Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 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. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk, Episode 65 I'm your co host, Dr. Kane. I'm Dr. Sherman, and I'm Dr. Mattel. And today's episode is entitled advanced hypertension ninja skills with some of the oldest blood pressure medications. Today, we'll be focusing on three blood pressure medications that are still used in clinical practice, but are definitely not first line and really what clinicians need to know about these three medications in terms of why they're not on the radar in terms of first line therapies, and then also what to know about them, particularly in terms of the side effect profile of those medications. Speaker 1 01:04 So we're going to talk about clonidine, methyldopa, and minoxidil at great length. And I Dr. Sean Kane 01:09 think it's important to kind of step back for a second and think about who decides what is the first line anti hypertensive, and what criteria do they use? And if we go back literally two decades, we're looking at 1997 this is when JNC six came out. We're all the way up to JNC 8 right now. But what did JNC 6 tell us about preferred anti hypertensives at that time? Speaker 2 01:30 So what they said is, for uncomplicated hypertension, first line therapy there is going to be beta blockers, or thiazide diuretics. Yeah. So yeah, that's again, that's a great point. So that's something now that really is with these later guidelines, as we'll see, has fallen out of favor for the management of pure hypertension, although obviously for various other cardiologic abnormalities, arrhythmias, for example, there's still plenty of justification for them. Speaker 1 01:53 And then JNC seven, that was published in 2004 said that first line therapy for uncomplicated hypertension would be thiazide diuretics. Dr. Sean Kane 02:03 And then at that point in 2014 we had JNC eight, which we covered in episode two of HelixTalk. It basically said that if you're a non African American patient, you can pick from four potential drug classes for uncomplicated hypertension, thiazides, ACE inhibitors, ARBs and calcium channel blockers. And if you're African American, you may not have as robust of a blood pressure response to the aces and ARBs. So in that patient population, potentially consider a thiazide or calcium channel blocker as a first line therapy. Speaker 1 02:34 If you want to learn more about J and c8 guidelines in detail, please listen to our helix episode number two, Speaker 2 02:41 so again, there's a lot of these other antihypertensives that are not first learned, are still being used. And so again, one of them already mentioned was beta blockers, other things like hydralazine. And there's a lot of these clinical scenarios, of which you may say, oh shoot, we need to use one of these other ones. So maybe the most common two scenarios would be the first one pregnancy. So again, there probably don't want to use an ACE inhibitor or an ARB thiazide, generally not recommended, and then treat and resistant hypertension. So despite multiple agents, again, for those pharmacy students or anyone's other after, of course, assessing for compliance with the medication, things like that, but if you're still unable to meet the goal, what do Dr. Sean Kane 03:14 you do there? And so again, in today's episode, we're really focusing on three with the acknowledgement there's plenty of kind of lower tier antihypertensive agents out there, but the three we're going to focus on are clonidine, methyldopa and minoxidil. And really the reason that these aren't first-line therapies in all three cases is that we lack high-quality comparative clinical outcomes data. Speaker 1 03:40 So you're trying to say that we can reduce the surrogate marker, which is the blood pressure, with these medications, but the actual clinical endpoint, which is to reduce those cardiovascular morbidity and mortality type things like stroke, heart attack. We haven't seen that with these reagents. Speaker 2 03:56 Yeah, kind of like is the same thing we've gone through with statin medications or these other medications for cholesterol: we lower your cholesterol, and then what's the same thing here is in the and then what is been, what's inhibiting a lot of these other medications? Dr. Sean Kane 04:09 For a long time, we just thought that lowering the blood pressure itself, the number was good enough, just like what we thought with lipids. And then when ALLHAT came around, which was a very large comparative clinical outcomes trial, they actually had an alpha blocker in the trial called doxazosin. And in that trial, they actually removed doxazosin as an arm early, because they saw a signal of higher incidence of heart failure with doxazosin versus chlorthalidone (the thiazide) in that trial. And that really prompted the discussion of, maybe it's not enough to just change your blood pressure number, but we do need these comparative clinical outcomes data to support whether a given anti hypertensive should be a first line or not a first line. Speaker 2 04:52 All right, so let's get into the first one of these agents. So first one's clonidine. This one's FDA approved, like all these. These are, you know, oldies. So first approved. Back in 1974 and