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 135 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is top four medication Myths Busted. So today we're going through four different medication myths or misconceptions that have, for whatever reason, continued through decades of good evidence, saying that these are either not a thing or have been dispelled or disproven, but still are taught these are propagated myths that we're going to be busting today. Dr. Khyati Patel 01:00 And let me be honest. Dr. Kane, I think the list was much longer, but since we are so passionate about this, we're going to cap it at four, and then perhaps do a next episode on the other myths. Dr. Sean Kane 01:12 I think that sounds like a good idea. And you know, Dr. Patel, to be honest, we've actually had a number of episodes that have been myth busting type episode. So just to run through a brief list of some of those, if you go back to last episode, 134 we talked about hypertensive emergencies and how the term hypertensive urgency is really a misnomer or a myth in terms of there's no urgency in hypertensive urgency, Dr. Khyati Patel 01:36 and I believe in Episode 118 cocaine and beta blockers. You know, we found that evidence doesn't really support that there is a real contraindication between people using cocaine and them being on Dr. Sean Kane 01:49 beta-blocker. Yeah, and if we go back to 104 when we talked about the GINA 2019 asthma guideline update, mind blown that albuterol is no longer the preferred rescue inhaler for those 12 years and older. I would say that that was a myth in the sense of we had very little evidence supporting the use of albuterol. As we got new evidence having, you know, an ICS-formoterol combination being the preferred rescue inhaler for those patients. Very interesting and certainly a cutting edge thing that is going to be hard to be hard to bust that myth moving forward, because albuterol is, you know, so predominant in in PRN asthma recommendation. Dr. Khyati Patel 02:28 And then episode 92 we talked about using or why we shouldn't just call it the normal saline. It does come with some issues, such as nephrotoxicity, and so use of the lactated ringers for IV fluid supplementation might be preferred in certain situations over normal saline. Dr. Sean Kane 02:48 And then finally, if we go all the way back to Episode 10, we talked about some of our pet peeves, one of which was, leave albuterol, how it's kind of a myth that it has a less tachycardic effect compared to albuterol. If there is an effect, it's a very minimal effect. And this is a couple, you know, a handful there. We've gone through a number of others. The intent of today's episode is specifically to focus on these four myths that we've come up with. And again, there's plenty more out there. And what's interesting, because these are myths, that means that these belief systems have been propagated over years or even decades. It's actually really hard to disprove these myths. It almost feels like you have to have 10x the amount of literature to disprove a myth, compared to the amount of literature if it ever existed to propagate the myth in the first place. So for that reason, we actually have six different references cited at HelixTalk.com Again, this is episode 135 to basically support, you know, the dispelling of some of these myths that we're Dr. Khyati Patel 03:46 going to talk about. So Dr. Kane, without further ado, let's start it. Let's get started with the first one. And I think this one is probably the most notorious myth, and the questions we get from patients when they're put on this medication, it's and it's metronidazole, brand name Flagyl, and alcohol interaction. Dr. Sean Kane 04:06 And basically, the myth is that if you have any alcohol with your metronidazole, that you're going to vomit feel terrible, that you're going to have this disulfiram like reaction. And therefore the recommendation is avoid any form of alcohol, including mouthwash, when you're taking Flagyl. And actually, the package insert for the FDA says, and I quote, alcoholic beverages should not be consumed during metronidazole therapy and for at least three days afterwards because of abdominal cramps, nausea, vomiting, headache and flushing. And again, this is called the disulfiram-like reaction. And this is 100% false. Dr. Khyati Patel 04:43 So let's learn what disulfiram is. It's basically a drug that is used to help with alcohol abstinence. Basically, when you drink alcohol, it gets converted to the acetaldehyde, which is that toxic and unpleasant thing that causes this reaction into acetate. And this reaction from acetaldehyde to acetate is facilitated by an enzyme called aldehyde dehydrogenase, and the disulfiram actually blocks this enzyme, and so it ends up increasing this unpleasant substitute called acetaldehyde, and that's what causes this cramping, nausea, vomiting and headache. But the reason we associate metronidazole to this reaction is that for a long time, we thought that metronidazole also