Chronic Pain: Modern Approaches to Management *ACPE-Accredited*

[Music] Hello everybody, welcome back to another episode of the Core Consult Rx Podcast. Join me as always, Cole Swanson, what's up man? Nothing much, live in the dream, much you Mike. I hear you, not too bad. Right, literally, I was walking up the stairs to jump on and start recording, and my son started yelling "Dada" from his room. Oh boy. So hopefully he will stay asleep at this time and we can get through this whole thing. We'll say. Or if you hear him screaming in the background, that'll be nice background noise. Screaming good. Yeah, yeah. That's what editing is for. Are you one of those? Do the screaming kids just like, does it bother you? Can you not, like, does it, like, does that like nails on a chalkboard? No, I can, I mean, if they're just like, whiny and like, you know, they're getting tired, like, in the ear, something that are just whining and stuff, then I can totally tune that out, like, pretty easily. If they're like, obviously, I always had a hard time, like, at bed to like, if he wakes up and he like, is like, you can tell, he's like scared or whatever. That's where I'm always like, they're like, just let him cry. I'm like, nah. Nah. Nah, I think I'll go get him. I know. I thought it would bother me more, but like, if it's just crazy and they're screaming downstairs, it's like, it does not bother me at all. I don't even, I can pretend it's not even there. And then Anna's like, it ends up working. Yeah. You're gonna do something. I'm like, whoa, yeah, I guess they're screaming. I don't know. I just all of my own head. Yeah, I don't know. They do that all night. The other night, we have a cat and it likes to come in when my oldest goes to bed and while he's being read his stories, it kind of sits on his bed and stuff. So usually we shoot out afterwards, but I guess we forgot to. And I was downstairs watching TV and I hear him just screaming bloody murder. Dad, dad, screaming. And I thought he had a night tear, so like, I ran up there. And it turns out that the cat was under his bed and started scratching on the bed. So he just obviously thought there's monsters under the bed was the first thing he'd lost. If I heard that, I'd be like, oh, well, completely great monsters are real. For the only one he realized was the cat. He calmed down after a couple of minutes, but it was just like the most terrified. I feel so bad. I've never heard such terrified screams. Oh yeah. That sucks. That's so bad. That's the worst. So that's the kind of stuff that I used to not, I mean, like before I kids was just like, whatever, do you be, make a, you know, lock a menu and catch me. Take a fight. I'm out. Make a man. Oh yeah. That's, I have zero left. You're after actually having a year and a certain kid. You're toe push over. Oh yeah. I'm like, I'll kill that cat for a scare. You would you ever scare me? People are going to, yeah. It was awesome. Like, do not kill cats. Oh yeah, that's good. I should be out. That's his disclaimer. That was a joke. I don't even have a cat. So I can, there's what's apparently good. Yeah, that's, yeah, we'll go ahead and get that out of the way. So nobody has to send us any mean comments. That was a joke. But speaking of, I guess, being uncomfortable, not just necessarily with fear, but we're going to be talking about pain tonight and talking about some of the ways to manage pain. Both, you know, acutely and chronically and obviously we're somewhat limited on, you know, medication options as far as different classes. Most of the chronic pain management stuff kind of revolves around the opioid class and, you know, some of the other augmentation options and things depending on, you know, whether it's neuropathic and whatnot. But we also have a new drug that we'll talk about. I guess I don't even know if new is the right where it's what came out in January now. So almost seven months old. So, but I don't think we've talked about it at all. So we'll talk about that as well. And this is going to be an accredited episode. So for those of you who are free C members and get your continuing education through that platform, make sure that you listen carefully. We will give you a password at some point during this episode that you will use to access the post activity test on free C's website for this episode. Past your 10 question multiple choice tests and you will get your one hour of continuing education credit for pharmacists and nurses. And I believe, I know I'm sure it changes state-to-state, but in South Carolina we have to have one hour dealing with, is it just controls or is it opioid like pigment, or is it specifically whatever they're used for? Specifically, yeah. Okay. So for those of you who live in South Carolina and I'm sure other states have other, you know, are similar. I think it's, I think it's just control, control substances. So I take that back. I think I always end up doing something around opioids. That's why I said that I was even questioning it, but yeah, so we can check either way. You can check that box with this. So we will go through, you know, some of these different meds and talk about all this, but make sure that if you're