulmonary hypertension in both adults but also tiny babies. 0:06:18.200 --> 0:06:21.520 Off label use, and that's a condition where the pressure 0:06:21.560 --> 0:06:23.839 in your blood vessels and your lungs is too high 0:06:23.880 --> 0:06:27.000 and it can make it really difficult to breathe. In babies, 0:06:27.040 --> 0:06:30.119 this is often because they're born premature. But I'm saying 0:06:30.120 --> 0:06:32.200 that now because that's mostly the last time I'm going 0:06:32.240 --> 0:06:36.360 to talk about it, because its use in other contexts 0:06:36.560 --> 0:06:40.839 is really overshadowed, of course by its fame as viagra. 0:06:41.960 --> 0:06:44.919 So to understand the use of this medication in the 0:06:44.960 --> 0:06:47.560 treatment of a rectile dysfunction, we have to start by 0:06:47.560 --> 0:06:51.520 talking about erections. What are they, how do they work, 0:06:51.920 --> 0:06:55.040 what is happening when they don't work, and why does 0:06:55.160 --> 0:06:56.119 viagra help? 0:06:56.800 --> 0:06:58.839 So we all love the questions that we should be 0:06:58.839 --> 0:06:59.920 asking exactly. 0:07:01.760 --> 0:07:06.279 There is the potential, as evidenced by multiple like twenty 0:07:06.320 --> 0:07:12.600 to fifty page papers on the detailed biochemical reactions and 0:07:12.760 --> 0:07:18.080 the neurobiology and endocrinology of what's happening in a penile erection. 0:07:18.560 --> 0:07:21.000 There's the potential to go into way too much detail, 0:07:22.440 --> 0:07:25.680 But for this episode I will link to all of 0:07:25.720 --> 0:07:27.920 those papers so people who want to dig deep can 0:07:28.720 --> 0:07:32.160 What we need to understand is really the broad strokes 0:07:32.560 --> 0:07:36.720 of what an erection is a penile erection is the 0:07:36.840 --> 0:07:42.760 end result of a pretty complex neurovascular process, which means 0:07:42.800 --> 0:07:47.560 that it involves a real web of our peripheral nerves 0:07:48.080 --> 0:07:51.120 as well as our brain and spinal cord. It involves 0:07:51.160 --> 0:07:57.120 both sensory and motor nerves, and both are sympathetic and parasympathetic, 0:07:57.240 --> 0:08:04.160 so those autonomic nervous systems. It coordinates through tactile, auditory, visual, 0:08:04.200 --> 0:08:09.160 and other stimuli, and involves a pretty wide range of 0:08:09.240 --> 0:08:13.280 neurotransmitters as well as hormones. And all of this has 0:08:13.320 --> 0:08:16.200 to coordinate with our vascular system, which is what deals 0:08:16.240 --> 0:08:19.840 with blood flow in and blood flow out. And we 0:08:19.880 --> 0:08:22.280 don't have to get deep deep into the details to 0:08:22.440 --> 0:08:27.400 understand how this works and how viagrass soldeniphil can affect 0:08:27.480 --> 0:08:30.800 this process, but we do need to understand the anatomy 0:08:31.040 --> 0:08:35.840 of a penis. So anatomically, the penis has some pretty 0:08:35.880 --> 0:08:40.760 specialized tissue creatively called a rectile tissue. Wow, okay, I know, 0:08:41.240 --> 0:08:44.520 such creative naming. So if you were to look at 0:08:44.559 --> 0:08:48.440 the interior of a penis, like in cross section, to me, 0:08:48.600 --> 0:08:51.240 it kind of looks like a fly with like an 0:08:51.240 --> 0:08:57.680 open mouth, going like ooh, okay, because like imagine a fly, 0:08:57.840 --> 0:09:00.079 a big fly eyes, but then they have like a 0:09:00.200 --> 0:09:01.800 human mouth going like, oh my. 0:09:01.760 --> 0:09:05.640 Gosh, I don't like that image, but continue, but it's 0:09:05.640 --> 0:09:06.480 in your brain now. 0:09:07.480 --> 0:09:10.480 So in cross section, it has these two big round 0:09:10.720 --> 0:09:14.120 almost really they're like tubes that are full of this 0:09:14.480 --> 0:09:20.280 spongy type of tissue that's called the corpora cavernosa. 