blocked this enzyme, just like disulfiram did, and that's why, you know, it is included. What's Included in the package insert. You read off Doctor King, yeah. Dr. Sean Kane 05:43 And you know, for the longest time, we had a case report here or there saying that someone was intoxicated, they got Flagyl and they threw up, or that they felt terrible, or they had bad cramping. And it really wasn't until 2002 that we had basically the best evidence investigating this particular interaction between ethanol or alcohol and metronidazole, and this is cited in our show notes. So it's in 2002 they took 12 healthy volunteers, and they randomly, blindly gave them either metronidazole or placebo, then everyone got some alcohol, roughly speaking in terms of how much they had, they had about 20 ounces of a 5% beer, or the equivalent amount of the alcohol that you would get from that. And they, again, the participants didn't know if they had Flagyl or if they had placebo. And they monitored these patients after they gave them the alcohol. And what happened was they looked at subjective data, objective data, they even drew acid aldehyde levels in their blood, and basically there was absolutely no difference. And the subjective or objective data no adverse effects. Among those that had alcohol plus Flagyl and those that had placebo plus Flagyl, there's absolutely no difference there. Dr. Khyati Patel 07:00 So that was 2002 Dr. Kane, now fast forward to the 2021 there's actually a new CDC sexually transmitted infections guidelines, and in this guidelines, they're saying that to this day, there is no in vitro study, no evidence from animal models or clinical study that provide any convincing evidence that this interaction truly exists, and they really think, like you said earlier, Dr. Kane, that this reaction probably really happened because of alcohol alone or metronidazole alone, and not necessarily from the interaction. Dr. Sean Kane 07:34 Yeah, and if you think about it, what do people do when they get really drunk, they throw up, or what do people have when they take antibiotics? Sometimes they can have abdominal cramping. So there's no clear evidence of this interaction and these kind of anecdotes of someone that accidentally had some alcohol with metronidazole and they they threw up. There's so many other reasons that they could have thrown up. And again, going back to that 2002 study, we have really good randomized, double blind trial data showing that this is not a thing, at least in those 12 healthy volunteers. And for that reason, the 2021 STI guidelines, and I quote say, thus refraining from alcohol use while taking metronidazole is unnecessary, right? Dr. Khyati Patel 08:15 And this is probably a good advice to give to those one off patients who you know have to be on metronidazole. They're not on any other medications. You know, they're gonna go out and have a glass of alcohol over the weekend if they're partying and stuff. And you can say it's okay to do that. Obviously, you know if you have other patients who are using metronidazole in addition to other medications that could interact with alcohol, let's say Warfarin or some CNS depressants, then obviously your answer is going to be, yeah, avoid alcohol, because it interacts with the other months too. Yeah. Dr. Sean Kane 08:49 And if you think about it, you know who, who is going to be taking metronidazole? Someone who is either taking it for prophylaxis or that they have an active infection, those patients, as they're, you know, medically sick probably should not be getting drunk, right? They have bigger fish to fry in terms of getting healthier, but we also shouldn't be scaring these patients into saying, no alcohol containing mouthwash, you can't have a sip of alcohol, otherwise you're going to vomit all over the place. That's not a thing with this. And we need to kind of step back our recommendation with that, and acknowledge that excessive alcohol in all circumstances is not appropriate, but at the same time, we shouldn't be super scared of this metronidazole alcohol interaction. It's not as big of a deal as it's been made to be over many, many decades. Dr. Khyati Patel 09:35 I 100% agree, and with that, Dr. Kane, the second myth, probably I'm biased, but will be my favorite one, and that's about statins, that statins are not hepatotoxic, and the routine monitoring of the aminotransferases is not necessary. Dr. Sean Kane 09:55 Dr. Patel, this blew my mind, because when I was in pharmacy school, I learned. That upon initiation of a statin, you check some Cpk levels and lft liver function test levels. You do it four to 12 weeks after initiation, and I learned that statins were hepatotoxic, and we have to be mindful of that. This really blew my mind in terms of where the evidence is supporting the fact that, again, this is more of an overblown thing versus something that routinely happens, right? Dr. Khyati Patel 10:25 And if you think about it, Dr. Kane, you know from that 2003 guidelines for lipid management, we're