again, despite its age, it's not first line because, again, lack of comparative data. Speaker 1 05:08 So the way clonidine works is that it stimulates presynaptic alpha-2 receptors. Essentially, it's a negative feedback. So by stimulating this receptor, it will decrease the output of norepinephrine from the neurons. Speaker 2 05:23 Yeah, the way I explain it to my students is that what happens is when you release enough norepinephrine into the synapse, some of it then moves and goes presynaptically as well. And as it goes presynaptically, it hits some of these presynaptic autoreceptors, and then again, that shuts down the release downstream. So it's a beautiful way of having a check and a balance system if you're overloaded with one neurotransmitter. You get less of it, so you kind of balance things out. Dr. Sean Kane 05:45 So really, clonidine is tricking that neuron to release less norepinephrine by pretending that there's too much norepinephrine in the synapse. One thing to know about clonidine, at least in the ICU, this is one of my favorite antihypertensives to use because it's very quick onset, very quick offset. It's easy to titrate, but also I love using it in patients who have hypertension secondary to withdrawal syndrome. So alcohol withdrawal, opiate withdrawal as an example, it does a great job of blunting some of the sympathetic tone that goes along with those withdrawal syndromes. Yep. Speaker 2 06:18 And the more we spend in our substance abuse treatment program, the more we've been using this, or for those individuals that come in, and for a number of reasons, whether it's anxiety, whether it's not among other meds, but a lot of times it is because of acute withdrawal. And again, we get couple doses of this, till we get them back in our program and really modifying some of the long term regimens. And so then another interesting off oil abuse of it can be for things like Tourette Syndrome. One thing we know about this again, is by working with norepinephrine, again, providing that outer receptor, again, kind of calming down the system overall. So something like Tourette's Syndrome, as well as on a related note, if somebody has ADHD, this can be an off label medication used especially somebody has Tourette's or a tick disorder, all which are modulated by dopamine. And so we don't want to increase dopamine in these situations. In these situations. So another way of getting a similar response would be to actually, somewhat counterintuitively, is to hit the autoreceptors for norepinephrine. Speaker 1 07:10 So gearing back to hypertension treatment, there are about a couple different dosage forms available. You can use either oral tablets or transdermal patches. The oral tablets are available in 0.1, 0.2, or 0.3 milligrams. They're usually taken twice a day; higher doses are very rarely used. The transdermal formulation is also available in 0.1, 0.2, or 0.3 milligrams per day, and the patch is applied once weekly. Dr. Sean Kane 07:38 What's interesting about clonidine, because it's such an old drug, we actually see this pattern in older drugs, is that we acknowledge that it is renally eliminated, the half life dramatically increases with renal impairment. But despite that, because it's an older drug, and because of how the FDA regulated drugs at the time, we don't have a lot of guidance in terms of dosing adjustments if you do have renal impairment. So all we can kind of say is that, if you're a dialysis patient, your half life will be longer. You definitely don't need tid dosing, maybe not even bid dosing, you're going to be a lot more sensitive to it, because you're going to accumulate more the drug. But in terms of Max doses or max frequencies, anything like that, we don't have great data to kind of support specific dosing recommendations. Speaker 2 08:20 Yeah, we've got one gentleman right now, for example, whose estimated creatinine clearance is around 10 mL/min. He's on the clonidine patch. But again, we have continued to monitor him, and so far haven't seen any indication of accumulation leading to hypotension. But again, a great point about continuing to monitor that periodically, and Dr. Sean Kane 08:37 just to touch on the patch dosage forms, it's kind of interesting, how relatively low the patch doses are. You know, these are about 0.1 to 0.3 mg/day. We already talked about a typical oral dose being 0.1 mg BID, maybe 0.2 mg BID. So the patch dose is relatively low compared with typical oral dosing. So we have to keep that in mind when considering a clonidine patch — a patient may need two patches if they're on a high oral clonidine dose, because the patch strengths are limited. Speaker 1 09:10 So we talked about renal impairment and potential for drug accumulation leading to hypotension. But what are some of the other side effects that we see with too much drug? Speaker 2 09:20 so again, I think one of them is that it has a sedating profile. Again, some of the effects on stopping norepinephrine, and that's where it's used for some of that agitation. Use it to its advantage, agitation in somebody who is on acute opioid withdrawal, but on the same time, if somebody doesn't want to be sedated, that can be a concern. And I believe Dr. ain, there's similar medications you see routinely in practice that also work on a