not a member of free C already and you want to start accumulating for this, your continuing education credit bank, make sure that, you know, check them out and see, you look at, you know, assess whether that would be a good fit for you, but I'm sure you could find, if not many things, at least something on their platform that is beneficial and worth your while. And if you're listening to our podcast, anyway, you might as well get credit for it. So definitely encourage you to check their website out. They have a lot of great material on there. And, you know, thanks to them as always for continuing to partner with us. They've been fantastic. So we will always be advocates for them, you know, just we've built a long relationship at this point. So check them out if you can. And I guess to get things started, we'll just talk through some background information. You know, and then we'll we'll jump into the meds. But as far as, you know, the classifications of pain, you know, you really acute and chronic or too big, obviously subcategories, acute pain being, you know, just a short duration that is resulting from, you know, post surgery, it could be an acute illness. The patient could have had experience some kind of trauma, could be, you know, labor induced and whatever. But it's not something that is going to be a long term thing. The patient, obviously, may need some kind of pain control for a short period of time. But then the, you know, the body recovers, the pain goes away. And patient can kind of give back to normal with chronic pain. Yeah, the pain is ongoing and recurrent. And typically, you know, we're thinking patients have been in pain for, you know, at least three months six months or so. And not just the fact that they're in pain. But also the fact that the pain is affecting the patient in a, you know, negative way. Chronic pain doesn't always actually stem from a identifiable ideology. And especially when we start talking about like fibromyalgia and things like that sometimes you like can't find a definitive origin of the pain. But it can be extremely debilitating and horrible for a patient's quality of life. And also extremely difficult to manage in some cases too. Because it's not like we have medications that take the pain away with zero, you know, issues as far side effects or long-term problems and things. So pain is probably one of those, on the surface seems to be not as an intense specialty, if you will. But one that I do have a lot of respect for, because it would be tough to do that, you know, on a full-time basis and be primarily in pain management. I feel like just because, you know, there's just so many other things you have to think about on top of, you know, just the medication side of things. But, you know, we also have patients obviously dealing with things like cancer pain and, you know, that's obviously a more chronic situation as well. But it can also be more chronic anacute depending on whether they're at in treatment and, you know, how they're responding to treatment from the cancer and, you know, all that kind of stuff. And, you know, it can be kind of a different ball game altogether than just regular chronic pain, obviously, with cancer, these patients have a life-threatening condition and, you know, it can be even more difficult to manage their pain because of how intense it can be. When we're talking about an acute situation, we're really just trying to relieve the pain, you know, but we're not as worried in those cases about tolerance, you know, developing or dependence, any kind of like psychological component, not to say that even short durations of things like opioids can't cause problems because they definitely can, but, you know, we're more so just trying to keep the patient comfortable and hopefully get them back to their baseline so that they can kind of go on their way. You know, we're not having to necessarily think about all the psychological issues and long-term problems that can come up with pain management. Obviously with chronic pain, all of that needs to take come into account. I'm not just a patient's relief of pain, but they're mental well-being, their quality of life, they're sleep habits, behavioral health, all kinds of stuff. So that can definitely be a lot more difficult to sort of manage. And then you wanna talk about some of the more nuanced classifications of types of pain. - Yeah, and these are really tough ones because it's pain that isn't always associated with something like a clear thing, like they have a degenerative dysdysseser issues with their back or cancer or something like that or a direct insult with acute pain. They can have maladaptive pain, where it becomes disengaged from a noxious stimuli or even the ability to heal. It can result, it can be a result of damage or abnormal functioning of the peripheral nervous system and or the central nervous system. There's also neuropathic pain that we hear about a lot. You can have a peripheral nerve injury like post-repetic neuropathic or patients who have diabetes who have diabetic neuropathy. You can also have a injury to the CNS, like a steam stroke or a more progressive situation like multiple sclerosis. Maladaptive