actually not updated until this decade. It took them a decade to really update it. So then that all that evidence for the 10 years that was mounted in the 2013 that's when they realized that really, this is not a thing. We have 10 years worth of data showing that this lft elevation is a lot minute than we originally believed. So that's why I took a little longer. And then this 10 years, people kept practicing drawing out of teas, because that was the recommendation. And now, just like you said, it's taking a lot to undo this myth. Dr. Sean Kane 11:07 And you know, for the skeptical listeners, as I was, I would refer you to a 2010, American Journal of gastroenterology editorial that we have cited on our website, HelixTalk.com and you know, we're going to go through some of the details of that, but a couple things that that editorial talks about are things like, you know, when we talk about transaminitis or liver function tests that are above normal, generally, we say that, you know, anything three times the upper limit of normal is considered elevated LFTs. And this is more or less an arbitrary made up threshold. Of course, if your LFTs are sky high, that is not good. But in terms of three times the upper limit of normal being, like our magic threshold, that that means that they have some liver damage, is kind of an arbitrary made up threshold. Dr. Khyati Patel 11:56 And you have to keep in mind, you're look you're looking at a number, and a number is not really a disease, unless you put that in context with something that patient is coming with, like a symptoms that they're associating with, maybe malaise or fatigue, you know, pain in the upper right hand quadrant and Dr. Sean Kane 12:14 things like that. And you know, just to add on to that, just because a patient's LTS are more than three times the upper limit of normal that doesn't necessarily mean one, that they have hepatic damage, or two, that they're at risk for kind of acute liver failure or something more serious. You know, in clinical practice, when we see patients with elevated LFTs, oftentimes the knee jerk thing is to reduce the statin dose, stop the statin or change the statin. And what's interesting is that if you don't do that, if you just keep the patient on the same statin, in the vast majority of cases, those LFTs will actually return to normal, unless there's some other underlying cause of why those LFTs were increased. But nine times out of 10, it's not the statin that is going to cause a permanent change in those LFTs, Dr. Khyati Patel 13:00 and as the lipid levels are getting normal, there is slight transient lft increase that can happen, but that's not necessarily a direct sign of liver damage, yeah. Dr. Sean Kane 13:14 And that was the thing that really was fascinating to me, Dr. Patel, is that there are a number of proposed mechanisms why lft numbers might go up when you initiate a statin therapy that aren't related to direct hepatic damage. And the main proposed mechanism is that that's part of the body's normal or natural response to changes in cholesterol. And the reason for that proposed mechanism is that we also see changes in LFTs from other cholesterol lowering drugs that you wouldn't expect to have implications with liver function tests, for example, bile acid sequesterance, which are basically sponges in your GI tract that soak up cholesterol so that your body doesn't keep it in its blood. Even bile acid sequestering are associated with lft increases. And again, the proposed mechanism there is that it's a cholesterol thing and not a drug thing, which I thought was very interesting, Dr. Khyati Patel 14:08 yeah, and bile acid sequestrants are the same thing. You know. It doesn't even work in the liver. It works in the GI tract, but in the parietal area. And it's the same mechanism for why the LFTs may elevate. So clearly, this is not completely related to statin. Perhaps it's the overall cholesterol lowering. Dr. Sean Kane 14:30 Yeah, and you know, to put a number to it, in typical clinical trials of statins, the incidence of LFTs being more than three times the upper limit of normal it varies, but we're looking at roughly 1% or a little bit less than 1% so this does happen, and if you routinely monitor it, roughly, you know, one out of every 100, or one out of every 200 patients, you're going to see this transient increase in LFTs. But the question is, does that clinically matter, and should you do something different with with your statin as a result of that? So in 2006 Dr. Khyati Patel 15:00 National lipid Association. That's another association that puts out, you know, guidelines for lipid management too. Its safety task force did a publication we have that in the show notes. And basically this task force was comprised of some hepatologists, and they concluded that, as a matter of fact, statins do increase all of these even though this is a small increase. But the idea behind that was that this asymptomatic increase in LFTs were not really associated with this glorified liver