similar mechanism that are used for Dr. Sean Kane 09:42 that reason. Yeah. So there's an ICU sedative called dexmedetomidine (Precedex) that has essentially an identical mechanism. So it's a presynaptic alpha-2 agonist. So it does the same thing. Maybe it accumulates in the brain tissues differently, or hits receptors slightly differently, but essentially it's the same thing. We use it as a sedative. In the ICU, it's not as effective for sedation as, let's say, a benzodiazepine, but we still use it. So it's not surprising that a similar mechanism, drug like clonidine, will also cause some amount of sedation. In terms of other side effects that we see, we see dry mouth with this sometimes, if you're a renal transplant patient and you want the patient to intake more fluids in order to hydrate them. Sometimes this is an agent that's used to take advantage of that side effect to, you know, help the patient take in more fluids, like with many other antihypertensives, we do have a side effect of impotence with this medication. But again, that's fairly common with many antihypertensive medications, and because we're blocking norepinephrine, especially, we aren't stimulating the SA and the AV node like we would normally with our sympathetic tone. So we do potentially see bradycardias And maybe something like a first degree AV block, just because we're kind of blunting that sympathetic tone that may be necessary for a patient to have, you know, a normal heart rate or heart rhythm. Speaker 1 11:02 So these are very important side effects. But I think the biggest point where a pharmacist can come and play is educating patient, as well as other healthcare providers, please, if the patient's been on it chronically, do not stop it abruptly, because there are great withdrawal side effects. Speaker 2 11:18 And again, this is a pet peeve of one we look for in an acute psychiatric setting as well. As you know, we consistently just keep this on for a long term and bring somebody in, and let's say we're managing their with their withdrawals, and we say, well, we're just gonna continue them on a scheduled regimen, and we were gonna knock them out with hypotension. Or when they continue them on it, they go home, they're on it for a while, they eventually stop it. And we cause the withdrawal when really only you needed was two to three doses initially, when when somebody was was in that acute setting, and they have the acute withdrawal. So we'll be looking for again, rebound, hypertension, headaches, tremor, tachycardia, sweating. Again. From now, we have an outflowing of norepinephrine, and it's hitting all of its receptors and causing, again, all the effects of what norepinephrine does across the body. Speaker 1 11:58 So then we just talked about the difference in dosing between the oral meds versus the patch. Patch is a little bit lower dosing. Would you say those withdrawal symptoms happen less with the patch compared to the oral dosing, Dr. Sean Kane 12:09 for sure, and really the reason for that is that with almost any patch you use, you get a depot effect, which means that the drug kind of hangs out in the skin as you slowly absorb it, so it kind of has a self tapering effect to the patch. The patch takes about three days to kick in, and it also takes a couple days for it to go away completely because of that depot effect. So patients may still have some withdrawal, but definitely not nearly as bad as the oral formulation. And if you have a patient on a chronic clonidine patch, you may actually consider giving them some oral clonidine if you really anticipate a withdrawal syndrome from happening, but it should be way better than if they were just on the oral clonidine alone. Speaker 1 12:49 So what's the drawback, really, for using the patch, as with any patch? Speaker 2 12:52 Again, the one thing we do have to educate on is contact dermatitis applying to the appropriate sight, hairless, not inflamed, things like that. Dr. Sean Kane 13:00 And really, aside from cost, it's a little bit more costly than a typical oral regimen of clonidine. Another potential benefit of the clonidine patch is that you aren't getting this dramatic peak effect. So things like the sedation, the dry mouth should be better because you aren't getting this high peak effect that is probably causing some of those side effects. Speaker 1 13:19 So if I have a patient in the clinic, and I've used all the antihypertensives, and now I finally decided to put him on clonidine. And let's say the blood pressure is 169 over 103 can I give them patch, hoping that it will bring down the blood pressure right away? So again, Speaker 2 13:35 as I believe, as Dr. Kane's already mentioned, it's going to take a couple of days. So one thing you consider is a three day Pio to patch taper. We start them off on the oral and eventually then give them, once it starts kicking in, you kind of do almost a bridge, essentially. And once they're the patch kicks in, pull off the oral medication. Dr. Sean Kane 13:52 And then one final thing to think about with clonidine is a potential concern of using clonidine as systolic heart failure. This is super interesting, because, literally, clonidine has been out on the market for almost 50 years now we still don't know if it's safe to use in systolic heart failure. The