Pharmacogenomics: The Right Medicine for the Right Patient

Listen in as Dr. Mary Louder and Neda Leonard, MS, PharmD, BCPS, BCGD, explore the transformative impact of pharmacogenomics on personalized medicine, emphasizing the potential to tailor drug therapies to individuals based on their genetic makeup. From a discussion of ethical and efficacy concerns surrounding genetic testing, including potential biases and privacy concerns, to the importance of considering genetic factors that can either open the road for the body to use the medication or close that road off, they delve into many facets of this new field and how it can reduce the load of side effects and toxicity on patients and help them lead happier, healthier lives.

Learn more about Dr. Leonard's Pharmacogenomic services

Intro for "Since you put it that way" podcast.

Outro for "Since you put it that way" podcast

Transcript

0:20

Welcome all of our listeners to Since You Put It That Way, we've got an exciting episode, and first, we're live and in person. So this is Dr. Neda Leonard. She's a colleague of mine, and we are in beautiful sunny Colorado, which is where I used to practice--moved away, met Neda, came back for business. So here we are. So welcome. Well, thank you. Thank you for having me. You're welcome. I'm gonna give just a little introduction of what you do. Today's episode on Since You Put It That Way, which is the name of our podcast, is we're going to delve into the transformative world of pharmacogenomics and how it has a profound impact on personalized medicine through science. So, as we look at this innovative field, we're going to tailor drug therapies to individuals based upon their genetic makeup. And we're going to, not even potentially, we're going to revo--revolutionize patient care. So you're an expert in pharmacology, and you have a double boarding in geriatrics and what's the other one in? Pharmacotherapy. Pharmacotherapy. So, which means, rather than just being a pharmacist who, you know--well you, you describe it, I'm not going to describe. Okay. All right. So I am a dual board certified in pharmacotherapy and geriatric, which means it's extra qualification that board--allows us to do over many testing, and so forth, and continuing education, to be able to really focus on the pharmacotherapy, which is my favorite area that I have focused on the last 20 years. But then lately, 10 years ago, we were given the gift of the human genome being, again, mapped. And for that reason, we were allowing now the genetics to kind of infiltrates into the pharmacology world, and gives us that, that backbone for the genomics to determine what medication is going to be the best fit, rather than doing a one fit, you know, one size fit all, we're now going to prescribe in a way that is more precise. And so with that said, I'm also Mayo certified for this amazing science that we're going to be talking about today is pharmacogenomics. Yeah. So from my perspective, so I see you as a pharmacist who applies clinical principles to patients. Yes. So I am by, by training, I'm a clinical pharmacist. Yes. And I also a master's in pharmacotherapy and drug metabolism. So it's, it's got a lot. So you can be--you're safe to say I really, really enjoy drugs. But we did not do any--do any drugs before we do this episode, just to be sure. I tell my parents I said I am in the field of drugs, but I do everything legally. Yes, exactly. Exactly. Well, we're in Colorado, there's a lot of those that are legal, right? So yeah, and the thing that's neat about this is because as a physician, when I went through pharmacology, my goal was to memorize flashcards to pass the test to be on this. And then when I went into the hospital setting, and then went into residency and internship residency, you need to practice. You know, there's--say there's over 200 drugs, let's just say hypothetically, I'm not sure how many there are. But I use a handful over and over and over again. But thinking about that, the reason I do that is because I understood them. I understood how they worked. And I felt that those were some of the more safer medicines. But that doesn't mean that they were precise. That's, that's a very good point here. In a way, we are always given reference doses. We had--used to have this big old thick books that we opened up, we looked it up medication-- Used to read that book. Now they're kind of holding in the shelves on the shelves, and we haven't used it for a while. Now everything's on internet. But that doesn't mean that every all the information is really individualized or per-patient. So our goal, I always felt like, as a clinical pharmacology expert, that people came to me and asked me about how I dosed this. So there was a lot of elements, we always had the kidney function, we always had the liver function, the height, weight, so many elements of the patients that we always, throughout the year, traditionally we came across were individualized, individualizing those medications, but this was this big elephant in the room where we did all of those, and we did--weren't able to really have that same response from one patient to another. I remember going for example, in ICU bedding, one, one bed to another bed, same med, same dosing, same everything, one was in great shape. One was not in such a good shape, still saying there's no effect. The other bed was screaming of side effects. So we're kind of scratching our heads, saying there's this one element that is missing. And that was the precision that this pharmacogenomic is adding. Yeah, and I think that thing that's really important from that standpoint, as a physician, I'm an empath. As a person, I'm an empath. I'm that first. And then I happened to be a physician. And I was--always get beset when a patient would get blamed for medication not