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. This podcast Narrator - ? 00:11 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 of 118 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is cocaine and beta blockers absolute contraindication, or medical myth. So today, we're really going after whether patients who have cocaine use disorders should be completely contraindicated from ever having a beta blocker, or if this is a remnant of the past, and there is a lack of data to support that concern. Dr. Khyati Patel 00:59 And Dr. Kane that sounds like a century old question, so we're excited to present some evidence based information on either supporting or debunking this myth. Exactly. Dr. Sean Kane 01:10 So why don't we start with a patient case to kind of set the context for a typical patient scenario where this question could come up in So, Dr. Patel, imagine you go back to your p4 year and you have a patient who is admitted to the hospital. 55 year old guy comes in with chest pain, just like everyone else in the ED EKG is fine. He's admitted for a 23 hour observation, and you're part of that internal medicine team for the patient. So you take a look at him, you note that his troponin levels are negative. So he did not have an NSTEMI, no STEMI, nothing like that. He just had angina. Past medical history is he has heart failure with a reduced ejection fraction, or systolic heart failure. His EF is 40% and he does have a history of coronary artery disease. He had an MI a couple years ago and got a cardiac stent at that time. He does admit to regular use of cocaine on many weekends, and he is not interested at all in stopping cocaine, despite being admitted to the hospital for chest pain right now, he takes Lisinopril, but he does not take a beta blocker, and that's basically all of his cardiac oriented meds for blood pressure today, his heart rate's 75 blood pressure is fine at 130 over 80. And you decide, hey, Preceptor, I see that he has systolic heart failure. He's got a history of coronary artery disease. He's probably good candidate for a beta blocker. And your preceptor looks at you and just stares you down and says, are you insane? Don't you know that beta blockers are absolutely, unequivocally contraindicated in patients who use cocaine, and you'd never heard this before as a p4 and now your world is shattered that you apparently missed something really important in pharmacy school, and that's really the setting that we're talking about today. Is Is that really a thing, or is it something that has been propagated through decades and is something that really should be considered a medical myth. Dr. Khyati Patel 03:01 I think that's important for us to address today. I probably Dr. Kane, if you kind of put me out there, you know, few years back in a fourth year student position, I probably would believe what my preceptor had to say, but, but I think the right thing to do for anyone is to look into the evidence, right? So let's start with understanding the basics of, how does cocaine work? What's its pharmacology? Dr. Sean Kane 03:26 The way that cocaine works is that it's a sympathomimetic, so it increases adrenergic tone, it makes you have that fight or flight response. And it does other things too, but in terms of the cardiac effects, that's what's really going on, and it does that by being a dopamine, serotonin and norepinephrine re uptake inhibitor, which means that you have more norepinephrine, serotonin and dopamine in the synapse between your nerves. So in this case, we're mostly oriented or interested in norepinephrine, and that itself is a sympathomimetic catecholamine. So it increases your heart rate, it increases your blood pressure, it makes you more alert again. This is activating your fight or flight response. Dr. Khyati Patel 04:07 And so if we kind of look into more granular pharmacology, this norepinephrine is going to affect a couple of different receptors located in our vasculature, right? So we're talking about Alpha One receptors and beta two receptors. So when the nor epi binds to the alpha one receptor, it causes vasoconstriction. However, when it binds to beta two receptor, it does the opposite. It causes the vasodilation. So as the levels of nor epi kind of goes up, the alpha one is going to be predominating, and therefore the Alpha One mediated or resulting vasoconstriction is going to happen. Dr. Sean Kane 04:48 And really, you might ask yourself, Okay, so I understand having a patient have more norepinephrine will cause vasoconstriction, which will cause their blood pressure to go up. It almost seems logical that giving something that would decrease their blood pressure. Or shouldn't cause harm, right? So why is it that a beta blocker could potentially cause badness in these patients who use cocaine? Dr. Khyati Patel 05:09 So let's say a patient took the beta blocker right on the Alpha One receptor, the cocaine is still sitting, giving that vasoconstrictive effect, but on the beta two receptor, now we have the beta