pain may also be centralized, where there's no nerve injury or inflammation. You can have neural plasticity where pain circuits kind of rewire themselves, both anatomically and biochemically. Missmatch between, you can have a mismatch between pain stimulation and inhibition. That leads to an increase in the discharge of dorsal horn neurons. There can be episodic or continuous pain transmission, exaggerated painful responses to normal noxious stimuli. So they might have hyperalgesia or a painful response to non-nonti-nonti-stimulai, like aledinia. - Yeah, I think the hyperalgesia is one of the things that doesn't get talked about enough when it comes to long-term opioid use, for example, and how that can start to occur where all of a sudden your response to pain is more intense than it would have been, prior to being on chronic medication and things. I feel like that's just something, at least, to my experience that doesn't get brought up enough with, amongst talking to patients and other clinicians and things, 'cause I feel like that, it's an important factor that patients need to be aware of as well. - And those central pain disorders are where a lot of the kind of non-opioid medications pop up the TCA's, the GABA pins, and they're good, and SNRIs and stuff like that. They can certainly be beneficial there. - Yeah. When we're talking about just acute pain management, obviously if we can use non-opioid, even non-pharmacologic therapies, that would be ideal. Non-pharmacologic being things like physical therapy, in fact, physical therapy for a lot of different conditions that result in the patient going to pain management, physical therapy can be great for a lot of things. That's another thing that I feel like, even when doing an annual wellness visit, there's something I've talked to patients that are on chronic pain meds, or trying to get chronic pain meds, and I'll ask them about physical therapy, and they're like, nah, I don't know. They just either don't see the value or maybe they didn't have a good experience in the past, but physical therapy can be huge, especially if you find a good physical therapist that's a good fit for the patient. I think that can should never be overlooked. That is a very useful tool that a lot of patients should be encouraged to do. I can't say personally, I get as excited about things like chiropractor in general. I know there's some great ones out there, but the manipulation and things like that, as far as the joints, not psychological manipulation. But not yet, I'm trying to throw that much shade, but there's different schools of thought on whether that can be beneficial or not, as far as sending it to a chiropractor. But also, if they have access to any kind of, whether it's a personal trainer, or even just a gym membership or things like that, formal exercise programs can be really good. Weight loss is always something that should be encouraged, especially when we're talking about osteoarthritis and whatnot, diet changes may even be a factor as well. And so definitely lots of non-pharmacologic approaches that we should encourage patients to at least consider. And then even some more complementary or integrative approaches as well, like some patients will find relief or at least benefit from acupuncture, things like Tai Chi, Yoga, and then more on the mental side of things, like things like meditation, mindfulness, different types of relaxation techniques, lots of options out there that we should at least be encouraging patients to look into, if not directly recommending any of those things in particular. But it doesn't always have to be straight to medications and just like most disease states, doesn't have to be straight to medication and that's just the end of it. There's a lot of non-pharmacologic approaches that we can consider. Have you seen those videos making fun of the caropractor videos where they got somebody in position and then they're like being really calm and quiet and then cracked the heck out of the head. The guys like they're doing that and they've got their corridor open and they're like just relax. It should be a little bit. (laughing) - Just like the corridor class. - That's great. - Yeah, that was pretty great. Speaking of video, whatever that video you were trying to explain to me that Instagram read, we were talking about for like five minutes. It literally the next day popped up in my, I was just doing scrolling on Instagram before bed and I was like, oh, there it is. This is definitely the one you were talking about. - That's the way it works. - We probably didn't even have to talk about it. I probably could have telepathically just relate it to you and your phone would have popped it up because that's the way it works. - And we're just, it's crazy. - It's the metaverse dude. - We're all in it. - I still have an Alexa. It advertised to me the other day. Oh yeah, I'm sitting there. My kitchen, 'cause you know, it's a glorified kitchen timer. And I guess it can hear me talking to my wife and it just starts talking unprompted and it's basically advertising the new Superman movie and asking if I want it to act like Superman. And I'm like, did Alexa just advertise to me? I've