injuries, you know. And like we mentioned, there are some probably other mechanisms that could raise the LFTs, and that lft elevation is not necessarily associated with liver injury. Dr. Sean Kane 15:45 And what I really thought was interesting out of that kind of statement from that task force was they said, If hepatotoxicity does exist in terms of statins directly harming the liver in a way that it causes symptoms for a patient, that risk, if it does exist, we're looking at roughly one out of every million or two out of every million patients that are given a statin. So if that hepatotoxicity risk is actually there, the actual risk itself is incredibly low. We're talking one to two incidences per 1 million patients that receive a statin. Dr. Khyati Patel 16:20 So in 2018 ACCA said, Okay, we're just gonna delineate, you know, a couple of different pathways for the clinician. So this is forever resolved. And they said in patients who are on statin and exert clinical signs of hepatotoxicity, so not just laboratory elevation, but clinical signs, then we should go ahead and check the LFTs. Now, this would make sense in patients who are not taking statins too if they show any signs of hepatotoxicity, we're going to go out and run a liver panel. What they said, though, in patients who are taking statins and they don't have any signs of hepatotoxicity, then you don't need to keep doing routine measurements of LFTs, again, this asymptomatic increase we talked about the three, you know, times the upper limit of normal. That arbitrary threshold is pretty rare, as you concluded to Dr. Kane, you know, really statin shouldn't be held as contraindicated agents in somebody who has chronic, stable liver disease, and in some cases, those with non alcoholic fatty liver disease. For example, statin is actually beneficial to reduce that inflammation. Dr. Sean Kane 17:32 And really, you know, Dr. Patel, the main patient population we are concerned with would be the acute, decompensated liver disease type patient. And to be honest with you, it wouldn't even make sense to initiate a statin in this kind of more acute setting, anyway. So again, I think the take home point here is in that stable liver patient, you can safely give a statin to that patient. They're definitely not contraindicated. You might monitor them slightly more often. But aside from that, there is no reason to withhold a statin in that patient population. And just like with our metronidazole example, the FDA package insert has in some ways, propagated this myth over time. You know, when statins first came out, we did have more monitoring of them because they were new drugs. So in the early 2000s most of the package inserts for most of the statins said that you should check LFTs before initiation of therapy, and then either semi annually check LFTs or after 12 weeks of starting the statin, or after changing the dose of a statin. Now you know, 20 years later, most of the package inserts as they've been updated over time by the manufacturers now recommend LT monitoring when you start therapy, and then quote when clinically indicated. So with that in mind, we're thinking checking LFTs when someone has some sign or symptom associated with hepatotoxicity in which you're clinically worried about the patient. This, in other words, is not something you routinely monitor. Dr. Khyati Patel 18:57 And Dr. Kane this over the years has become my pet peeve, especially teaching this topic to students in the classroom, I keep telling them, You don't have to do lft monitoring. And yet I receive care plans and recommendations from, you know, the clinic volunteers and stuff, saying, Oh yeah, we have to routinely check that. And I guess, you know, maybe the instructions in the classrooms are not heard properly. But this evidence is definitely eye opening, and I think a part of it, it's coming, because they're used to seeing patient get at least annual, you know, lft as part of their CMP panel. If you are individual that is going to your family doctor, and they do once a year, laps for the physical, a cmp or BMP, plus, you know, liver panel might be included as their routine, and you're going to have availability of lft. So they're not necessarily drawn because patient is on a statin therapy. They're drawn as a routine monitoring for physical. Goals in general. Dr. Patel, I Dr. Sean Kane 20:01 feel like that's like almost a hallmark of a wonderful myth that needs to be busted is that it is just propagated, and something that is so common, despite teaching it, despite guidelines telling you you don't need to do it, it's still done, and that's one of the reasons that we're talking about it today, right? Dr. Khyati Patel 20:19 Yep, exactly. So. Dr. Kane, they know overall, this issue of lft elevation happens to a very fine degree. However, there there are some there's some evidence, example, the SAGE trial, or the pooled analysis that's done under atorvastatin as the active statin agent, do show that the higher doses of atorvastatin, the 80 