0:09:20.320 --> 0:09:21.800 And each of these. 0:09:21.640 --> 0:09:26.360 Corpora cavernosa has an artery that flows through the center, 0:09:27.280 --> 0:09:32.360 and then these two sponges are surrounded by a pretty 0:09:32.520 --> 0:09:37.280 dense fibrous tissue that forms a sheath like a sword 0:09:37.360 --> 0:09:42.600 with a sheath. Right, it's a firm area, and that 0:09:42.760 --> 0:09:44.800 is what looks like the fly eyes, like this pair 0:09:44.840 --> 0:09:47.959 of big wide eyes. And then beneath that, like on 0:09:48.080 --> 0:09:50.920 the dorsal underside of that, if you're looking at a 0:09:50.920 --> 0:09:55.440 cross section, there's another tissue, spongy tissue tube called the 0:09:55.480 --> 0:10:00.440 corpus spongiosum, and inside this tube is the urethru where 0:10:00.520 --> 0:10:03.160 pa is going to come out as well as ejaculate 0:10:03.240 --> 0:10:05.120 is going to come out, and that's what looks like 0:10:05.200 --> 0:10:08.880 the mouth of the fly. This is surrounded by a thinner, 0:10:09.440 --> 0:10:13.920 fibrous sheath of tissue and then the whole thing is 0:10:13.960 --> 0:10:18.720 surrounded by a lot of different smooth muscle, not skeletal muscle, 0:10:19.040 --> 0:10:20.080 but smooth muscle. 0:10:20.679 --> 0:10:23.079 So just like a lot of different types of tissue 0:10:23.080 --> 0:10:24.400 all laggered together. 0:10:24.320 --> 0:10:27.120 A lot of different types of tissue in these three 0:10:27.520 --> 0:10:32.440 pockets of spongy area, okay, with a lot of smooth 0:10:32.520 --> 0:10:36.719 muscle tissue all up in there. And smooth muscle is 0:10:36.760 --> 0:10:39.200 the type of muscle that we have all of our bodies. 0:10:39.720 --> 0:10:43.440 It's what surrounds our arteries or is part of our arteries. 0:10:43.800 --> 0:10:46.480 It's what's in all of our internal organs, except for 0:10:46.520 --> 0:10:49.120 our heart, which has its own specialized kind of muscle. 0:10:50.280 --> 0:10:54.240 But unlike most other smooth muscle in our bodies, the 0:10:54.320 --> 0:10:58.800 smooth muscle that surrounds the corpora cavernosa in the penis 0:10:59.280 --> 0:11:03.880 is tonic contracted, which means that it's always a little 0:11:03.880 --> 0:11:07.080 bit though not one hundred percent completely, but it's a 0:11:07.120 --> 0:11:12.200 little bit clamped down contracted, rather than relaxed. And what 0:11:12.400 --> 0:11:16.959 that does is it allows for only enough blood flow 0:11:17.040 --> 0:11:21.360 through to keep the tissues of the penis healthy without 0:11:21.400 --> 0:11:26.160 allowing too much blood in. So what happens in an 0:11:26.160 --> 0:11:31.520 erection through again this complex series of neurotransmitters, hormones, blah 0:11:31.520 --> 0:11:36.559 blah blah. Is that this smooth muscle starts to relax 0:11:37.440 --> 0:11:41.840 and that causes the dilation of those arteries in the 0:11:41.840 --> 0:11:46.560 corpus cavernosa in those flies eyes, and that allows for 0:11:46.720 --> 0:11:51.360 increased blood flow. That blood flows out of the arteries 0:11:51.400 --> 0:11:55.000 into those tissues and fills up all of this spongy 0:11:55.120 --> 0:11:59.160 potential space. These are called sinusoids, and they're basically like 0:11:59.400 --> 0:12:04.840 chambers in those spongy tissues. And as those tissues begin 0:12:04.920 --> 0:12:10.360 to expand, they actually compress the veins in the penis, 0:12:10.400 --> 0:12:16.040 which are all located outside of that fascial tissue or 0:12:16.080 --> 0:12:19.120 in between layers of fashion, but outside of those sponges. 