Unknown Speaker 00:00 Hi, welcome Speaker 1 00:07 to Rosalind Franklin University, College of Pharmacy top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Dr. Sean Kane 00:28 And now on to the show. Welcome to week seven, spring edition of Rosalind Franklin University's top 200 drugs podcast. I'm your co host, Dr. Kane. I'm Dr. Brotherton, and I'm Dr. Patel, and this week we're talking about men's health. So this is going to be benign prostatic hypertrophy, erectile dysfunction and bladder incontinence. So we'll go ahead and kick it off with our alpha one blockers. The first one is terazosin or Hytrin. So how does terazosin or Hytrin work? Speaker 3 00:57 Well, as far as the hypertension goes, it blocks the Alpha One receptors, and this leads to vasodilation of the vasculature, reducing the peripheral resistance and reducing the BP this way, as far as the BPH goes, there are alpha one receptors on the prostate, so this inhibition leads to a relaxation of the bladder neck tissues, and thus it minimizes the outlet obstruction. Dr. Sean Kane 01:26 So either way, we're hitting our alpha one receptor, blocking that receptor, and that causes smooth muscle to relax. So that's either in the vasculature, lowers your blood pressure, or on the prostate, where it allows for the urine to flow easier, where the prostate isn't squeezing down so hard. Is that right? Exactly? Speaker 4 01:44 Dr. Kane, what are some adverse effects that patients can expect from this drug? Dr. Sean Kane 01:49 So it's an anti hypertensive agent, so you'd expect things like dizziness, orthostasis. We can also see some somnolence or sedation with it, muscle weakness, peripheral edema, which is common with many of our vasodilators, and then also impotence. Now impotence sounds like a scary term, but we actually can see this with a number of our antihypertensives, and it's almost always reversible with Speaker 4 02:12 withdrawal of the agent. Yep, sometimes we over relax that smooth muscle. Things don't work the way they're supposed to. Now, on the flip side of that coin. I understand that there's a rare side effect called priapism. What is that? So? Dr. Sean Kane 02:26 Priapism is an erection that lasts for more than a couple hours. It's painful and it requires medical treatment, otherwise permanent damage can occur. Interesting. Speaker 4 02:35 Now, I understand that this is a blood pressure medicine, but I haven't seen very many patients on it. Dr. Patel, why isn't this a very popular medicine? Speaker 3 02:44 The medication is not very popular because it carries high risk when it's used in elderly patients, mainly because of orthostatic hypotension. So we want to avoid these agents in elderly patient for blood pressure control. Speaker 4 02:56 Now, you mentioned orthostatic hypotension. Is that a brand? Speaker 3 03:01 No, it is not a brand. It basically is a hypotension that is related with posture changes. So when elderly people try to get up from their bed, or there is a sudden change in their posture, it leads to drop in blood pressure. This can cause dizziness and imbalance in their gait, and they can fall. And as we all know, falls and elderly can be detrimental. Speaker 4 03:24 That does sound dangerous. Dr. Kane, I understand that when this is used for BPH, it's supposed to be taken at night. Yeah. Dr. Sean Kane 03:31 So the recommendation is to take the medication at night. And the thought being is that when you first take the medication, you're going to have a peak effect. So this is where the peak amount of orthostasis will occur. The thought is that maybe the patient can kind of sleep through that peak effect, and in the morning they'll have less orthostasis. Problem, though, is that a lot of these people are elderly and they have issues with urination, so it's common for these patients to need to get up at night to go to the bathroom. So not only are we giving them a medication that gives them orthostasis, but we're recommending that it be given at a time when maybe it wouldn't be best for them to be getting up quickly to use the restroom over the course of the night. Speaker 4 04:10 That does sound a little backwards. I understand you mentioned getting up quickly. Are there any things patients can do to decrease the likelihood that they'll experience orthostatic hypotension? Yeah. Dr. Sean Kane 04:20 So in patients, when they are lying or sitting and they want to start standing up, they should slowly do so and wait between lying down and sitting, and then wait from sitting to standing, maybe even brace themselves