blockers, and those beta two receptors are now blocked by the beta blocker, meaning there is no effect of cocaine on those two beta two receptors, meaning there is no that opposite vasodilation happening. And so really, the concern here is that unopposed, quote, unquote, unopposed Alpha simulation leading to that overt vasoconstriction, and therefore a profound hypertension. Dr. Sean Kane 05:46 So in a way, Dr. Patel, this is like a paradoxical effect where you give an antihypertensive like a beta blocker, and instead of decreasing blood pressure, it actually dramatically increases blood pressure because of this unopposed Alpha stimulation, because we're blocking the beta two vasodilation pathway, right? That's correct. So I'm assuming that this probably comes up fairly commonly, given that cocaine can cause patients to have cardiac ischemia, hypertension, angina, things like that. And beta blockers are very commonly used for a variety of heart conditions that people who use cocaine may end up having Dr. Khyati Patel 06:20 Right, correct. And this common question about, can we use the two together? You know, comes up more frequently than we think of it. Obviously, we know that, you know, cocaine isn't good for the heart, so for our patient who presented the first attempt should be, well, you know, let's, let's have you stop it. He's not interested in stopping. So that's not the conversation for today. But the reason it's bad for the heart is because it does cause hypertension with the nor epid stimulation, and then can cause leading aginal effect because of the coronary vaso spasms. Dr. Sean Kane 06:53 What's interesting is that, you know, this is a very common Ed presentation, someone who used cocaine, or maybe they don't even say that they use cocaine and they come in for chest pain. In the literature, 95% of the time when someone comes in with cocaine associated chest pain, it is actually just angina. So only 5% of the time do they actually have a true mi in terms of in STEMI or STEMI, where they have troponin elevation, ideally, EKG changes suggestive of ischemia. That's the vast minority of the time that they actually have a true MI. 95% of the time these patients that have cocaine induced angina actually are not having heart attacks. We still will obviously work them up that way, but that's a fairly uncommon finding, actually, in patients who choose to abuse cocaine, Dr. Khyati Patel 07:39 right and then this kind of a presentation of acute angina, you know, like the first therapy we go to our beta blockers, right? So not only in Angel episodes, but pre existing CAD or even heart failure. And so, like you said, Dr. Kane, this scenario is fairly common, where we know patients who have underlying cardiovascular disease could be worsened by the cocaine use, and we know that they can benefit from beta blockers, but with the history that we know so far that we don't know if the beta blockers are safe or not. Dr. Sean Kane 08:13 And really, you know, in diving into the literature, Dr. Patel, there's kind of two common scenarios that have come out of the literature that we'll be answering today. So one common scenario is patient comes in with acute chest pain. Can you give them, typically, an IV beta blocker to acutely help with their angina and to acutely help reduce their blood pressure? That's kind of option A so it's more the acute situation. The other common scenario is, if someone has a history of cocaine use and they have heart failure, can you give them a beta blocker more of a chronic situation, so oral once or twice a day. Beta Blocker. Is that safe, knowing that they are likely to use cocaine in the future, so they don't have acute hypertension right now. But can you give it to them, knowing that at some point they may try cocaine again, and if they do that, are they likely to experience a very bad outcome from doing that? Dr. Khyati Patel 09:06 And these are very two important questions, right? Because one belongs to practice setting that you belong to, Dr. Kane, an acute scenario, and the other one is more chronic, where I kind of take place on the clinic side. But before you when we get to those questions, I think it's important to address some of the questions regarding this unopposed Alpha stimulation theory. So really, is it really that's happening pharmacologically, or is it just theoretical? What kind of evidence do we have? Does a type of beta blocker matter? We know we have many different types. We have beta one, selective beta blockers such as Metoprolol, or non selective beta blockers such as propranolol, and we do have some mixed beta blockers that have alpha and beta effect, such as carvedilol as well as labetalol, right? And so we need to dive a little bit more into details of this different types of beta blockers as we address those two questions. Sense. Dr. Sean Kane 10:01 So, Dr. Patel, when in doubt, it's time to go into the literature time machine and really figure out, you know, do we have answers to all of these questions that we have that has