0:12:19.559 --> 0:12:22.320 So it's like let more blood in and prevent blood 0:12:22.320 --> 0:12:23.480 from leaving. 0:12:23.559 --> 0:12:28.080 Exactly exactly, and that traps the blood in those sinusoids 0:12:28.120 --> 0:12:32.520 in the sponge you have very little venus outflow. And 0:12:32.559 --> 0:12:35.560 the more that that process continues through this kind of 0:12:35.600 --> 0:12:40.840 positive feedback loop, then eventually you have a really significant 0:12:40.840 --> 0:12:45.240 increase in the pressure inside of the penis, and then 0:12:45.400 --> 0:12:49.800 you have a contraction of nearby muscles called the issio 0:12:49.920 --> 0:12:53.120 cavernosis muscles, and these are muscles like in the pelvic floor, 0:12:53.679 --> 0:12:57.160 not smooth muscles, but skeletal muscles, and that provides a 0:12:57.360 --> 0:13:00.280 further rigidity, so you have that's how you end up 0:13:00.360 --> 0:13:04.319 with the rigidity of an erection. Does that make sense? Yeah, 0:13:04.400 --> 0:13:06.520 that's it. That's all it is, right. I can make 0:13:06.559 --> 0:13:07.440 it as simple as. 0:13:07.280 --> 0:13:10.640 That more blood in, less blood out erection. 0:13:10.640 --> 0:13:14.440 Erection, and to do that you first need a relaxation 0:13:14.720 --> 0:13:19.000 of that smooth muscle. So then if we understand that, 0:13:19.160 --> 0:13:22.000 then we can understand that there's a lot of ways 0:13:22.000 --> 0:13:27.000 that this process could go wrong, and that end result 0:13:27.120 --> 0:13:30.040 is called a rectile dysfunction. And for this I'm going 0:13:30.120 --> 0:13:34.520 to just rely on nih definitions limited though they may be. 0:13:35.559 --> 0:13:39.120 A rectile dysfunction is the condition in which somebody cannot 0:13:39.200 --> 0:13:44.240 either achieve or maintain an erection that is firm enough 0:13:44.600 --> 0:13:51.120 for a satisfactory sexual experience. That's the literal definition. And 0:13:51.200 --> 0:13:56.920 there isn't one underlying cause of a rectile dysfunction. Erectile 0:13:57.000 --> 0:14:01.680 dysfunction is an end result, right, It's as satisfying sexual 0:14:01.720 --> 0:14:04.880 ability or the inability to have this satisfying sexual experience 0:14:04.960 --> 0:14:08.520 because the erection is not as firm as either it 0:14:08.600 --> 0:14:10.240 used to be or as you want it to be. 0:14:11.600 --> 0:14:14.760 Now again, there's limitations to this, and one thing that 0:14:14.800 --> 0:14:17.000 I'm not probably doing a good enough job in this 0:14:17.040 --> 0:14:20.440 whole episode is going into the nuances of how we 0:14:20.560 --> 0:14:24.560 define sexual health in general, right, or. 0:14:24.520 --> 0:14:27.800 What is the satisfactory sexual experience exactly? Right? 0:14:28.240 --> 0:14:30.840 Yeah, yeah, yeah, right, So like that is that is 0:14:30.880 --> 0:14:33.040 beyond the scope of this. But if we're sticking with 0:14:33.080 --> 0:14:36.280 this definition, then what we're looking at really is that 0:14:36.400 --> 0:14:42.080 erection itself. And there's a lot of different things that 0:14:42.120 --> 0:14:45.920 can end up causing a rectile dysfunction or a lot 0:14:45.920 --> 0:14:48.520 of different risk factors that end up relating to this. 0:14:48.920 --> 0:14:49.120 Right. 0:14:49.760 --> 0:14:53.120 There are of course psychosocial issues, like we said, like 0:14:53.280 --> 0:14:56.360 what is healthy sexual function? What does it mean to 0:14:56.480 --> 0:15:02.120 that individual? What's considered disorder? But you accept that I've 0:15:02.160 --> 0:15:04.600 got a disorder or I feel like there's a disorder. 