as they're getting up against a chair or a wall, in case they do get light headed. Speaker 4 04:39 Does that effect ever attenuate after a while of being on the medication. Absolutely. Dr. Sean Kane 04:43 So a lot of these medications, terazosin and doxazosin, we actually titrate up the medication over time, because the patient does develop some amount of tolerance to the orthostasis. Speaker 4 04:54 Interesting. I understand they can also drink more water to stay hydrated, to keep their blood pressure out. Up, which might help to avoid the side effect, but it might also make them have to get up to go to the bathroom more often as well. Dr. Sean Kane 05:05 Absolutely, by far the worst thing to happen is a dehydrated patient taking an alpha block group, because the orthostasis will be much more pronounced than a euvolemic or even a hypervolemic patient. Speaker 4 05:17 Very interesting. So now let's move on to the second agent in the class, which is doxazosin or Cardura. Doxazosin sounds a lot like terazosin. Are they similar? Speaker 3 05:28 Yes, when it comes to the mechanism of action, both the medications work the same. However, when it comes to some pharmacokinetic parameters, such as half life, doxazosin has a little longer half life, so 24 hours, versus 12 hours with terazosin but interestingly enough, both these medications are taken once daily Speaker 4 05:49 now, Cardura, that sounds like a cardiac medicine. Is this often used for hypertension? Dr. Kane, Dr. Sean Kane 05:55 so really, both terazosin and doxazosin, although they have FDA approval for hypertension, we don't use them strictly for hypertension. If we have a patient who has BPH and also has hypertension, it could be an okay agent to pick really. The reason is that doxazosin was in a trial called the ALLHAT trial, which was looking at hypertensive patients and comparing a number of different therapies. What they found was in patients who received doxazosin for their hypertension, there was actually an increased association of heart failure in that arm of the trial, and it was actually discontinued early because of that. We don't use it strictly for hypertension, but we may use it as a BPH medication with a side effect of reducing blood pressure. Speaker 4 06:38 Interesting. I understand doxazosin or Cardura is available as immediate release and XL tablets. How often do you take the immediate release tablets daily, and how often do you take the XL tablets daily? Ooh, what an improvement. Speaker 3 06:52 The third medication on the list is tamsulosin. The brand name is Flomax. And this medication is also an alpha one antagonist, but because it is a little bit more selective for the type 1A receptors, which are prevalent in prostate it mainly is used for BPH. Dr. Sean Kane 07:12 Now, one cool thing about the fact that it's more selective to the prostate tissue is that we don't have to titrate this medication like we do with the other two alpha blockers, so we don't see as much orthostasis with this. So we can kind of start the patient at their goal dose, as opposed to working them up over a period of days to weeks. Speaker 4 07:29 That is nice. So you're saying tamsulosin never causes orthostasis, right? Speaker 3 07:34 No, that is not correct. Dr. rutherton, it does cause its orthostasis. Speaker 4 07:38 That's correct, with the potential advantage of not having to titrate the medicine. This agent does cause orthostasis as well. So when doctors want to use this very expensive agent, you may be able to remind them that there are generic drugs with about the same side effect profile. Dr. Sean Kane 07:54 It's important to note that this is not FDA approved for hypertension, unlike terazosin or Hytrin and doxazosin or Cardura, although we would never use any of these medications for hypertension in the absence of BPH. Speaker 4 08:07 It's also interesting to note that sometimes doctors will prescribe this medication for kidney stones to help patients pass kidney stones, which is not an FDA approved labeling. Now, the brand name of this drug is flow Max. What do they mean by that Unknown Speaker 08:20 maximum flow? Speaker 4 08:21 Wow, that's a pretty good name for a BPH drug. When those patients have trouble stopping and starting their urinary flow. That's great. And I understand this comes as a capsule. Is it okay to open the capsule or break it or split it? Speaker 3 08:34 No, it is available as a point four milligram capsule, and the manufacturer recommends that the capsule should not be open, broken, obviously, or split. Dr. Sean