propagated into this kind of dogma of medicine that you can't do cocaine and beta blockers at the same time? So if we go into our time machine, Dr. Patel, we're going to go all the way back to the 1970s that's a long time ago, but that's actually where the story here started. So at that time, propranolol, which is a non selective beta blocker, was actually considered a treatment of choice for cocaine toxicity. And when I say cocaine toxicity, I mean someone who took so much cocaine that now they are hyperthermic, agitated, maybe even having seizures, angina. You know, this isn't your normal person taking cocaine and having fun. This is someone who took too much cocaine. Dr. Khyati Patel 10:51 So if I was in a toxicology class back in 1970 I would learn that an acute treatment for cocaine toxicity is propranolol. Dr. Sean Kane 11:00 That's exactly what you would learn. And you know, if you think about mechanistically, some of this makes sense, right? So if we're blocking some of these beta receptors, that means that the heart is not going to have as much of that beta one stimulation that norepinephrine also does, that we didn't talk a lot about. And you know, propranolol also crosses the blood brain barrier fairly well, so you're potentially going to block some of those adrenergic receptors in your brain that are causing the agitation and things like that. Now, in all fairness, it's well beyond the scope of today's podcast to talk about more modern therapies associated with cocaine toxicity, but suffice it to say that nowadays, the main two therapies are avoiding hyperthermia, so cooling off patients, typically surface cooling, and then two giving them benzodiazepines. So benzodiazepines are the treatment of choice for cocaine toxicity, not beta blockers. And you know that change. The reason that we don't use propranolol anymore is because of kind of what has happened historically after that in the literature. And really the first question mark came in 1980 so 1980 they took a bunch of monkeys and basically gave them lethal doses of cocaine, and they split them into different groups and gave different groups different drugs to see how different therapies could prevent the toxicity of cocaine. One of those therapies was propranolol. So something like three monkeys got propranolol plus cocaine. Three monkeys got cocaine with placebo, and then, you know, there were other drugs that were also tested. What happened was that in the monkeys that got propranolol, it did reduce heart rate and blood pressure. And again, if we're thinking about this unopposed Alpha theory, when we gave that propranolol to those poor monkeys, we should have seen hypertension, not a decrease in their blood pressure. But it turns out, in that study, all of the propranolol monkeys died with lower doses of cocaine that caused death versus some of the other groups, including the placebo group. So in other words, their outcomes were worse. In terms of these monkey patients, if they got propranolol with cocaine, that was worse than if they just got cocaine alone. And typically the way that they died was seizures. So really, propranolol was not neuroprotective in any way, but we did not see this paradoxical hypertension that we would have expected to see. So really, a lot of people have looked at that study and said, aha, monkeys that get cocaine, they do worse, therefore propranolol is harmful. But I would caution the audience to remember that we gave these poor monkeys toxic doses of cocaine and waited to have them seize and die. It just happened that their toxic threshold was slightly lower than if they hadn't gotten propranolol. Dr. Khyati Patel 13:31 And again, to emphasize that that worsening outcome was not the elevation of blood pressure, it was because of the seizures that were induced Exactly. Dr. Sean Kane 13:41 And you know, if we went five years later, 1985 that was the first human case report that really appeared. And this is where this paradoxical hypertension, unopposed Alpha thing, really took hold. So what happened was someone came in with cocaine associated chest pain. They gave them propranolol, and their blood pressure went from 170 over 118 to 180 over 140 so their blood pressure got higher, paradoxically, despite getting propranolol. Now, even with that, higher blood pressure patients did fine. They didn't have any side effects of that, and actually left the emergency department against medical advice, so there was no follow up done for the patient. Presumably, they did fine, but the fact that one patient got one dose of, in this case, propranolol, and the blood pressure got higher and not lower, really drove home this potential theoretical risk of this unopposed alpha. Dr. Khyati Patel 14:34 And then so five years later, in 1990 is when they actually did a prospective study in about 30 human patients. So again, this is not the monkey patients. These are human patients, and these patients received either combination of cocaine and propranolol and cocaine alone. So these were the two