0:15:04.960 --> 0:15:07.040 There's a lot of different things that can end up 0:15:07.040 --> 0:15:11.560 causing this. There's things like neurologic issues, whether that's a 0:15:11.600 --> 0:15:15.520 spinal cord injury or peripheral nerve damage or either like 0:15:15.640 --> 0:15:19.920 demielinating disease like MS or a whole host of other 0:15:20.040 --> 0:15:24.480 chronic diseases that can cause nerve issues. There's also endocrine 0:15:24.520 --> 0:15:30.200 issues like low levels of testosterone. There's also vascular issues, 0:15:30.400 --> 0:15:33.760 and vascular issues likely account for the majority of a 0:15:33.800 --> 0:15:37.120 rectile dysfunction, though it's a little hard to get great 0:15:37.200 --> 0:15:39.400 stats on this, but a lot of papers estimate like 0:15:39.480 --> 0:15:44.640 seventy percent or so. And vascular disease is not one thing, right, 0:15:44.640 --> 0:15:47.080 There's a whole bunch of risk factors that lead to 0:15:47.200 --> 0:15:50.440 vascular disease that can lead to a rectile dysfunction. Diabetes, 0:15:50.560 --> 0:15:53.640 high blood pressure, high cholesterol. All of these affect the 0:15:53.680 --> 0:15:55.760 lining of our blood vessels, which is going to affect 0:15:55.800 --> 0:15:59.680 blood flow, which is necessary for an erection. Aging in 0:15:59.720 --> 0:16:05.400 general causes oxidative stress and endothelial dysfunction, and then of 0:16:05.440 --> 0:16:08.200 course the hospital can do it to you, which it 0:16:08.280 --> 0:16:10.680 sounds like was what happened in our first hand account 0:16:10.720 --> 0:16:12.320 because someone had treatment for cancer. 0:16:12.320 --> 0:16:14.200 I was like, what do you mean. 0:16:15.840 --> 0:16:19.720 Treatment for something like prostate cancer or other operations or 0:16:19.760 --> 0:16:22.080 medications that can sometimes cause erect how dysfunction? 0:16:36.240 --> 0:16:39.960 Okay, Aaron, real quick, age? Why Like, I know you 0:16:40.040 --> 0:16:43.120 mentioned oxidative stress blah blah blah, but like, why what 0:16:43.560 --> 0:16:46.600 is the aging? Why does the aging process lead to 0:16:46.720 --> 0:16:49.800 higher rates of ED? Aaron This is. 0:16:50.160 --> 0:16:53.120 A question that made like I already was, I wondered this, 0:16:53.320 --> 0:16:58.600 but looking at the statistics, I wonder even more because okay, 0:16:59.040 --> 0:17:02.640 this is jumping ahead. But statistically people say that anywhere 0:17:02.640 --> 0:17:05.440 from like fifty to one hundred percent of people with 0:17:05.480 --> 0:17:10.080 a penis over age seventy have a rectile dysfunction. Okay, again, 0:17:10.280 --> 0:17:13.560 meaning that they're not having a satisfying sexual experience because 0:17:13.560 --> 0:17:16.040 they're not able to achieve or maintain an erection. 0:17:16.000 --> 0:17:18.919 Which real quick again, does that definition include frequency? Is 0:17:18.960 --> 0:17:21.520 that every time? Is that just once in a month? 0:17:21.640 --> 0:17:24.919 Is that once in a week? Like, it doesn't include 0:17:24.960 --> 0:17:28.520 any of that? It doesn't matter, right because it is subjective. 0:17:28.560 --> 0:17:31.200 It is it is a subjective experience that is meeting 0:17:31.240 --> 0:17:35.120 criteria for this dysfunction or disorder. Right, it's giving me 0:17:35.119 --> 0:17:36.080 menopause vibes. 