Kane 08:42 So our next medication is finasteride, and we have two different brand names, one is Proscar and the other is Propecia. What's the difference? So Proscar is indicated by the FDA for BPH, whereas Propecia is about a fifth of the dose and it's indicated for hair loss. Speaker 3 08:59 Oh, ding, ding, ding. Dr. Brotherton, Speaker 4 09:03 so hair loss and BPH. What do these two diseases have in common, and how does this drug work Speaker 3 09:08 to treat them? Well, finasteride, basically, is a five alpha reductase inhibitor, and what it does is it inhibits the five alpha reductase enzyme which is responsible for converting the testosterone into something called DHT dihydrotestosterone. The Dihydrotestosterone is responsible for prostate tissue development and hair loss. So if you stop the DHT, you're stopping the hair loss as well as the increase in prostate tissue and thus it reduces the BPH symptoms. Very interesting. Dr. Sean Kane 09:42 It's important to note that this is for male pattern baldness in men. It's not an approved medication for women. And why is that they think that the pathophysiology of female pattern baldness is not related to DHT, whereas in men it is. Speaker 3 09:57 And the other reason it is not approved or recommended to be used in female patient is because this medication is pregnancy category X, so it is contraindicated in pregnancy as well as nursing mother. The active ingredient can be absorbed through the skin, so the female pharmacist or technician, if they're counting the pills on the tray, make sure they're wearing the gloves while handling and while, if the female is trying with the partner to conceive a child, they shouldn't handle the product as well, because it can negatively impact the fetal development. Speaker 4 10:33 Very interesting. And since this drug blocks sort of testosterone effects, I think it's cool that the adverse effects sort of follow with that, and we see the same sort of adverse effects as we can see in patients with low levels of testosterone, including impotence, a decrease in libido, an enlargement in the male breast, or breast tenderness and problems ejaculating as well. Dr. Sean Kane 10:55 So I think there's a couple important counseling points that are worthy of discussion. Probably the most important is how long it takes for the product to start working. So in patients who are taking Propecia for hair loss, it takes about three months for them to see any effect at all. And in patients who are taking Proscar for BPH, it can take six months or even longer to see any improvement in symptoms. Speaker 4 11:16 Wow, that's a long time. Is there any way to help patients have symptomatic improvement while they're waiting for this drug to take effect. Absolutely. Dr. Sean Kane 11:24 So the alternative is to use one of our alpha blockers, like terazosin or Hytrin and doxazosin or Cardura or tamsulosin or Flomax, because they work within a week or two, as opposed to six months. So moving on from agents that cause erectile dysfunction to agents that treat erectile dysfunction, we have three phosphodiesterase five inhibitors now, Dr. Patel, how do these agents work? Speaker 3 11:47 The PDE five inhibitors basically inhibits the PDE five, which is responsible for degrading the cyclic GMP. So because we are inhibiting the PDE five, there is prolonged effect of the cyclic GMP, and this cyclic GMP is responsible for relaxing the smooth muscle and increasing the blood flow. So erection works by increasing the endogenous nitric oxide levels, which this drug would eventually do. And also in lungs, these enzymes are responsible for relaxation of pulmonary Speaker 4 12:21 vasculature, so it probably has some utility then in pulmonary artery hypertension, right? Speaker 3 12:26 That is correct. So the brand names are different when it's used for erectile dysfunction versus when it's used for pulmonary hypertension, but those are the two FDA approved indications. Speaker 4 12:38 Now, Dr. Kane, Dr. Patel mentioned some nitric oxide being released. Do these drugs have any important drug interactions? Dr. Sean Kane 12:46 Absolutely so in patients who take nitrates for chest pain. So this would be nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or any other nitrate, they risk having a precipitous drop in their blood pressure if they take both agents together, Speaker 4 13:03 so too much nitric oxide really opens up the blood vessels and can cause a blood pressure drop, right? Absolutely. Now, I don't know a sensitive way to word this, but I have