working. And it happened in situations where I had a, you know, a teenage student who wasn't taking their medicine for seizures, and--because she was having side effects from the medication. And they weren't stopping the seizures. So she was having both non eff--wasn't efficacious, and she didn't feel well. And nobody believed her. And so I chose to believe her. And the testing that I, I didn't have pharmacogenomics, and this was like, 18 years ago. But what I did was I went through by looking at the ingredients in the medication, and identified that one of the primary fillers in that medication was corn. And I looked in her history, and she had a documented allergy IgE, which is scratch test, and IgG, which is blood test, to corn. And she couldn't eat corn because she would get sick. And so in that situation, I felt pretty, you know, I thought it was amazing breakthrough to understand, you know, pharmacology from that standpoint. But that's a filler. That's not the active ingredient of the medicine. So in your world, how do you see the pharmacogenomics impacting the personalization of this? Mary, the--in our world, we come across so many toxins. We also have more access to our over the counter medications. And so now, it's not just the prescribed medications that the pharmacogenomics can help us with. It's also all of those over the counter, all the extra toxins that can come, fillers and more, that we can put, and most of my patients asked me, is this, that's going to only help me with my prescription meds? And that's not true. I've commonly prescribed over the--non-prescription over the counter medication, ibuprofen, naproxen, Aleve, Advil, those are all have genetic, curated and actionable genetic results, that I would, once somebody does go through the genetic testing, will bring that out to them. So this is a tool we give to the patient alone, without the provider even needing this information, although the providers do want to know if Advil works or not, but the patient just grabbing that over the counter, I can use that. We can also understand that, oh, yeah, I am a little bit over metabolizing caffeine, what I'm drinking right now. So they can understand how that--what that means. That means if somebody's, for example, a slow metabolizer, either 1A, 2G, then we can tell them that they are also metabolizing caffeine, I guess, food or drug, whatever drug of choice, right? And so it, for that reason it gives a more than just a prescription information. So in my in the world of pharmacogenomics, one size doesn't always fit all, as we have over, and people ask me, is this only me that is not responding to this medication? Or is everybody else experiencing this? And I want to really highlight this 99% of us have some sort of, I'd say variation in our genomics that that makes us not respond to the medications in general, in the way that they're intended to be used. So 99%. Now, that doesn't mean that they're all-- Let's reverse that. So, 1%, actually, the medications are working for, right? A lot of people will say, Well, what does that mean? Is it actionable? The actionable part is about--we're growing everyday, I get that new medication. 200-plus medication that currently have, maybe more 250, that FDA biomarker indication in their package insert, so this is no longer can be ignored. As perhaps maybe some of our viewers here know that there was an actual statewide complaint in Hawaii, very happy to hear about this. So this is very interesting. So in the state of State of Hawaii, had an actionable lawsuit against the manufacturer of Plavix, a commonly prescribed medication after a heart, heart attack or stroke. And that told them, I guess, that it was all about the population and safety. The population safety is that we have a gene, 2B6, that is, could be variable from patients to patients, we also have 2C19, and so forth. But one of the genes that are variable toward this specific medication makes it be ineffective, or makes it--makes, they will bleed more out of this, for this medication. So this, this, this was the concerning thing, because the population, the way that Hawaii says, is the--provides a little higher percentage of people with this biomarker. And so for people that were not--that this medication was not effective, and this, this little FDA biomarker that is in the--all package insert, was going unseen, unheard of, not really action, nobody was putting any action on that one. And so a lot of people were hurt there in that population. Well, let's--that's a super interesting point. Because if we back up and think about how we came to the conclusion, using drug testing, a couple things we have to touch on. One, a lot of the tests were supported by the companies that manufacture them. So there's a there's a bias, there's a conflict of interest even. And that just has to be listed. It's not that you can't do the test, it means you have to be aware. The second thing is when they choose the population. Honestly, most of the tests were done on white middle-aged men, because we now understand, and there's more discussions about different ethnic groups having, you know, different needs, and we're finding that from the human genome, we're finding that through even like our advanced childhood--or adverse childhood experiences, and social determinants of health. So we're finding that there. So this is another piece pulling in the genetics, and the variants based upon ethnicity, and just the variations within the ethnicities. And, and, you know, it's interesting, because when we look at the human human genome, we're 99.9%. alike as humans. So it's within that .1% of the differences even within the ethnicities. And right now there's Mayo is actually going, doing a tapestry project. We're having a project also in Colorado, that is happening, with