0:17:36.880 --> 0:17:40.760 Where we're calling this a disorder because it is causing 0:17:40.840 --> 0:17:45.359 impact on your life, which is valid, But is it 0:17:45.440 --> 0:17:48.760 a disorder like evolutionarily? Maybe not? 0:17:49.080 --> 0:17:51.920 Right, I don't wait for it, just wait for it. 0:17:52.800 --> 0:17:55.120 There's more where that came from. We'll get you to it. 0:17:55.240 --> 0:17:59.199 I can imagine, because again it is very individual, like 0:17:59.280 --> 0:18:01.760 what is the satisy finding sexual experience for one person 0:18:01.840 --> 0:18:04.119 is not the same as for another person. For some people, 0:18:04.160 --> 0:18:06.600 it might not even include an erection, it might not 0:18:06.680 --> 0:18:11.159 even include orgasm. Like, there's so much nuance to this. 0:18:11.720 --> 0:18:18.080 What's the end goal here for Yeah, exact fixing, fixing, this, fixing, fixing. 0:18:17.880 --> 0:18:22.800 This, fixing, this and this in the case of erectile dysfunction, 0:18:23.000 --> 0:18:25.399 is just the firmness of the erection. 0:18:25.720 --> 0:18:30.240 But there is a real relationship between age and ED. 0:18:30.560 --> 0:18:34.199 So what is going on mechanistically? Like, what is the 0:18:34.200 --> 0:18:36.320 basis for this physiologically? 0:18:36.720 --> 0:18:39.960 Great question. I don't have a one single answer for you. 0:18:40.600 --> 0:18:44.359 I don't have like an aging equals this. There's a lot. 0:18:44.560 --> 0:18:47.040 There's the fact that as we age, all of those 0:18:47.080 --> 0:18:50.240 other risk factors go up. Cholesterol goes up, blood pressure 0:18:50.280 --> 0:18:53.879 goes up, the rates of diabetes go up. Aging also, 0:18:54.200 --> 0:18:57.320 like I said, already is thought to be independently associated 0:18:57.480 --> 0:19:01.119 with things that end up causing endothelial dysfunction, which is 0:19:01.480 --> 0:19:05.480 blood vessel dysfunction. Is it just that there's a lot 0:19:05.560 --> 0:19:08.560 of different factors. I don't think that there's one thing 0:19:09.240 --> 0:19:12.680 that aging causes that leads directly to a rectile dysfunction. 0:19:12.720 --> 0:19:14.560 I think it's a whole host of issues. 0:19:15.280 --> 0:19:17.400 I just have so many questions, but keep going. 0:19:19.800 --> 0:19:21.080 I don't know that I'm going to answer any of 0:19:21.080 --> 0:19:24.280 your questions. But out of all the different things, be 0:19:24.320 --> 0:19:30.720 they neurogenic, be they vascular, be they psychological, be they hormonal, 0:19:31.880 --> 0:19:35.880 Very often the first thing that is used for treatment 0:19:36.440 --> 0:19:40.240 is one thing, and that is viagra. So, no matter 0:19:40.280 --> 0:19:44.919 the cause, that's not usually investigated, first thing, often not 0:19:44.960 --> 0:19:49.800 even second thing, the treatment is a blanket viagra for 0:19:49.880 --> 0:19:50.560 all your woes. 0:19:50.880 --> 0:19:55.640 And so what percentage of cases of ED does viagra 0:19:55.800 --> 0:19:57.680 actually help with? 0:19:58.320 --> 0:20:01.200 Most papers I read estimated sixty to seventy percent. 0:20:01.480 --> 0:20:03.160 Wow, okay, it's pretty high. 0:20:03.280 --> 0:20:05.640 It's pretty high. Why is that? How does it work? 0:20:05.720 --> 0:20:11.240 Let me tell you, sildentiphyl viagra. It's a phosphodiesterase or 0:20:11.359 --> 0:20:15.919 PDE inhibitor. What does that mean. PDE is an enzyme. 0:20:16.000 --> 0:20:18.840 It's not one enzyme. It's a whole group of enzymes. 