to ask if this is used in a male patient with pulmonary artery hypertension, is it possible that he'll suffer from unwanted erections, Dr. Sean Kane 13:22 absolutely not. So the way that these work is that we have to have that initial nitric oxide release, which is caused by some form of sexual stimulation. So you have to have that initial effect in order to generate cyclic GMP in order to inhibit the breakdown of it with phosphodiesterase inhibitors. So we have to have that first step in order for the erection to occur and continue to prolong. Speaker 4 13:45 Now, as with any drug that decreases blood pressure, I know that we see some some side effects related to that, such as headache, flushing and low blood pressure. What other sort of side effects do we see with these meds as a class? Speaker 3 13:57 So just like it was mentioned for terazathan, one of the rare side effects could be priapism, so unwanted or prolonged direction. There are some other visual disturbances that cannot happen as well, and there will be impairment in color discrimination, blurred vision or sensitivity to light. I've also heard patients seeing blue vision, especially with Viagra. So the Viagra, easy way to remember is, Viagra is a blue color pill, and your vision turns blue, and that's one of the side effect. And very rarely, this visual impairment can lead to vision loss. And another very rare side effect is hearing loss as well. Speaker 4 14:41 Now, speaking of Viagra, which goes by the generic name sildenafil, if this agent causes a drop in blood pressure that makes the patient pass out, is that called Viagra falls. No. Speaker 3 14:52 Dr. Brotherton, I don't know about Viagra falls, but I do know the brand name is named after Niagara Falls, and that is a true story. Speaker 4 15:00 So I've heard that Viagra, the blue pill, does cause this blue vision change that you talked about Dr. Patel, and I've also heard that that's because it inhibits phosphodiesterase six in the eyes more so than some of the other agents in this class, and results in that blue vision change. That is correct. So I Dr. Sean Kane 15:18 think one interesting thing to talk about is that we have two different products. We have our erectile dysfunction product, which goes under the brand name of Viagra. Then we have our pulmonary hypertension product that goes under the brand name of Revatio. So our next agent is vardenafil, the brand name is Levitra. And unlike our other two PDE five inhibitors, this does not have an FDA approved indication for pulmonary hypertension. Speaker 4 15:43 I also understand that this one doesn't really cause the blue vision, so it might be a good option for patients who are bothered by that when taking Viagra. Speaker 3 15:50 And interestingly enough, this medication is not only available in regular tablet, but also in ODT form, and it contains peppermint flavor, yummy. Dr. Sean Kane 16:02 So similarly to sildenafil or Viagra, the onset of action of Levitra is about one hour, and it lasted a little bit longer, between three and six hours. Speaker 4 16:11 Now I also understand that there's a third agent in this class called tadalafil or Cialis. Unknown Speaker 16:16 That's the last contender. Dr. Sean Kane 16:18 So in pharmacy school, I learned that kind of the street name, if you will, for tadalafil or Cialis was the Weekender. The reason is that, unlike sildenafil, Viagra or vardenafil, Levitra, tadalafil lasts a full 36 hours with one single dose. Speaker 4 16:35 So you can take it well before the time that you're due to Cialis. Dr. Sean Kane 16:40 So the other interesting thing about Cialis or tadalafil, in addition to the fact that it lasts so much longer, is that it's FDA approved to be given as a once daily formulation where you don't have to plan your dose around your sexual schedule. Speaker 4 16:53 That does sound handy, although I will say that most insurances won't cover it. Speaker 3 16:58 And I also heard that the medication is recently approved for the treatment of BPH. Is that correct? Dr. Kane, yeah, Dr. Sean Kane 17:05 so it's approved for BPH for erectile dysfunction and for patients who have both BPH and erectile dysfunction. Unknown Speaker 17:13 Interesting, killing two birds with one stone. Speaker 4 17:16 And I also understand that in addition to those two indications, under the brand name Adcirca, tadalafil is approved for pulmonary hypertension, but it's got a much nicer dosing schedule than Revatio does, and it's 40 milligrams once a day. Dr. Sean Kane 17:29 So kind of changing gears here. Our