really coming, putting a focus on what as population is our genetic differences, like she's been, like Mary's been mentioning, is really putting a highlight on what are our differences, that 1% difference makes a huge difference. It does. And then, you know, we go into the humanitarian part of being part of common humanity, where we're more alike than different. And yet, the things that make us unique, in this topic area, are things that could be life changing, life saving, or life threatening. So this is super important information that people need to have. So let's talk about--a little bit about some ethnic concerns, or not--ethical concerns about, and privacy concerns, because somebody's going to come in--the process is they come in, they get a consult from you, you take their history, their medication history, and then we do cheeky swab and send it off to the lab, there's DNA. So how ethically is that all of that handled? Because this is not 23 and me, or 23 and who are you, that's what I call it. So this is more, you know, stuff we're using that, as you mentioned, is actionable. So share a little bit about what you know of that. You bring up a good point. 23andme, it's a, it's a test of one gene, or maybe two genes that could be actionable. However, most of it is very nice. It's information about ancestry, it's information about maybe some cosmetic or as well as some information regarding for example, if you're not tolerating cilantro, so forth. But what we are after here is specifically, we're not even concern or care about any other testing genes that don't have actionable and cure--curated, meaning some backup with literature, what to do with this. So we want to get the information of what to do with the genes that give us information on the, for the pharmacology part. And with that said, there's a good point some people would wonder about, okay, what happens with that DNA? Well, the good news is that the DNA won't change. So the DNA, your DNA is yours for the rest of your life. Same way, that same coding, and also for us to a lot of our patients come back to us and come back to me sending me information about their new medications. I'm just newly getting started on--is this medication right for me? So the good thing is that we have the imprint, and we can put it against that and use it that way. Now, this, this imprint is not going to be used against anything else. By law, we actually have a law, that protects against genetic information for the consumers. So this is protected. This is completely HIPAA-compliant and would be not shared. Even with the providers--only we will share for the providers if them as a patient give us permission to do so. So it is very private information is only used to better the health and improve the overall prescribing. That takes that guessing out of it, out of the game. I think that's a real important thing, because we were talking earlier about the efficacy. If we go into medications for mood or depression, we have about a 33%, if we're standing up tall and minding our P's and Q's, as I say, efficacy, going into remission for patients. Meaning where they get better with medication--33%. And then I think, well, what if I was a heart surgeon and my success rate was 33%? I'm not sure people would come to me, and rightfully so with those percentages, right? But, but we seem to be able to accept that because it's mental health. And being able to literally use this test that shows us what medications going down what pathways in the liver, because this is where the action is occurring, and what medicines will work, what medications metabolize too fast, too slow, where the side effects are coming from, and then we can look at other parts of the pathways within the genes that support other components of the biotransformation or detoxification. And when we do that, we literally can have a precision--precisely analyzed way to give a medication. So it gives a lot of dementions, gives a lot of other--for example, before we--some of us could remember that before the MRI was available to us, that whole dimension was gone. So we would put our--you know, all of our information was on an x-ray, for example. But now we have something that is more precise, that can give us information about where we go with that image. If somebody's, like you mentioned, is a slow metabolizer on a medication pathway, we can perhaps even do more than just the genomic. From the pharmacology standpoint, we can declutter that pathway, we can go about putting the medication in a different timing. So if you think of it as a highway, and if that--we start decluttering that highway, that pathway that metabolizes that, that medication, we can get into the even higher usage, utilization of this testing, where we can say okay, now this pass--pathway is freed up and open for the medication to pass, to either get activated--because some of the medications, this is what the science gets a little bit more complex--some of these medications go through this pathway to activate such as the Plavix, the one that I brought up with a Hawaii, and at some of them go through the pathways to get, to eliminate it. So with that knowledge, and additionally, with a DNA knowledge and more, we can do so much more that we can't do without that. And so when this test is not available, sometimes in our clinical world, we look at it. And we just have a sigh because it's just just you have to go into the prescribing with some sort of a guessing and the guesswork happens out there, we have to then accept that we are--outcomes have side effects, have no effects, or trial and error on multiple--and this trial error in the world of mental health is really, it takes a big toll on the patient and on the provider as well, just because one med is given, six weeks later, for example, for