different groups, and they found that those who receive cocaine plus propranolol had a little bit. More vasoconstriction than those who used cocaine alone. The study findings were not replicable. However, when they they switched out the beta blocker, so instead of using propranolol, they repeated the study with using the labetalol and the findings were not the same. So there was no evidence for increased vasoconstriction, and Dr. Sean Kane 15:22 again, just to highlight, you know, this is interesting that it's a prospective study where we gave cocaine to people, which I think is fascinating in itself, but these were people that were taken to a cath lab, and then they used angiography to visualize their coronary blood vessels to see if vasoconstriction happened or not. So it's not like they look to see, did troponin increase? Did blood pressure increase? Things like that, they're specifically looking at in a cath lab, whether coronary vasoconstriction occurred or not. And again, if we're going with this theory about unopposed alpha, it would appear that maybe propranolol might do that. But if it does do that, it's mostly on these very small coronary blood vessels, as opposed to systemic circulation. Dr. Khyati Patel 16:01 So then, after 1990 we didn't have a lot in the literature. But then 2007 happened where we had a one patient case where patient had overdosed on cocaine, and the patient received IV Metoprolol. This is your beta one, selective beta blocker. And shortly after, the patient coded and died. That's a wow finding, right? And so it turns out, though, looking more into detail, the patient's blood pressure actually had improved after the administration of Metoprolol. So we didn't really get to see that unopposed Alpha effect that we otherwise would, and that would signify elevation of blood pressure, but that didn't happen. But the conclusion of this, this patient case, was the patient could have died from the actual cocaine related overdose or an MI. And it's actually shocking to see that the patient's cocaine dose was about 1000 milligram taken intranasally. And if we look at some of the comparable studies we discussed earlier, the studies used about two milligram per kick, or the maximum of 200 milligram dose off the cocaine. So you can't really compare one patient case where there was a massive dose of cocaine taken, versus the studies that did not use such massive cocaine doses. Dr. Sean Kane 17:24 Yeah, and again, it's an n of one in this 2007 patient case, and patients code all of the time and sometimes temporally, it would look like a drug that was given could have played a role in it, or maybe it actually didn't. It's really hard to say, with such a unique patient case where the patient truly overdosed on cocaine. And I would not consider this like the smoking gun that cocaine plus beta blockers equals death. And the reason for that is that really around the same time, in the early 2000s most clinicians kind of took all of this data and said, Look, we really shouldn't be doing beta blockers and cocaine, and it may be considered like an absolute contraindication because of this unopposed Alpha thing. And again, I just want to emphasize the level of data at that point. So there's total two prospective studies, very small, one case series and three case reports. You know, we've given some of the data here. There's a little bit more, but it's not like we have a wealth of data here really supporting this, this concern, and because of that, this had been in the early 2000s led to a variety of retrospective studies where they looked at patients who had cocaine use disorders based on self reported or even urine drug screens, and Then they compared those patients that got beta blockers versus did not get beta blockers, and looked at their outcomes. And the reason at this point that these patients were still being given beta blockers is really twofold. So one, unfortunately, patients are not always honest with us, and they may actually use cocaine but not tell us, so sometimes providers are unaware of their cocaine status. And then two, even, despite many providers considering this an absolute contraindication, not everybody's on board. This has been a controversial topic for many decades. So for the clinicians who disagreed that this was an absolute contraindication, they still continue to give beta blockers. Now we have a ripe avenue to come up with a study, a retrospective study. So really, the retrospective data looks at people who use cocaine when they're given beta blockers versus they're not given beta blockers. Is there a difference in their outcomes in terms of bad things happening from this unopposed Alpha stimulation? Dr. Khyati Patel 19:34 And some of the evidence we have from these retrospective study, Dr. Kane is answering our earlier question to look at the beta blocker use in this patients in acute situation versus the chronic use, exactly. Dr. Sean Kane 19:50 So there's a there's a couple different meta analyzes, and we picked two. They're both