milligrams, might be associated with a little more increase in LFTs compared to the lower doses. So something to keep in mind. But again, not all patients are on other statins, and not all patients are on, you know, higher dose of atorvastatin. So for most patients, this routine monitoring is not recommended. And if you Dr. Sean Kane 21:05 think about it, Dr. Patel, if you initiate that patient on atorvastatin 80, if you don't check the LFTs, because you read the guidelines that say you shouldn't routinely check them, as long as the patient has no symptoms, you would never know if they have this transient increase in LFTs or not. So as long as you follow the guidelines, in lieu of having some clinical symptom, you wouldn't even know that that's going to happen for that piece, exactly. So I think it's time to move on to number three, and we're moving into the infectious diseases world again. And the myth here is that bactericidal antibiotics are better in some way than bacteriostatic drugs. And this is a complete myth. It does not matter if the antibiotic is bactericidal or bacteriostatic. There are a number of other facets that do matter, and that should be driving our decision point in terms of which antibiotic Dr. Khyati Patel 21:54 to pick. And I think the confusion or the myth really comes from these words and what they mean. And so bactericidal antibiotic cital means killing the bacteria outright. And these are kind of the drugs that rupture the cell wall or block the cell wall synthesis, such as beta lactams on the flip side, bacteriostatic, the word static means it halts the bacterial growth. But the concern here is that the true death of the bacterium really requires sufficient immune response, and in some cases, this bacteriostatic antibiotic needs to be dosed at a higher concentration in order for us to have that effect. And the drugs that are bacteriostatics are things such as your macrolide antibiotics like azithromycin, tetracyclines (usually tigecycline), linezolid and Bactrim. Dr. Sean Kane 22:52 So intuitively, Dr. Patel, it would make intuitive sense that of course, you'd want to pick the bactericidal drug, the one that kills the bacteria, instead of the static drug that just makes it not grow anymore. And in fact, if you look at some guidelines that have been published over time that have propagated this myth, they sometimes have recommended historically that the cidal drugs should be preferred over the static drugs. And someone who is severely ill or someone who's immunocompromised, where perhaps their immune system can't, kind of mop up the the bacteria that are just being inhibited from growing, as opposed to dying from the antibiotic that we give them, right? Dr. Khyati Patel 23:27 And I think, you know, the concerns we want to talk about, or issues we want to talk about is, like I said, the bacteriostatic drugs, they actually help kill the bacteria; they just need a little bit of a higher concentration. And then really, this definition of static versus subtle is more on the in vitro testing and not really what's their behavior in vivo. And the in vivo behavior really is confounded by a person's own immune response as well, like we mentioned earlier. Dr. Sean Kane 23:58 And even if you think about like, what is the definition of static versus siteal? The formal definition is that the amount of drug concentration that you need to kill the bacteria, which is called the minimum bactericidal concentration, or MBC, that that needs to be a fairly small number compared to the mic the minimum inhibitory concentration. So officially, the ratio of those two is supposed to be four times or less, meaning that you need no more than four times the mic concentration in order to cause bactericidal effects. Again, just like three times the upper limit of normal with LFTs a 4x difference to make up that definition for a cital drug is arbitrary. Why not 5x or 3x or 10x we've come up with this arbitrary system of what is static versus cital. And on top of that, what makes it even more complicated is that even how you test it in vitro, in terms of which culture media you pick, that can impact whether a drug is static or societal and also the dose that you pick. Aminoglycosides are a great example if you pick. A big dose of aminoglycoside, we consider it cytal, but if you pick kind of a more conventional dose of an aminoglycoside, we consider that static. So there are so many facets to this that don't make a clean distinction between static versus cital. Dr. Khyati Patel 25:12 And so the little evidence that we have is from these two systematic reviews, meta analysis that were published in 2015 and 2018 again, we have these citations in the show notes, and these were done in patients who had infections such as pneumonia, some intra abdominal or skin and soft tissue infections. And what we found is that really in curing these infection, there was no difference in efficacy between the cidal or the static antibiotics. The end point that these systematic review and