0:20:19.040 --> 0:20:21.840 And these enzymes are present on a whole bunch of 0:20:21.880 --> 0:20:25.719 our tissues throughout our bodies. But there's one in particular 0:20:26.000 --> 0:20:29.200 that viagra is very strongly like. It really only works 0:20:29.240 --> 0:20:34.080 on this one type of phosphodiastorse called PDE five and 0:20:34.320 --> 0:20:38.560 this particular phosphodiasterorate enzyme happens to be present in very 0:20:38.640 --> 0:20:42.800 high concentration in the corpus cavernosum of the penis. That's 0:20:42.800 --> 0:20:48.439 spongy tissue that's responsible for the majority really of an erection. 0:20:49.640 --> 0:20:54.640 So through this again very complicated series of biochemistry, the 0:20:54.760 --> 0:21:00.919 end result of blocking PDE five, which is what sildentiphil 0:21:01.080 --> 0:21:05.280 and other similar drugs do, It blocks the action of 0:21:05.320 --> 0:21:09.280 this enzyme and that results in this cascade of events 0:21:10.119 --> 0:21:16.239 that causes increased relaxation of that smooth muscle, So that 0:21:16.320 --> 0:21:20.120 allows for blood flow into the corpus cavernosum to start, 0:21:20.680 --> 0:21:23.679 and that allows the further steps of an erection to 0:21:23.680 --> 0:21:26.800 take place. That whole cascade of things can happen if 0:21:26.800 --> 0:21:29.960 you have relaxation of that smooth muscle and increased blood 0:21:29.960 --> 0:21:33.639 flow m H. And that's that's it. It can be 0:21:33.720 --> 0:21:34.480 as simple as that. 0:21:35.560 --> 0:21:38.119 What about other ed drugs. 0:21:38.359 --> 0:21:42.760 So Cialis is the trade name for tadalaphil, which you 0:21:42.800 --> 0:21:45.080 can tell by the A fill at the end that 0:21:45.160 --> 0:21:47.600 it's the same type of medication. It has like a 0:21:47.600 --> 0:21:50.359 different half life and blah blah blah, but it's still 0:21:50.440 --> 0:21:53.760 a PDE five inhibitor. So it acts in the same way. 0:21:53.880 --> 0:21:57.080 And there's a few other drugs that are really similar, 0:21:57.359 --> 0:22:01.160 just like different versions essentially but acting on the same 0:22:01.280 --> 0:22:04.800 end time. So all of those work in a very 0:22:04.840 --> 0:22:08.560 similar way. There are other medicines that are used. Some 0:22:08.680 --> 0:22:12.200 of them are like injectable medicines that you inject directly 0:22:12.200 --> 0:22:15.240 into the penis. Some of them are you can put 0:22:15.240 --> 0:22:18.239 them in other ways. A lot of them still like 0:22:18.359 --> 0:22:22.960 predominantly we target this phosphodiestors pathway. The other ones might 0:22:23.040 --> 0:22:27.600 target different PDEs, so PDE one instead of five or whatever, 0:22:28.000 --> 0:22:31.919 but that's predominantly what they're doing is targeting this pathway. 0:22:32.240 --> 0:22:34.760 Aaron, you said injectibles, and then you said and then 0:22:35.240 --> 0:22:37.680 put them in in other ways and you just try 0:22:37.720 --> 0:22:40.560 to skape right by that. Can you go back to that. 0:22:40.760 --> 0:22:43.000 It wasn't that exciting of other ways? I just mean 0:22:43.080 --> 0:22:47.760 like sublingual orkay, yeah, injectable. I don't think that there 0:22:47.760 --> 0:22:50.679 are any that are just topical though, I think that 0:22:50.680 --> 0:22:58.080 that's been tried. Yeah, Okay, not that exciting. So yeah, 0:22:58.119 --> 0:23:00.960 that I mean that that is honestly, that's the that's 0:23:01.000 --> 0:23:04.320 the basis of it. That's how viagra works, and that's 0:23:04.760 --> 0:23:14.280 why it works. Interestingly, sildeniphil still requires the initial steps 0:23:14.320 --> 0:23:18.280 of erection, which includes sexual arousal, so you still need 0:23:18.440 --> 0:23:21.160 first this neurologic input. 