linked at our show notes at HelixTalk.com episode 118 The first thing we're going to talk about is. Is by Pham and colleagues in 2018 and this was a true meta analysis. They looked at five articles with about 1700 patients that presented to the ED with cocaine associated chest pain. And they basically then are looking at the acute use of beta blockers to control angina and maybe hypertension. And this meta analysis, they demonstrated that there was no increase in non fatal MI, no increase in all cause mortality among those that got beta blockers versus did not so again, out of 1700 patients, as opposed to just a handful of patients that we had with other data, this did not support beta blockers causing any profound risk related to a cardiovascular risk from unopposed Alpha stimulation. Dr. Khyati Patel 20:43 And then, similarly, the systematic review that was done by Mann and colleagues in 2020 so this is a little bit more recent one looked at 12 different articles. The N was about 2000 patients who had documented cocaine use disorder. So again, this is a chronic setting and heart failure, and they found actually that beta blockers were either protective, meaning beneficial in these patients who were using cocaine chronically, or neutral, meaning they did not produce any harm. For variety of different endpoints that these studies looked at, such as, you know, readmissions to the hospital, mortality, any other major adverse cardiovascular event. We call them as mace events. Dr. Sean Kane 21:26 And you know, this was not a meta analysis, so it's not like they had p values and things like that, but what they did do as part of their systematic review is look at all of the literature surrounding chronic use of beta blockers in patients with cocaine use disorders. And again, both of our main settings here, acute and chronic, we have way more data demonstrating that this is not a thing, that if it does occur, it is a very, very small risk, and we haven't really detected that risk when we actually look at larger patient data points for this. Dr. Khyati Patel 21:56 So then that brings us to our earlier questions about whether there are differences between different types of beta blockers, because we know, you know, it kind of adds more to the controversy already, not all beta blockers are created equal. Yeah. Dr. Sean Kane 22:13 So, for example, we have our beta one selective beta blockers. You know, Metoprolol is considered beta one selective at doses, especially at doses less than 100 milligrams a day, when you get to higher doses, sometimes these Beta Blockers can lose their selectivity. Atenolol would be another common example of a beta one selective beta blocker. And if you think about it, if the mechanism of harm here is that we're blocking the beta two receptor, which is the vasodilation component, really these beta blockers should not cause anything bad to happen, because they're not causing unopposed alpha, because we're blocking the beta one receptor, not the beta two receptor, which is the implicated receptor. So if anything, these should be perfectly fine to give in a patient who has a cocaine use disorder, that unopposed alpha should not be a big deal. Dr. Khyati Patel 22:58 And then we have the non selective beta blockers, such as propranolol, that's the most common one in this particular category, yes, as it's non selective, it's going to block the beta two receptor and the mediated vasodilation. So in theory, it could lead to the unopposed Alpha stimulation. Dr. Sean Kane 23:15 Then we have our alpha beta blocker combo products like labetalol and carvedilol, and these black alpha one, so they cause vasodilation, they block beta one and they block beta two. And really, we kind of don't know the answer here, but presumably that alpha one blockade may help if this is a thing in terms of this unopposed alpha, because now we're blocking that unopposed alpha by blocking the Alpha receptor as well as the beta two receptor. And again, we have, like almost no data anyway, for this unopposed Alpha theory. But even if we did have more data, presumably that alpha blockade could be helpful in this context. In addition to that between labetalol and carvedilol, what's also interesting is that the degree to which it blocks the Alpha receptor is different. So in terms of the beta versus the Alpha blockade. Carvedilol is about 10 to one, meaning that it's 10 times better blocking the beta receptors versus the Alpha receptors versus if you look at labetalol orally, it's actually a three to one. So it has much less beta activity compared to Carvedilol when you put it in the context of its alpha blockade, and then IV labetalol as opposed to PO, is actually kind of in the middle seven to one ratio. So Carvedilol PO is 10 to one. Labetalol PO is three to one, and then labetalol IV is seven to one. And you might be asking, Why would there be a difference between if you give it IV and orally? It probably has a lot to do with bioavailability and first pass effect, with giving it IV versus