reason why it might not be safe is that the sympathetic tone is important for things like inotropy and chronotropy, especially inotropy and those with systolic heart failure. With that said, we do use things like beta blockers that also have that effect, but are actually beneficial in heart failure. Really, the question mark comes because clonidine like drug called moxanidine, was studied in systolic heart failure, and it actually caused worse outcomes, worse mortality versus placebo. So on the basis of this clonidine like drug, there's a potential concern of using clonidine in systolic heart failure, but again, we really don't know that much about it, so at this point, it's definitely not a contraindication, but potentially might be a precaution to think about. All right, so I think Speaker 2 14:50 we're ready to move on to our second of these medications. So this one's again another oldie, maybe not a goodie. We'll see — methyldopa was FDA approved back in 1962. Again, due to lack of comparative data (especially outcome data), we don't really use this one as first line. In pharmacy school I was taught there's one key point about this medication — I'm pretty sure I either had it on the NPLEX or it was on a couple exams — and that is: it's considered a first-line option for hypertension in pregnancy. Dr. Sean Kane 15:19 And I'll absolutely second that — when you hear methyldopa, you think pregnancy, and that's basically baked into you since pharmacy school. With that said, though, maybe that's not the end all to be all for pregnancy hypertension, Speaker 1 15:33 so it was preferred per JNC 7 because of the long-term studies showing safer outcomes in pregnancy. But if we compare that to some of the other agents, like labetalol, those agents may be preferred over methyldopa because of a more favorable side-effect profile. Dr. Sean Kane 15:50 And really we have to distinguish safety to the fetus, safety to the mother, and then efficacy as well. For the most part, efficacy is similar between them. But there are side effects of methyldopa that labetalol or nifedipine XL, for example, don't carry; for that reason, methyldopa may no longer be the automatic choice in pregnancy as once taught. Speaker 1 16:16 and we always almost look at the JNC seven for recommendation on a hypertension treatment. But if you kind of look outside of it, NICE guidelines recommend using labetalol, methyldopa, or nifedipine XL for hypertension control in pregnancy. Speaker 2 16:32 And similarly, a 2014 Cochrane review (linked in our show notes) suggests that labetalol and nifedipine XL may be more effective and are at least as safe compared to methyldopa, although the data are not robust. Dr. Sean Kane 16:47 So I think it's safe to say for the most part, when you see methyldopa it's very likely the patient was pregnant or is pregnant — that's the niche where you'll most often see this drug. Speaker 1 17:03 and I think the pharmacist may be consulted when it comes to transitioning a patient on methyldopa, and then once the pregnancy is concluded, transitioning them back to the previous antihypertensive medication. So we can play a good role there. But the important question is, how does it work? Speaker 2 17:20 I think that's going to be that's a lengthy question. So essentially, one way to look at it is that it produces a it's a false neurotransmitter, so it becomes converted into something called alpha-methyl norepinephrine. So just like a lot of dopaminergic compounds become norepinephrine, this one becomes alpha-methyl norepinephrine, which replaces norepinephrine in neuronal vesicles. Once released, it probably acts similarly to clonidine — as an alpha-2 agonist reducing sympathetic tone. Dr. Sean Kane 17:48 so basically, it replaces your norepinephrine. And when the body thinks it's releasing norepinephrine, it actually releases the active metabolite of the drug, which happens to be a clonidine like drug, yeah. Speaker 2 18:00 And then there's also some other evidence talking about it maybe working on dopa decarboxylase, and so having a kind of similar effect to carbidopa using Parkinson's, and again, in that case preventing conversion as well, and so blunting some of that response to norepinephrine. Dr. Sean Kane 18:14 And for me, I think one of the really neat things about this drug is that it's basically stored in the body in these neuronal vesicles, which means that even once the drug leaves the blood, your body might still have some in these vesicles, and when it has this fight or flight response, is going to be releasing the active version of the drug. So this is a great example where the pharmacokinetic half life in terms of the half life in your serum may not correlate with the pharmacodynamic properties in terms of the anti hypertensive effect of the drug. So in terms of how it's available, it's available as tablets. You take 250 or 500 milligrams, typically twice a day or three times a day, although higher doses are sometimes used. And just like with clonidine, this is also renally eliminated, potentially have a longer half life in renal impairment. But specific dosing adjustments aren't really provided in the package insert. Speaker 1 19:02 So because it works like clonidine, the side-effect profile can be similar — sedation, dry mouth, and