antidepressants, six weeks later, you say oh, maybe this is not doing its job. And then we switch around. The switching is not very pleasant, and so it's it's on and on it goes. So that would be great if we can back up at the beginning, preemptively, ahead of time, say okay, we're going to do this the right way. Now, here's the question. It's kind of--it's a little pokey one, not at you, but at our profession in medicine. Have you met with resistance? Yes. Okay. I'm, I'm scratching my head, figuratively, here to think why someone would oppose this. Okay, so that's a very good question. So the the resistance comes actually from couple, couple sides. One, I've seen resistance from providers, just because it's time consuming to do this. And that's why I do my favorite thing is to partner with providers to provide this extra dimension to them, and to actually bring the all the translations to them in a Medication Action Plan, which I provide to them. And other resistant I see is that some of the providers and the patients come to me and say, we want the science to be perfect. It's a 10-year science, it's not perfect. Now my argument to that is that we didn't wait for MRI, for example, to be--give us the perfect imaging that it does give today. Today, the MRI that you see is much better than the MRI that was used years ago. So, it developed the science. And as it develops more and more is given. So to up for us, we say, okay, we know about 10% of the actual genomics here, and we're not going to use that because it's not 99%, then that ten percent is lost. So as as the size grows, and the utilization expands, we still need to appreciate both what it gives us and what the limitation it has. Well, I find that interesting that you want it to be 100% precise. What we've been prescribing for decades, is so much less precision. I mean, try, I mean, I'd reach--I'd be, I'd be double thumbs up, which is 50% better. You know, it, seriously, I don't have any ego on that one. I'd be like, if I can just, you know, instead of two out of ten, three out of 10, because that's the 30%, if I get to six out of 10, that is 100% improvement risk. And we did with, for example, in the example you brought up with surgery, it's the same thing, we just, we always may have complications, we still go for it. And as--the same way as we the medication. So it's better, but, it is very much like saying, Okay, I'm going to ignore the kidney function, we're going to ignore that, because it's not perfect. We don't know exactly what the kidney function is. But it's, it's that unknown. And it's the known that you have to apply, and it's that unknown that you have to-- You have to be comfortable with the unknown. Yes. And that's humanity. And, you know, I remember speaking at a conference a few years back about using genomics in my practice. And I would say I'm a very early adapter of genomics, and anybody who comes into my practice now gets a genomic test, because it gives me the blueprint to their overall health. Now, is it perfect? No. Are there more genes? And we know more about more genes? Yes. Because that's ever-evolving, evergreen, absolutely. But the information I have, for example, I can tell, should you keto? Should you not keto? Are you endurance? Do you need extra time to, to recover from exercise? You know, are you a rapid caffeine metabolizer. And it literally changes people's lives just with the imperfect, imperfect data that I have, looking at 100 and some genes. And you know, that's, that's way better than I was doing before, because I'd be like, well, I guess you could try keto, and let me know--Oh, your gallbladder kicked up? Oh, shoot, I guess now we have to image you. We have to do some testing. We have to draw labs. And now I go, Yeah, no, you're--you don't handle, you know, high amounts of fats really well. So keto is not good. Let's lean more towards Mediterranean with more lean meats. And oh, no, the reason you have the shoulder injury is because you need more recovery, and you're not a power athlete, you're actually an endurance athlete. So lower, you know, lower amounts of weight, but more repetition, and you're gonna need to hit the trail versus the, the, you know, high intensity, you know, throwing of, you know, kettlebells, and things like that. So it literally transforms how people are doing and living their life. But do you have a good patient example, a good case that--yeah. So first of all, I want to kind of give a little overall of the what in Precision Medication Center here in Colorado, the way we test is, it could be done anywhere, we're in Colorado, but we can go from East Coast to West Coast, sending the kit to the house with instruction and all the material to send it back. We do utilize the same laboratory as Mayo Clinic, because I'm Mayo Clinic trained, and so I wanted to make sure that that is done with the most comprehensive test. It's, I also enjoy their testing because the curated information comes to me all the time. And I'm trained on exactly what gene means in every every gene that comes to me so that I don't have this layer that I have to guess about because it is all there. And when this happens about seven to 10 days later than the patient's submits that very easy cheek swab, about seven to 10 days later, this big profile comes which then I put against a very--we have interview with a patient where we put it against their other medications, comorbidities, perhaps there has been things that have been tried before and it didn't work out. We give them side effects profile, we get a detailed information about all of that from the patient prior to that. And so then that way, that's where the work starts. Putting the patient, patient-centered approach to this test. And then together we can come up with something we call Medication Action Plan that