next two agents are going to be medications that are used for neurogenic bladder or urinary incontinence. The first one is called oxybutynin, and the brand name is Ditropan. Speaker 3 17:44 So like Dr. Kane said, This medication is used to treat the symptoms related to neurogenic bladder. The symptoms can be urgency, frequency, leakage or urge incontinence. Dr. Sean Kane 17:57 The way it works is essentially it's an anticholinergic agent so it calms the urinary bladder and it helps alleviate some of the overactive bladder symptoms. And it does this by relaxing some of the smooth muscle of the bladder that allows the bladder to be filled more, and it also decreases some of the contractions of the bladder, which can sometimes signal the patient to feel like they need to urinate. Speaker 4 18:21 Now that sounds like a handy use of an anticholinergic medicine, but I understand that medicines in this class generally have very similar side effects. What sort of things can patients expect when they're taking an anticholinergic like oxybutynin or Ditropan? Speaker 3 18:34 So think about all the anticholinergic side effects that we have discussed in previous recordings, such as headache, dizziness, blurred vision, dry eyes, xerostomia, which is dry mouth, constipation, nausea, or somnolence. Unknown Speaker 18:50 Dr. Kane, what kind of dosage forms is this available? Dr. Sean Kane 18:52 It's kind of interesting. We have a number. The main one that most of our listeners are going to see are Ditropan tablets, which are immediate release, or Ditropan XL, which is extended release. We also have Ditropan syrup. We have a topical gel called Gelnique. Then finally, we have a newer product called Oxytrol, which is a transdermal patch that you apply twice a week. And this is actually now available as an over the counter product, is there anybody Speaker 4 19:21 who shouldn't use Oxytrol, Ditropan or oxybutynin? Dr. Sean Kane 19:26 So just like many of our other Anticholinergics, because of the way it works, we should avoid it, or even consider it contraindicated in patients who have uncontrolled narrow angle glaucoma, gastric or urinary retention, because it's going to make those problems worse. Speaker 4 19:40 And I understand there's another agent in the class, which is the next drug on our list, tolterodine or Detrol. This is used for the same things, has the same side effects and ADRs and almost the same contraindications. Speaker 3 19:53 Is that right? That is very correct. Dr. Brotherton, Dr. Sean Kane 19:56 birds of a feather flocking together. So really, there's not much to say about Detrol, aside from the fact that we have Detrol and Detrol LA, which is the extended release version of the product. So moving on to our two over the counter products. The first is called minoxidil. The brand name is Rogaine. Speaker 4 20:13 Now minoxidil, I see the beginning of the word dilate in there, and I understand that this drug was actually invented as drug to treat high blood pressure by opening up the blood vessels or dilating them, and they decided to repurpose it as a hair growth treatment when they realized that their patients were growing some hair Dr. Sean Kane 20:33 absolutely and one of the reasons that we don't commonly use this as an antihypertensive is it has a number of very unique but very severe adverse effects associated with it. The interesting Speaker 3 20:44 thing about this over the counter hair growth product is that it's approved to be used in both men and women versus, remember, we talked about Propecia, it's only approved in men. Yeah, women can't even touch that one, right? That is correct. So how do I, I mean, how does the patient use this drug. Dr. Sean Kane 21:01 So there's two different types of dosage forms that are available. We have for men, a 5% foam or a topical solution that contains 30% ethanol. For women, we have a 2% solution that contains 60% ethanol. Speaker 4 21:15 That's a lot of alcohol. I imagine that could be irritating if it was applied to broken or open skin, right? Speaker 3 21:21 That is correct, and that's one of the side effects of this product, is some pruritus or local irritation. Speaker 4 21:28 And so how does this magical medication make people regrow their hair? Dr. Sean Kane 21:32 So we don't know exactly how it works for hair growth. The proposed mechanism is that it increases blood flow to the cutaneous tissue in the scalp, which allows more blood flow to get to the root of the hair and allows it to grow. But we really aren't all that sure exactly how it