impotence are possible with methyldopa as well. Dr. Sean Kane 19:14 Absolutely, again, if you recall for the most part, this is a drug used in pregnancy, and I did an extensive PubMed search, and I wasn't able to find any case reports of impotence in pregnant females, but I'm still looking for more data on that. Speaker 2 19:31 So other things to monitor with that medication include salt and water retention (edema). Blood pressure effects may be best when given with a thiazide or loop diuretic to help remove some of that fluid. And then in pregnancy, you do have to keep in mind, though, that again, the whole reason we got to this point is because thiazides and loops probably need to be avoided. Dr. Sean Kane 19:52 So it's kind of a double edged sword, right? So it's causing salt and water retention. Typically, you do need a thiazide or loop to kind of deal with the side effect. Although that drug class (diuretics) is typically avoided in pregnancy, if a pregnant patient needs methyldopa they will probably have some degree of edema associated with the drug that may be harder to treat compared with a nonpregnant patient. Speaker 1 20:17 And you're telling me that pregnant females on methyldopa don't have any issues with fluid retention? Dr. Sean Kane 20:22 right? I'm going to avoid that question. Speaker 1 20:25 So talking about the common side effect, we can also focus on some of the uncommon side effect, but they're rare, but they could be detrimental. And those could be hepatotoxicity. They couldn't be usually transient and mild. In rare cases, it could be serious. The other one is autoimmune hemolytic anemia. Dr. Sean Kane 20:42 And this is a really interesting one. And the reason it's interesting is that there's a blood test to look for autoimmune hemolytic anemia, which means that your immune system causes your red blood cells to lyse, and you become anemic because you destroy your red blood cells. Now this blood test is called a direct Coombs test, and it basically looks for the antibodies attached to your red blood cells that are associated with this autoimmune hemolytic anemia. So in patients that take methyldopa, about one in five (20%) will have a positive Coombs test, meaning that they do have the antibodies. But it's actually very rare, less than 1% will actually progress to having a Hemolytic Anemia caused by this autoimmune problem. So again, very commonly, the blood test to look for autoimmune Hemolytic Anemia will be positive, but the actual risk of getting Hemolytic Anemia is fairly low. So again, Speaker 2 21:31 we've gotten to this point where, rather than having a knee-jerk response to stopping the medication, you have to remember that. Again, we've got to this point because we've tried and failed so many other medications. And so really, I believe the best practice would then be to wait and see on only if they then manifest as the anemia, then we want to go ahead and get rid of the medication, but if they just have a positive direct Coombs test without anemia, that alone is probably not enough to stop the medication, because we're going to be losing another last-line antihypertensive. Dr. Sean Kane 21:57 And again, to get the 30,000-foot view: although methyldopa is commonly associated with antihypertensive treatment in pregnancy, many experts believe that labetalol or nifedipine XL may be equally safe and potentially more effective with a better adverse‑effect profile. So in pregnant patients, instead of automatically choosing methyldopa (a knee‑jerk reaction from training), consider labetalol or nifedipine XL as reasonable alternatives to methyldopa. Speaker 1 22:29 And that's a refreshing view, because, like you, we discussed with the beginning, all we had learned, and it was engraved in our brain, was methyldopa — think pregnancy — so it's good to have some other safer agents available to treat these patients. Speaker 2 22:41 All right, so I guess I get to be the one again, the third time I'm gonna address the third medication I'm introducing to you on minoxidil. So this one again, another old E, not as old as FDA approved back in 1979 and this one again, not first line due to lack of comparative data, specifically outcomes. But then really also, we're adding to the mix a nice, nasty ADR profile too. Speaker 1 23:01 So it is a direct vasodilator. So think about some of the other agents we have available. It's very similar to hydralazine, which is also causing vasodilation in the periphery and then reducing the blood pressure. Dr. Sean Kane 23:13 And you know, the dose here is typically taken once a day, although it can be taken twice a day, anywhere from five to 40 milligrams. 