could be shared with all of the providers, mental health, cardiologists, oncologist or family practitioners as well as with the patient and the family because I think we're the biggest advocate that we have is really for us to empower the patient. Let them know about the information. Yes. So the consult then happens that way. So with that said, I want to give you an example of just a recent example that really, really worked well. We had a teenager, mom brought, or nurse practitioner to refer to us, mom brought teenager here, the teenager was--said, I'm not taking this med. This med is giving me--the brand new med that was started for OCD--anxiety, OCD, and many more mental health issues--but it, this is giving me dry mouth, giving me drowsiness and falling asleep during the class, I'm just not getting through the day that I just don't, I will not take this. So mom was here actually, for us to convince the teenager to take the meds like because that's the med that was prescribed and mom was very compliant. Teenager wasn't. So what we figured out, it's really interesting, because the test comes and I'm looking at the test, the first thing I see is that the metabolism of that specific metabolism for medication, OCD medication, was completely defective, meaning both mom and dad gave two different alleles to this teenager that is not functioning. So pretty much the patient was taking it-- The road was closed. The road was completely closed, and nothing was happening. And, and, he was very consistent with this, because he was saying, I'm getting all these side effects. And I could see that because there was no clearance of this medication from his body. So it was just keeping every dose he was taking--and I was glad that he stopped taking it, because every dose was kind of added to that bucket more and more in the side effects. And so, with that said, we were equipped to tell the provider that hey, this is time to stop this medication, this is the way you can stop it because a lot of times medications are--to be stopped, they have to be in a very certain systematic way, so the patient-- Safely. Safely. And so that was stopped. And then we also were precisely put the medication against, or the new medication, the SSRIs that we picked against, again, the genomic of this patient. And so to make sure that that is precisely done in a no more trial-and-error way. And that was a big success. Because in this patient's case, we couldn't have been wrong, because we had to be very precise, because here's a patient with a lot of mental health, suicidal ideation and so forth, and we couldn't miss. We have to be completely accurate and precise. Yeah, and I think that that, the key points in that are, from a physician, and from how I practice medicine is, they weren't listening to the patient. If you listen to the patient, they'll tell you what's wrong with them. The patient was telling you--not you, but everybody, you were third in line there, you know, the prescriber, the mom, and then you, that the medication was the wrong medicine. And so, it--and we, in this situation, we didn't listen to him. And then we made the patient out to be bad, because the patient wasn't doing what he was supposed to do. So we label those patients, as a physician, we call them non-compliant. Well, you know, I'm just trying to figure out how many blocks we have to stack up against folks, so to, you know, prohibit or prevent their healing. And this is the part where I think it's so important, because the precision comes in through the science. As precise as it is, and is going to get more precise, because we'll know more of the human genome, but this is lightyears ahead of what we were doing even a few years ago. And this is lightyears ahead in terms of how a person could be healed. And I mean, and I actually mean healing because we can bring in the emotional component. The trauma from going through the medical system, of not being listened to. And there, if they have a tendency, a patient has, with OCD and anxiety, suicidal tendencies, they may say this is too much and they leave the planet. And this is how serious this is. And, and I think that this is super important for us to understand, as physicians super important for just understand in prescribing, but more important for us to understand in the hum--humanitarian approach to medical care. I just wanted to highlight other areas that pharmacogenomics can help. I know we spoke about mental health and it's a big, big issue, as COVID especially, but other areas that we are really utilizing this science is amazing. Science is in--cardiology, we do have, for example, a lot patients that come to us that are wanting to no longer test, be a test patient on a statin selection. They have, they have a lot of muscle pain, and they say, you know, we want to precisely see what--and besides, statins do save lives in a prevention of the stroke and heart attack. So we're more than happy, we're honored to be able to give him a selection on what, which one of the statin gives them less side effects. And, and they can continue with, with taking those medications, we also have a lot of polypharmacy, where people are on a lot of medications that come to us just because as the complexity of medication list gets bigger, then more and more of these biomarkers get into action. And you mentioned you had a patient who was on 14 or 15 medicines. You can, you can geek out on this. Yes, we had a patient on 14 or 15 medic--medications and, and we had a lot of collateral finding, Mary, that we do have actually. I get excited--to get excited. But with the polypharmacy-- Yes, because you see a lot more, you just, you have this great imprint. And you can put it against all of these medications, and there are many of them on board. And with this specific patient I, I