never had that happen before. - And then just ask me if I wanted to be Superman. I'm an adult man. Why would you ask me that? - It could run right into the case. - Instead of using Alexa's voice, it can be like Superman's voice or whatever. And it was obviously a partnership with the new Superman movie and I'm like, - Gotcha. - I thought I was asking you if you wanted to be something, is it like, it was like, hey, you should, I know you're an adult, but you should put on a cape and run. - So it got me thinking of this new, have you seen these new like house hold robot things that are out there and help with dishes and putting things away, putting with groceries and stuff like that? They're not in, - Not like, I've seen things like the words, like stationary, I can't believe, but like I need a logical robot. It's walking around and doing stuff. - Yeah, you need to look at these things. I'll have to find the company again, but there's this one American company who has like made ridiculous strides with their most recent model. And it's kind of like nuts to look at. But it got me thinking about if we had one of the, like they just predicted like 10 years, everybody's just gonna have one of these things in their home like the Jetsons. And it got me thinking like, what if my household dish cleaning robot just started like advertising to me and you know telling me about the upcoming Super Bowl or something like that, you know? That would not be okay. - Or just decided it wanted to take over the house and wouldn't it probably be? - You no longer live there. - What it would probably be is like you have to, just like a Peloton, you'll have to buy the robot and then you'll have to buy this ridiculous like pay the subscription fee every month. But if you accept your robot with ads then your subscription fee gets cut and half and then your robot will randomly just come up. You'll be sleeping. I'll just come up to you right up here. - It's a pay. - Wait, you're like, have you tried to retove? - They have a new flavor. - I reckon I saw it. - It'd be great. - Yeah, that would, I mean a robot would be cool but I do have, I'd be a little suspicious of it. I'd keep on. - Oh yeah, I would trust it with kids. - Casey tries to attack. I've seen a robot a few, - I would wait some time. - I'm sorry for that tangent. We certainly need to move on. - No, no, sorry. - Or opioid stuff. So like Mike said, we want to exhaust any non-pharmacologic and non-opioid options that we have. And I think people are trying to do that more, especially before moving on to chronic opioid use. If opioids are needed, and we'll talk about some situations and what drugs you would use in other situations, but in terms of opioids, the CDC does have some guidelines for prescribing them. And you know, the CDC is always gonna recommend trying to be pretty judicious with your opioid prescribing. They want, they recommend establishing clear treatment goals and like Mike kind of touched on earlier with the differences between acute and chronic pain. With acute pain, we want to get rid of the pain completely for the short period of time that they're gonna be using this opioid. With chronic pain, we recognize that that's likely not possible. And if we were to do that, it might be dangerous for them in other ways. So the goal is more functionality and allowing them to live an undormall life and participate and do their activities of daily living instead of being completely hampered by their pain. So steady. those expectations upfront with a patient is certainly important. Discussing the known risks and what benefit they could have before you start them, the patient should be fully aware. They, the CDC prefers immediate release opioids over the long-acting formulations like the controlled release, long-acting other ones. Always use the lowest effective dose possible in the case of, lowest effective dose, but also the shortest duration. So they say in the case of acute pain, three days should be sufficient. They say that more than seven days is rarely required for an acute pain situation. They recommend the monitoring of the PDMP programs, the prescription drug monitoring. When you initiate and then periodically after that, they also recommend you're in drug screening prior to initiating opioid therapy and then periodically. So that presumably to identify if they're getting opioids from an outside source or if they're I guess using illicit medications that just it puts them in a category that's a higher risk for abuse and overdose. I had a patient that I just saw like a few weeks ago and we was an annual wellness visit that I was seeing and she's on chronic pain medication. I wanted to think it was tram but it was saying how it didn't really make it feel that great and she's like I do need it sometimes. I wish I didn't have to take it every day. And I was like well if you don't take it for a day when you were pain like I'm going to mail back really severely and she's like no not necessarily. I'm like well then why do you take it every day? I was like well because the pain management doctor I go to drug test me when I go in like once every three months or whatever and said that if the medication is