meta analysis looked at were clinical cure rate or the mortality rate. And in this population, again, these antibiotics, cidal versus static, did not have any difference in efficacy. Dr. Sean Kane 25:56 And what's so interesting about this text for tell is, if you go to those articles, and you look at some editorials that have been published responding to those, the myth still propagates. And the reason for that is that we have very little evidence for things like endocarditis, meningitis or neutropenic patients. And the myth still persists that perhaps these patients need that cidal drug instead of the static drug, and we just don't have enough evidence to prove or dispel the myth. So this is still going to be out there. But of the data that we have, there is zero data showing that a cidal drug is better than a static drug as a chemical characteristic of the drug, terms of efficacy in treating a bacterial infection. Dr. Khyati Patel 26:38 So all in all, really, this distinction between, you know, cidal versus static is, by definition, and, you know, needing a bacterial cidal drug is, it's not really a thing, you know. You gotta have to consider other factors of the antibiotics, such as, you know, the volume of distribution, the site of action, or is, where does this antibiotic need to go, the dosing in itself. So rather than thinking cital versus static, those other properties of the antibiotic needs to be considered. Dr. Sean Kane 27:13 And you know what? Dr. Patel, in many, many disease states we we don't clinically draw the distinction between static and cital. What we do instead is that we observe literature that we have, and we review that literature to look at for a given disease state when we've had head to head comparisons of antibiotic x versus y, what does the evidence show in terms of what is the preferred more efficacious, more safe therapy? So for example, for MRSA pneumonia, we have data for what is the preferred therapy for Legionella, pneumonia or endocarditis, whatever those guidelines are based on evidence that have looked at, typically head to head comparisons or retrospective analyzes of data that we do have, and that's how we decide what is the best antibiotic, not based on a specific drug Property of static versus societal, right? Dr. Khyati Patel 28:01 And that's your in vivo evidence right there, right? And that's what we should consider, yeah. And so moving on, Dr. Kane, I think the last one, the myth that we want to burst, and I think we have covered or touched it a little bit in our episode 10, is the sulfa allergy myth. And the myth is that, you know, if you have a label that you are allergic to sulfa drugs, that you're allergic to any other non antibiotic drug that has a sulfa moiety, and that's just is not true. Dr. Sean Kane 28:31 So you know, Dr. Patel, this myth is, I'm I'm sure at least one of our listeners, this has come up where you're a new graduate in a pharmacy or a new prescriber, and you're either reviewing a prescription or prescribing a medication, and the electronic health record that you're using pops up this big alert screen that says, hey, this patient has a sulfa allergy. You can't give them furosemide because furosemide has a sulfonamide moiety to it. And I'm sure that there's at least one listener, a pharmacist as an example, that on their first day of the job, they freaked out. They called the provider and probably got chewed out by the prescriber, saying, This is not a thing. Don't worry about it. I'm sure this has happened, right? Dr. Khyati Patel 29:12 The other day, I got a provider saying, hey, I'm trying to prescribe to the patient and it's showing a flag. What should I do? And I said, go ahead and prescribe, because that's not a right thing. You know exactly. Dr. Sean Kane 29:24 So basically, the the issue here is that when we say sulfa allergy, sulfa actually means sulfonamide. So sulfonamide is that you have a functional group and on a chemical structure of a drug. This is an so two NH, two moiety, and this is a common component, a common moiety, of a lot of drugs in the market. And as we said, many electronic health records are sensitive, meaning that they produce an alert or an error message to a prescriber or to a provider that says, hey, they have a sulfa allergy against sulfonamide allergy. And this other drug that is. Not a sulfa antibiotic, but you know, some drug that has a sulfa component to it that there may be cross reactivity. And you know, if a patient is allergic to sulfa, they might also be allergic to furosemide or lasix as an example. There's a bunch of other examples out there, but typically this myth is propagated because the electronic health records are producing this error that makes everybody freak out, right? Dr. Khyati Patel 30:22 And I think there needs to be a distinction between antibiotic and non antibiotic that have the sulfonamide moieties, right? So 99.9% of time when we have somebody that says they have they have sulfa allergy, that means that they have sulfa allergy to