po but suffice it to say that, you know, these have a mixed degree of alpha blockade, and they're not all created equal in terms of that degree of alpha blockade. But suffice it to say that basically, almost all of the data we have is more specific to propranolol, that non selective beta blocker, and generally, we have really good data for carvedilol, labetalol, and metoprolol, that this is not a thing, that this is not a concern that we should be worried about. Dr. Khyati Patel 25:07 And so moving on from that evidence in primary literature, let's look at what some of these tertiary literature is saying, right? So what is the FDA guidance and some of the national guidelines, such as ACCA telling us, so if you look at the package insert, there is actually no mention of cocaine. So if a clinician were to start beta blocker in a patient who is using cocaine, there probably would be minimal legal liability. And on Dr. Sean Kane 25:35 top of that, you know, if you look at up to date as an example, where they don't have to wait for the FDA to mandate something in a package insert to update their articles up to date, doesn't even mention cocaine, either. So really, from a package insert standpoint, from an up to date standpoint, other tertiary references, this is not a thing. So again, as Dr. Patel mentioned, it's not like you're at high risk of medical, legal liability if you were to give a beta blocker to someone with cocaine use, because it's not anywhere in the packaging. It's not a warning, anything like that. Dr. Khyati Patel 26:05 And so what do our colleagues at AHA/ACC and then any of the guidelines are addressing this? Dr. Sean Kane 26:12 So their recommendation, it does come up in the 2014 unstable angina in STEM guidelines, and they basically say you can give an alpha beta combo blocker, like labetalol, it may be reasonable they say after cocaine use, if a patient is hypertensive or has sinus tachycardia, as long as the patient has received a vasodilator, and they specifically mentioned nitroglycerin or calcium channel blocker within the previous hour. Now this is a 2b recommendation, which means that they have very little data supporting those recommendation. And in my opinion, they kind of copped out a little bit. So they said, Yes, you can do it, as long as you give this other thing. And there's absolutely no data given this other thing, you know, prevents that unopposed alpha, theoretical risk or not. Now, with that said, someone who has chest pain that comes into the ED, unless they're on a PD five inhibitor, they're very likely to get a nitrate anyway, so maybe it's a non issue, but I'm not a huge fan of this, as long as they got a vasodilator statement, because there's literally no data that says that that should be there. And as it is, we have very little data supporting that we should even be concerned period about giving a beta blocker in these patients with cocaine use disorders? Dr. Khyati Patel 27:23 Well, that's very interesting, but I think we are ready to kind of make our concluding remarks over here. Dr. Sean Kane 27:29 So I would argue, you know, sometimes, and this is a perfect example, it takes, like, 10 times the effort to disprove a statement than the amount of effort it took to originally suggested, and it literally took a handful of monkeys in a monkey study and some other case reports to really turn this from a treatment of choice for cocaine toxicity all the way to an absolute contraindication, and now we have 1000s of patients that have indicated this is probably safe to do, and yet, that's still not enough for many clinicians to be convinced that it's a safe therapy. In my head, I'm thinking things like ethanol or alcohol with metronidazole or the brand name is Flagyl. You know, we all learned in pharmacy school that this is a total No no, that you can't even use mouthwash because you're going to have this disulfiram like reaction. You're going to vomit all over the place. This actually does not exist. We have plenty of good prospective data showing that alcohol plus Flagyl is not a thing, but yet it still is, this medical myth that gets propagated as we learn about disulfiram like reactions. Another common example would be hydroxychloroquine, azithromycin for covid 19. So this the study, if you will, that put this on the map. Was just a handful of patients. It was a low quality study, and now we have hundreds, if not 1000s, of patient data points demonstrating this doesn't do anything, and yet this is still kind of sold as a potential therapy for covid 19. Again, it's annoying to me that we have to have 10 times the effort to get rid of some of these things that get put on the map with just a paucity of data that really puts them there in the first place. Dr. Khyati Patel 29:07 And Dr. Kane this really emphasized the importance of evidence based practice, rather than listening to, you know, authorities without any scientific background, mentioning some of these, you know, false narratives that's coming out of studies that are not