was able to optimize, for example, the proton pump inhibitor for her GERD, and I was able to-- The little purple pill folks, that's Prilosec. All of those do get over the counters now, there are many of them over the counter. And I was also able to come to tell her And people may think one of the important pieces of this is, oh, by the way, your cholesterol meds that are giving you a side effects, it can be doing this way and and using this other one that will be the same intensity for cholesterol medication, and often patients resist medication because of the side effects. you can have less side effects. She was happy about that. And Now, this could be side effects that are real, but they're more also we were able to--she was on for medications for, for blood often, and I'll call out the patients on this since I'm a pressure. And that's usually when you see the pharmacogenomic in action when when we put three or four medications on board because it's like resistant hypertension. But in my opinion, the first med was not optimized, because we didn't know about the genomics. The second med comes on board, the third and fourth comes on board. Hopefully that doesn't come on board. But we were able to put her down into two medications, but with optimized dosing that pharmacogenomic would give us and, and be able to decrease the pill burden on her. prescriber, the side effects they read. And so that is That's true. strongly the power of suggestion--doesn't mean because And so I think understanding, you know, the possibility of it's written or we know from his study, that those side effects could occur, that you're actually going to have those side effects. And, and so there's no, and it becomes then a tug of war with the patient. And the doctor-patient relationship, I see it as a sacred interaction of communication, trust, and mutual respect. So that goes out the window when we're fighting over what we think side effects could or couldn't be. potential side effects, and are they actually real? And then I think one of the other things too, is there's other testing that goes into, or that that butts up against the pharmacogenomics. For example, I use an advanced cardio--cardiovascular test through a lab that shows me if the patient either manufactures cholesterol or absorbs cholesterol. And that can be a game changer from using a statin to block the production cluster on the liver, or using a medication that blocks the absorption of cholesterol from the foods we eat. So I have patients who have been on heart healthy diets, according to the American Heart Association, and their cholesterol won't budge with a statin. And they sometimes because we increase, what do we do? We increase the dose of 10 milligrams doesn't work, we'll go to 20, we'll go to 40. Well, what Dr. Leonard is saying over here is, the dose change might not be the reason that the medicine isn't working, or too low of a dose, it's just that it's not the right medicine. And so when we push the medication up in a higher dose, that the patient literally can't utilize in their body, we will give you side effects, guaranteed. And that becomes then a negative, what would be considered a negative feedback loop, when your body's like, well I'm not trying that other thing, I'm not trying that. And with the side effects of a statin, if we, you know, are a little, you know, picking at that a little bit, poking at that a little bit. It's the muscle cramps, it's the fatigue. Well, I wonder about, too, just some brain function in the elderly, and I've seen that a lot. And then when I've taken people off statins who've been in the nursing home situation, they--or not situation, nursing home living, they like wake up. And they're like, alert. And they're like, what happened? And I go, I just took their statin away from home because at 93, you know, if they, you know, departed or left because they had a heart attack or stroke, that's probably okay at 93. And so I always stopped statins at a certain age anyway. But in this situation, and there's many reasons too, which we, I think, you know, we should come back and do another podcast on how our body biotransforms medicines, or detoxifies or metabolizes because that's also the work that I do to help the body recover from the medications that have been taken, in addition to toxins. So, I think we've got enough here to keep going for a number of episodes on this because this is such an intriguing topic. And this is a topic that is so perfect for this podcast, because, you know, I want to say to our listeners, no, I can't see you. But I do see you figuratively, I do understand you. And the patients that get dismissed from practices or marginalized are often the patients that find me because no one will listen to them. And so teaming up and collaborating with the Colorado Precision Medication Center is what I've chosen to do because I want my patients to have the very best with the pharmacogenomic approach as well as the integrative holistic approach for their medication care and treatment, detoxification, and really, to have the best results possible that we can guide. Yeah. We, I agree. I think this is, there's just so much to be, to be done, that this is the multiple approaches can really enhance health. Yeah. So I thank you, listeners today, for, for hanging in with us--a little bit of a technical conversation at some parts, but very, very good. Stay tuned, we will soon to have part two where we're going to go into really what happens with certain medications and we'll--we might even pick out a few that while we think overall they're doing good we can, you know, know how to use--utilize them better. So thank you, Dr. Leonard, for being my guest today and I look forward to having you back with us. Thank you. All right. Bye from here, on Since You Put It That Way.