an antibiotic such as Bactrim, and they, you know, had an allergic reaction to it. But there are other sulfa antibiotics that aren't commonly used. So Bactrim is the main antibiotic that you're using. And, you know, people have allergy that's, that's where it's coming from. Dr. Sean Kane 31:00 And you know, historically, we've just simplified it to say sulfa allergy. And the reason that that matters is that it's more than just that sulfonamide moiety. So these sulfa antibiotics, Bactrim, being sulfa methoxazole, trimethoprim, the sulfa methoxazole is what we're focusing on. You know, those antibiotics that are sulfa antibiotics have more than just that sulfonamide moiety to them, and I'm going to mention a few things. And Dr. Patel, I'm going to be really honest with you, my med Chem is a little bit rusty, but for those that are more familiar with med Chem, I can tell you the differences between a sulfa antibiotic and a sulfa non antibiotic are that those sulfa antibiotics have an aromatic amine at the end four position, and a five or six membered ring at the sulfona Amido in one position. And these non antibiotics typically don't even have an aromatic amine at all. So I can't tell you beyond that, but I can tell you that it's not just a sulfonamide moiety itself, but there's other things connected around that sulfonamide moiety that are important from the perspective of the immune response in terms of an allergic reaction, and that happens with sulfa antibiotics, but does not happen with sulfonamide non antibiotics, right? Dr. Khyati Patel 32:11 And so then you may ask, but what are these non antibiotic drugs that have sulfonamide moiety? Well, we mentioned furosemide earlier, but loop diuretics such as furosemide, torsemide and bumetanide have it, whereas one loop diuretic doesn't have it. Dr. Sean Kane 32:27 And this is the most common pimping question that I can think of, Dr. Patel, and it's annoying because it doesn't matter. When I say it doesn't matter, it's that we don't care that furosemide has a sulfa component to it, versus this other particular one does not, because, again, the presence of that sulfonamide moiety doesn't matter from an allergy perspective, correct? So the answer to that kind of silly pimping question is ethacrynic acid. So ethacrynic acid is the only loop diuretic that does not have a sulfonamide moiety to it. With that said, if someone has a true allergic reaction to furosemide or torsemide or bumetanide. Sure, you could probably give them ethacrynic acid, but you wouldn't specifically pick ethacrynic acid because they have a sulfa allergy. You just give them furosemide. Dr. Khyati Patel 33:13 But the other agents that are non antibiotic, that contain sulfonamide moiety are another type of diuretics, the thiazide, such as hydrochlorothiazide or chlorothalidone celecoxib, which is Celebrex, is another one. And this one I get all the time asked in my clinic is sulfonylureas such as glyburide and glimepiride. Dr. Sean Kane 33:33 And like you said, Dr. Patel, there's a number of others out there as well. You gave the example of Flomax or tamsulosin. There's a ton of them, and for the most part, providers would have no clue that this is a thing, if it wasn't for those Uber sensitive electronic health records that are propagating this myth, because they have a library in them of what drugs are, sulfonamide containing drugs, and they connect that up to that sulfa allergy. Dr. Khyati Patel 33:57 So really, the evidence we have does not support that there is any cross reactivity between the sulfa, which is the antibiotic based allergy, to the non antibiotic sulfa drugs, such as the furosemide, again. So there is no evidence whatsoever. Dr. Sean Kane 34:14 And this was actually specifically studied in a 2003 retrospective article that is cited on our website. And what they did was they took people who had sulfa allergies and then followed them electronically and looked to see when they got a sulfa containing non antibiotic, did they have allergic reactions or not, compared to a variety of control groups that were part of that study. So compared to those that did not have a sulfa allergy, those that did have a sulfa allergy were actually 2.8 times more likely to have an allergic reaction to a sulfa, non antibiotic. So what I mean by that is, if I have a sulfa allergy to something like Bactrim, and I take a medication like furosemide, my risk of having an allergic reaction. To furosemide is 2.8 times higher than someone who doesn't have a sulfa allergy. So at face value, Dr. Patel, that sounds really bad. Meaning, wow, 2.8 times more likelihood that seems like I probably shouldn't get that furosemide, because my risk of an allergic reaction appears to be higher. Dr. Khyati Patel 35:15 However, if you compare allergy to penicillin antibiotic, there's 3.8 times more likelihood to have an allergy, and there is not even any cross reactivity between sulfa drug and penicillin. Dr. Sean Kane 35:31 So basically, what we're saying here is that if you have