0:23:22.359 --> 0:23:23.879 Before you get. 0:23:23.680 --> 0:23:28.680 That relaxation of the smooth muscle from sildentophil, because it's 0:23:28.720 --> 0:23:31.080 not like direct. The way that it happens is like 0:23:31.240 --> 0:23:34.119 the build up of certain like precursors and then the 0:23:34.119 --> 0:23:37.879 blocking of calcium and blah blah blah. So sildenophil itself, 0:23:38.000 --> 0:23:41.560 viagra itself does not cause an erection. It also doesn't 0:23:41.600 --> 0:23:46.280 affect libido or sexual desire. All it does is allow 0:23:46.520 --> 0:23:50.679 for increased blood flow so that in the context of 0:23:50.720 --> 0:23:54.040 an erection it can be firmer and or lasts longer. 0:23:54.480 --> 0:23:57.760 Just opens the blood floodgates but waits for the signal 0:23:57.800 --> 0:23:58.840 from yeah. 0:23:58.920 --> 0:24:02.040 It like it makes the floodgates easier to open. It 0:24:02.359 --> 0:24:04.440 allows for there to just be like a gentle push 0:24:04.480 --> 0:24:07.160 instead of like a big shove like of a heavy door. 0:24:07.600 --> 0:24:11.760 Okay, So I have a bunch of questions. Okay, all right, 0:24:12.280 --> 0:24:14.000 you always see her on the commercials. If you have 0:24:14.040 --> 0:24:17.400 an erection lasting longer than four hours, et cetera, seek 0:24:17.520 --> 0:24:23.399 medical criapism. Right, Why is that happening. And second to 0:24:23.520 --> 0:24:25.679 that is kind of similar to that is like, what 0:24:25.720 --> 0:24:27.560 are some of the other side effects that we see 0:24:28.000 --> 0:24:31.400 with use of sildentophil and why do we see those things? 0:24:31.560 --> 0:24:34.440 Great question. So, of course any medicine has the risk 0:24:34.480 --> 0:24:37.840 of side effects. Most common side effects with viagara are 0:24:37.840 --> 0:24:41.760 things like headache or flushing. You can have some dizziness 0:24:42.200 --> 0:24:46.600 or like stomach upset, also, weirdly, nasal congestion. I don't 0:24:46.600 --> 0:24:49.879 actually know why that one happens. Most of these have 0:24:49.920 --> 0:24:52.040 to do with the fact that because this is acting 0:24:52.080 --> 0:24:55.600 on smooth muscle, and while it is specific to PDE 0:24:56.040 --> 0:24:59.880 five and that is mostly found in the penal tissues, 0:25:00.000 --> 0:25:02.879 it's also found in some other places. So this can 0:25:03.119 --> 0:25:06.919 cause relaxation of smooth muscle other places and then potentially 0:25:07.080 --> 0:25:09.760 drop your blood pressure and that might trigger some of 0:25:09.800 --> 0:25:14.840 these other symptoms. Really importantly, we see this happen if 0:25:14.920 --> 0:25:18.800 somebody is also taking a medicine that has nitrites in it, 0:25:18.920 --> 0:25:22.800 like nitroglycerin, which someone might take if they have angina, 0:25:22.960 --> 0:25:26.080 or like that pain in their chest that's from their 0:25:26.119 --> 0:25:30.399 heart having blockage. Basically, if viagra and a nitrite is 0:25:30.440 --> 0:25:34.280 taken together, these drugs actually interact with each other and 0:25:34.320 --> 0:25:38.199 then cause really severe drops in blood pressure, like potentially deadly, 0:25:38.640 --> 0:25:43.760 really problematic to take these two medicines together. Otherwise, viagra 0:25:43.880 --> 0:25:49.720 and similar medications are actually pretty safe most all the time. 0:25:50.160 --> 0:25:54.320 When priapism happens, so that like prolonged direction, that can 0:25:54.359 --> 0:25:58.639 be very dangerous because again with an erection, you're having 0:25:58.680 --> 0:26:01.720 a lot of blood flow through the arteries into the 0:26:01.760 --> 0:26:06.320 penis and very little blood outflow, so that pressure can 0:26:06.359 --> 0:26:09.600 really build up and end up. If it lasts for 0:26:09.680 --> 0:26:12.879