works. So our last agent is kind of different from many of the other agents that we've talked about. This is called nonoxynol-9, and it doesn't really have a brand name because it's used in a number of different products, all of which are used for Speaker 3 22:53 contraception. So what is nonoxynol-9? Speaker 4 22:07 I understand that it's a non ionic detergent that kills sperm. So when you don't want to have kids, you say, no, no oxen all no nine. It's got no in it many times. So that's how you can remember that it's for people who want no children. Dr. Sean Kane 22:23 The problem, though, is that in people who use this for mono therapy, where they don't use a condom or oral contraception, the failure rate is quite high. So anywhere from 15 to 30% of people in a one year period will have therapeutic failure of this contraceptive agent. Speaker 4 22:39 Now that's not very effective. Now, this is a detergent of some kind, so I imagine it kills and protects against all sorts of STDs as well, right? Speaker 3 22:48 I was wondering about that too, because I saw that verbiage. What do you have Dr. Sean Kane 22:51 to say? Dr. Kane, when nonoxynol-9 first came out, they actually thought that it would be effective in patients to prevent STDs, because it could kill things like gonorrhea, chlamydia, syphilis, maybe even HIV. The problem, though, was when they studied it in this way, it didn't protect at all. And actually, the patients who use this as their monotherapy form of contraception actually had higher rates of STDs. Speaker 4 23:16 That's interesting. So as a pharmacist, if you see someone in your family planning section looking like they're going to just try to use nonoxynol-9 without anything else. Maybe you should counsel them otherwise, because it's not effective at preventing STDs and it's not great at preventing pregnancy either, and Speaker 3 23:31 not to mention the detergent properties, can also cause some irritation to the mucosa. Unknown Speaker 23:36 So how is nonoxynol-9 supplied? Dr. Sean Kane 23:39 So for the most part, people in retail pharmacies may see nonoxynol-9 as an adjunct agent that comes with certain types of condoms where nonoxynol-9 is built into the condom itself. There are other dosage forms, though. So as we mentioned, it comes as creams, jellies, foams, gels, things that you would use as mono therapy. We also have something called the today sponge, which actually has two different mechanisms. So it does contain nonoxynol-9, which is our spermicide, but it also has a mechanical barrier that prevents sperm from entering the cervix and causing fertilization. So we've covered a lot of ground today. The first agent we discussed was terazosin or Hytrin. Then we Unknown Speaker 24:19 talked about doxazosin or Cardura. Speaker 3 24:22 The third agent was tamsulosin Flomax. Then we Dr. Sean Kane 24:25 moved on to finasteride, with two different brand names, Proscar, which was for the prostate and Propecia, which was for hair growth. Speaker 4 24:32 The next agent we talked about was the first PDE five inhibitor, the little blue pill that causes blue vision changes, sildenafil, or Viagra. Speaker 3 24:41 The next agent was vardenafil or Levitra. Dr. Sean Kane 24:44 And then we finished off the PDE five category with the Weekender, which was tadalafil or Cialis. Speaker 4 24:51 The next agent that we talked about for overactive bladder is oxybutynin or Ditropan. Speaker 3 24:56 And then we talked about the cousin of oxybutynin, tolterodine or Detrol. Dr. Sean Kane 25:01 And then we went to the over the counter section and discussed minoxidil or Rogaine. Speaker 4 25:06 And finally, we finished with nonoxynol-9. Dr. Sean Kane 25:10 Well, that concludes week seven, spring edition of Rosalind Franklin University's top 200 drugs podcast. I would like to encourage our audience to give us a five star rating in the iTunes store so that other pharmacy students outside of Rosalind Franklin might be able to find us a little bit easier. And with that, I'm your co host, Dr. Kane. Unknown Speaker 25:27 I'm Dr. Brotherton And I'm Dr Unknown Speaker 25:28 Patel. Study hard. Speaker 1 25:33 This has been an educational production by the Rosalind Franklin University, College of Pharmacy. Dr. Sean Kane 25:37 This podcast is copyright Rosalind Franklin University of Medicine and Science, Speaker 1 25:42 no participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a health care provider. Theme music for this podcast is an excerpt of Metro mass by sea salt, released under Creative Commons. You.