a sulfa allergy, you are more likely to have other allergic reactions compared to someone who doesn't have a sulfa allergy. So for example, penicillin, you're more likely to have a penicillin reaction. And we know chemically, there is no cross reactivity there. So these patients with allergies are predisposed, in general, to have more allergies to other medication classes. But it's not because they have antibodies to a specific moiety that then has this really high cross reactivity rate. Very interestingly, in that same study, they compared those that had a history of penicillin allergy versus those that had sulfa allergy, and what happened when they got a sulfa containing non antibiotic like furosemide. And actually, the presence of a sulfa allergy was better, more protective of not having an allergic reaction to the furosemide or the thiazide compared to those with penicillin allergy. So again, this myth is dispelled in the sense that there is no direct cross reactivity from an immune system standpoint if you are allergic to sulfa, and then you get something like furosemide or a thiazide diuretic or something to that Dr. Khyati Patel 36:36 effect, right? And it's always good to investigate what kind of reaction they had to their sulfa antibiotic when there is a label that they are allergic to sulfa drugs. If it was rash, you could definitely go ahead and prescribe a non antibiotic sulfa drug, such as furosemide. But if the reaction was a little bit severe, such as Stevens-Johnson syndrome or TEN (toxic epidermal necrolysis), in which case you might have to educate the patient to continue monitoring symptoms. Dr. Sean Kane 37:06 And you know, Dr. Patel, my overall conclusion here is one, those alerts need to be shut off on these electronic health records. But two, anyone who has especially multiple drug allergies on their profile, they do have a predisposition to having a higher likelihood of other allergic reactions to other new drug classes that they've never been exposed to. So when you have that patient that has five allergies on their profile, when you give them something like a penicillin or sulfa drug, or anything that we know has the risk of an allergic response or a higher allergic response risk that patient with the five allergies is going to be more likely to have an allergic response versus someone who has no known allergies at baseline. Dr. Khyati Patel 37:48 That that concept definitely makes sense. Dr. Sean Kane 37:50 Well, why don't we just briefly summarize some of our four medical myths? And I would really encourage our listeners to find us on Twitter, we're at HelixTalk, and send us a couple of your medical myths that you think that we should be dispelling. So to summarize, our first myth was the metronidazole or Flagyl and alcohol interaction. This is not as big of a deal as it's been made out to be in the literature. And you know, there's good evidence that this is not a thing. There is no disulfiram like reaction with metronidazole. Dr. Khyati Patel 38:19 The next one is about statins. Statins can cause transient elevation in liver function enzymes. However, these these elevations are not necessarily associated with hepatotoxicity, and therefore the routine monitoring for the L of TS is no longer recommended unless obviously your patient has signs or symptoms of hepatotoxicity. Dr. Sean Kane 38:43 Number three was that bactericidal versus bacteria. Static classification of antibiotics is irrelevant. You don't have to pick a cidal over a static antibiotic, but instead, you should be picking the antibiotic that has the best data supporting a given bacteria within a given site of infection for a patient, and we don't really draw a huge distinction between static versus societal when selecting that Dr. Khyati Patel 39:06 antibiotic and the sulfa allergy on a patient chart nearly always means an allergy to a sulfa antibiotic, such as Bactrim. There are other non antibiotic sulfa containing medications that do not need to be necessarily avoided in this patients who have sulfa allergy. But do know that patients who have allergy to one medication, any medication, they're going to have probably a higher likelihood of allergic reaction to medications in other classes too. Dr. Sean Kane 39:38 So if you were surprised by one of our four medical myths today. Please take a look at our show notes at HelixTalk.com episode 135 where we have literature supporting the dispelling of these myths, and that's really the only way that we can finally get rid of some of these myths that have been propagated over years and decades, is by using literature. Again, if you have your own medical myth and you want to share it with us. Please send it over at HelixTalk on Twitter. We still love the five star reviews in iTunes, so keep those coming. So with that, I'm Dr. Kane, Dr. Khyati Patel 40:08 I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 40:12 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 - ? 40:23 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.