very high quality Dr. Sean Kane 29:27 100% and really, if you think about it, that's like the role of the pharmacist, right? So our job is to make sure that we understand the literature, we evaluate the literature, and then we form a conclusion based on that literature. We are the drug experts. This is one of our domains that we should take control of and make sure that we are playing that role as part of that interprofessional healthcare team. Dr. Khyati Patel 29:48 And so really, at the conclusion of this, there is very little, extremely little literature out there that supports this unopposed Alpha stimulation theory. And. In, you know, a few of the studies that are showing harm most of the time, in those studies, the blood pressure actually improved with the addition of beta blockers. So right then and there, it debunks the whole unopposed Alpha effect. Dr. Sean Kane 30:14 And you know, if we look at that retrospective data that we have, we have 1000s of patient data points showing no harm and even possible benefit, especially if a patient is indicated for a beta blocker, despite them having a history of cocaine use disorder, and presumably that they continue to use cocaine. So there's zero hint of harm in these studies, and most of that data is with IV labetalol for acute management. And again, labetalol has really never been implicated in these like lower quality studies, is causing unopposed Alpha stimulation and then Carvedilol for chronic therapy. Again, Carvedilol has never really been implicated in these other smaller studies of potential harm either. Probably we're using labetalol and carvedilol because they're alpha beta blockers, and that alpha blockade gives us some comfort that we're not as worried about that unopposed Alpha stimulation. But I would even argue Metoprolol is probably fine. Atenolol I don't like anyway, but sure if you wanted to use it, that's fine too. Really, the vast majority of the lack of data comes with propranolol, which is not even a commonly used beta blocker anyway, right? Dr. Khyati Patel 31:17 So I think if we ask the audience the question whether this is really true or is the medical myth, I think we're going to conclude that this really is a medical myth, although we know that not everybody is going to agree with us, as it is a controversial topic, but it was our duty to put forward the evidence that this myth was generated on and the decision is yours to make now. And you Dr. Sean Kane 31:44 know, if we went back to our 50 year old patient case where he came in, got admitted for 23 hour observation with chest pain, he has a history of coronary artery disease, cardiac stent and heart failure, he is absolutely 100% indicated for a beta blocker. So in our fictitious scenario of Dr. Patel being a p4 student, hopefully she would go back to that literature, evaluate the literature, and go back to that preceptor and say, Hey, I don't know if it really should be absolutely contraindicated. This is what I found. And I think in this context, something like Carvedilol would be a very reasonable option to give this patient, given that it has alpha beta blockade. If people are really worked up about that unopposed alpha and it's one of the three drugs that are appropriate, one of the three beta blockers that are appropriate for heart failure with reduced ejection fraction. Obviously, it would be great if the patient stopped using cocaine, but if he's not ready, you arguing or yelling at him is not going to make it any more likely that he's going to stop cocaine. So I think that in this circumstance, I would absolutely favor giving carved a lot to the patient. Dr. Khyati Patel 32:44 And I think I would agree with that conclusion as well. You know, looking at the patient, obviously his, his benefit with using beta blocker, with his history of having a previous mi as well as a reduced ejection fraction heart failure, kind of Trumps his. You know, weekend cocaine use that were you looking at if you put all the literature in the context here together? Dr. Sean Kane 33:05 Well, if you want to look more into the literature, you can visit us at HelixTalk.com this is episode 118 and we have references to the systematic review, the meta analysis, and also a really good review article in the topic that I encourage you to take a look at and make your own decision. You don't have to take our word for it. We're also on Twitter, at HelixTalk, where you can see pearls from past episodes and notification when new episodes come out. And we love those five star reviews in iTunes. We love reading the generous comments that readers have left us. And if you have any episode suggestions, feel free to email us as well. We love hearing ideas from the audience of what they would like to hear more of. So with that, I'm Dr. Kane Dr. Khyati Patel 33:43 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 33:47 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 - ? 33:58 to suggest an episode or contact us or 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.