40 milligrams would be a very aggressive dose. So typically, when I see minoxidil, I'm seeing somewhere between five and 10 milligrams once or twice a day. And typically, because of the side effect profile that we're going to talk about, this is reserved for those really, really resistant hypertension patients or patients that can't tolerate most of our other therapies. So when I see minoxidil, I'm always thinking, why this patient must have either a lot of side effects to other medications, or they must have very impressive hypertension, all right? Speaker 2 23:48 So as far as what the side effects are, and one of the things it does, it's something unique, is as it starts working, it also triggers a baroreceptor response. And so what that then leads to is the body starts kicking in the sympathetic nervous system, so you see an increase in heart rate, and so tachycardia can occur. Dr. Sean Kane 24:04 Dr. Schuman, because of that tachycardic response in certain patients who have ischemic heart disease, especially, we worry about this antihypertensive agent causing angina, causing myocardial infarctions, things like that. It's actually a boxed warning that you know this can worsen angina, can cause ischemic heart disease problems. So for that reason, it's recommended that you combine minoxidil with something that blunts the sympathetic tone, such as a beta blocker or even a clonidine like drug to blunt the tachycardic response, so that you don't get angina, ischemic heart disease problems, things like that. Yeah, which gets Speaker 2 24:35 to the whole issue we were just talking about with alpha methadone phase. We get a bonus say, Oh, this is a great medication, but it has to be used in another blood pressure medicine. Well, pressure medicine. Well, if we were able to use that other medication in the first place, we wouldn't Speaker 1 24:46 be using this one, right? So kind of going along with the same theme, it causes more water retention, edema and weight gain. There is actually a box warning that it should be used with big doses of loop diuretics. So essentially, just like methyldopa, we're using two medications — and, as with the tachycardia side effect we talked about, we have to use another medication to tame the side effect of this one. So it's like putting the dog on a leash. You know, you have to kind of make sure that you keep it under control so it doesn't kind of go rogue. Dr. Sean Kane 25:17 And really, just think about this for a second. So what we've already established is that if you're on minoxidil, you have to be on a beta blocker or clonidine to blunt the tachycardic response. Almost always you will be on a loop diuretic. And in the packaging it even says two additional agents in addition to the loop diuretic. So really, you're thinking at least three agents before you even initiate minoxidil, potentially even more agents, depending on what those initial agents are. Again, this is for very treatment resistant hypertension after you've kind of used up a lot of your other drug classes. Yeah. Speaker 2 25:49 So again, it gets even more fun with other side effects. So we now look at pericardial effusion. Again, rarer, so maybe a 3% incidence, but again, a box warning here, it can even progress to cardiac tamponade as well. I believe that's even further rare, but then that's a big problem, and then those with tamponade may also have other risk factors besides being on minoxidil. So if these other things are true, CHF, renal impairment, severe edema, again, that's going to increase the risk Dr. Sean Kane 26:14 even further. Let's just be clear about what that is. So pericardial effusion is blood or fluid that accumulates around the heart, and a tamponade is where you get so much of that fluid, the ventricles can't fill up, and you get hypotensive potentially leading to cardiac arrest. So this is a big deal, where your heart can't fill up with blood because of all this edema, either typically from fluid, but could be caused by blood around the heart. That is a huge side effect profile. That is a big deal, and that's what warrants the box warning on minoxidil. Speaker 1 26:44 Well, talking about box warning, I think this side effect needed a box warning, but it does not, and that side effect is hypertrichosis, and basically it's the abnormal pattern of hair growth on ARM, legs, face and eyebrows, as well as head. And of course, with 80% incidence, it's a very high incidence within three to six weeks of using it, either in men or women. So just because you have estrogen floating around in women, it doesn't give any protective effect. And of Dr. Sean Kane 27:10 course, especially for women, this can cosmetically cause issues. For men, it may be advantageous, depending on how much hair they have on their head, but still, it's occurring everywhere in the body. And of course, especially for women, you can shave or use waxes, whatever you want to do to deal with the hair, but it still is a problem, right? Speaker 2 27:30 I'm sure there's a way to spin this to the positive benefit, though. What's the name of that one medication which we use to help with hair growth, Rogaine, same medication, isn't it? It is. Oh, wow, yeah. So again, we can spin it. And so we've also available topical formulation called Rogaine, yes, Dr. Sean Kane 27:46 so it's interesting that minoxidil, and this is a great way to remember this hypertrichosis side effect, is that we use Rogaine, which is minoxidil, topically, for this side effect. It's just that when you take it systemically as an oral tablet, you get this side effect everywhere, not just wherever you topically apply it. Speaker 1 28:04 So before we jump into talking about Rogaine, I just want to make sure — is this hair growth permanent, or does it go away? Dr. Sean Kane 28:13 So it's interesting. It takes, you know, between three and six weeks to fully kick in, and when you stop the drug, it takes about six months for your hair patterns to go back to whatever your baseline was. And again, in thinking about the topical minoxidil or Rogaine product, it actually is purported to have the same mechanism of action that it has for blood pressure, so it vasodilates The tissue that you apply it to, typically on the head, and that vasodilation increases blood flow and stimulates hair follicle growth for something like male pattern baldness. Speaker 2 28:45 So again, I think overall is a summary of this one. Lots of serious ADRs and boxed warnings. If you do see minoxidil on a patient profile, it's almost always an indication that the patient has severe, treatment-resistant hypertension. Dr. Sean Kane 28:57 or they're balding, or they're balding, correct? You know, in thinking about everything the last three medications we've talked about, typically, you're going to see this for these more resistant patients who have not been successful in their first line agents. It's not just about the medications. There's other things that we need to be thinking about, besides just adding on something new just because the blood pressure number is high, yeah, Speaker 1 29:19 and it happens very many times where physicians or providers keep on adding medication, but you really have to assess whether a patient is taking it at home. Is there a cost burden to it? Is there a pill burden that they're facing? Because we just talked about it, these agents are usually used twice, two, three times a day, and it's not easy. If they're already on five different medication yet you're adding three more doses in the day. Dr. Sean Kane 29:44 To be honest about the only benefit to these is that they're fairly inexpensive for the most part, with the exception of the clonidine patch, because they're so old, which could be a benefit. But again, pill burden is a really big deal, Speaker 2 29:57 and so again, we have to have been really look at some of these other reasons. Why somebody's resistant so again, compliance with existing regimens, to see if we need to do an education, enforcement of that, lifestyle modifications of baits, looking at the salt in the diet, looking at exercise, some of these other things as well. To do that have a much better side effect profile than again, many of these Speaker 1 30:17 rule out things like white coat hypertension. If they have any underlying etiologies like pheochromocytoma — where is all this output of adrenaline or norepinephrine coming from? — then use the mainstream antihypertensive medications first before opting for these last-line options. Dr. Sean Kane 30:34 So to kind of review, just to emphasize again, some of these first line agents that we should be picking because they have great clinical outcomes data, long term clinical outcomes data are thiazides, calcium channel blockers, ACE inhibitors and ARBs. These have the great data for them, and based on the ALLHAT trial with what we saw with doxazosin and lowering the BP number is probably not sufficient to select an agent for blood pressure management. We really want to see. Does it reduce your risk of heart attack, stroke, renal disease, things like that. Speaker 2 31:05 The first medication we talked about was clonidine. So clonidine, again, has a hypotensive effect, so can cause sedation, dry mouth, impotence, though, and bradycardia has adverse effects. It is available in oral tablet, typically twice a day, but also available in a patch that can be replaced once weekly. And really importantly about that, though, you can have a rebound effects withdrawal, like effects, if it is stopped abruptly, things like rebound tachycardia, hypertension, headaches, things like that. So again, really a good education if you're using it in the settings of acute alcohol abuse. Again, make sure that you're only using it only when it's needed and not on a scheduled basis if you can Speaker 1 31:43 avoid it. And then we discussed methyldopa, which is one of the three preferred antihypertensives for pregnant women. The other two commonly used agents are nifedipine XL and labetalol — they're equally effective and may have a more favorable side-effect profile for the mother. Dr. Sean Kane 32:01 The third agent was minoxidil. And really this should scare you in terms of the side effect profile, it has a number of box warnings, including tachycardia that potentially could lead to angina, edema that typically requires a loop diuretic in addition to it, and also pericardial effusion that rarely can lead to tamponade, which is a medical emergency. So again, when you see minoxidil, this should be a red flag that this patient either has a lot of side effects to existing anti hypertensive drug classes, or they just truly have very treatment resistant hypertension. So with that, that's episode 65 we're available at HelixTalk.com, on Twitter, at HelixTalk, we love the five star reviews we've been receiving on iTunes. It helps motivate us and helps identify topics that may be interesting to the audience. So if you haven't done so already, please do give us a five star review on iTunes with that, I'm Dr. Kane, I'm Dr. Schuman, and Unknown Speaker 32:55 I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 32:58 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 33:09 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.