not in my system that they won't prescribe it anymore and she's like and so I just go ahead and take it every day so that it's in my system and so that you know I don't because I can still at least have access to it for the times that I do need it and I'm like I'll say but you know that it's in your system after just that dose right? You don't have to take it every single day for it to still be in your system for like you know when your appointment is I was like I they're doing that so to make sure that you're not like getting you know giving it to someone that shouldn't have it and you come in for your appointment is not in your system and lots of words that all the medication and she was like are you see like didn't yeah it was that's interesting. At first time that's ever like she's like literally was like like taking this on a daily basis. I can see where she could if it wasn't explained or I could certainly see where she would be confused by that. And she's like wait so she's like I thought like you have to get a consistent basis for it to actually show up in your sound like oh now you take one dose it's going to be in your system. You know usually it's the other way around that people are worried about right? She's trying she's trying to make sure it's in her system. Yeah that is yeah that's it was funny it was just the first time I've ever had that combo so I thought that was interesting. You know what you obviously we have different medication options besides opioids you know we'll spend the majority of time kind of going through opioids when we're talking about things like acute pain and chronic for that matter. You know it can be into it can be Tylenol if it's more mild or moderate opioids obviously usually are saved for the severe pain and then you know when you start talking about chronic conditions you know visceral pain neuropathic there are definitely some other options. People mentioned you know things like tricyclic cantered presence SSRIs, SSRIs, deloxetine is one that is often used for neuropathic pain such as diabetic neuropathy, lidocaine and all of its various formulations is another option there. Aclyphin and some of these type of meds but when you get into functional and inflammatory conditions that are causing chronic pain you still may see NSAIDs and what not being used you have to still be cautious about long-term side effects of those as well but opioids tend to be sort of still the central kind of thing that we think about when we're talking about long-term chronic pain especially if it's severe enough but that being said we do have a new drug that has been approved this year like I said earlier back in January of 2025 we saw a drug get FDA approved, a joint of X which is the first in class medication and it's kind of coming at pain from a totally different route and generic name or chemical name is Susan Triginine. I may be pronouncing that way wrong but it is a drug that has been in the pipeline for a while but finally actually got all the way through the FDA approval process. From a mechanism of action standpoint it is working on something called the sodium V1.8 sodium channel and involved with no deception and so to give you a quick rundown of this the drug's target like I said is voltage gated sodium channel so sodium V1.8 and it's a genetically and pharmacologically validated target for pain management especially at this point out of this drug is FDA approved and it does play sort of a critical role in the transmission of pain signals. It is the expression of that channel and the gene that codes for it is found almost exclusively on the peripheral pain sensing neurons so the no seceptors and that includes those in the dorsal root ganglia. The neurons are responsible for detecting noxious stimuli so injury inflammation things and they generate those electrical signals and action potential that travel to the central nervous system where they are perceived as pain. Those types of sodium channels are not expressed in the human brain. They are not in the spinal cord or cardiac tissue and so the selective peripheral expression is kind of a new cornerstone if you will for this new targeted mechanism and also results in a much more favorable safety profile and acting only on channels in the peripheral nervous system it can definitely modulate pain signals at their source without interfering with the complex and the neural functions of the central nervous system or any of the electrical conduction system at the heart or anything like that. Obviously this is a very stark contrast compared to opioids which they exert their primary effects on receptors within the brain and leads to a cascade of central affecting you know things euphoria, sedation, respiratory depression all these things that can be potentially problematic down the road. So, you know as far as the drug itself it was there's a few different studies they got to prove that the navigate one and navigate two trials. The navigate one or actually both navigate trials they had an active comparator arm which was hydrocodone and acetaminophen and that was those that 5 milligrams per slash 325 and given every 6 hours and the patients could also use a rescue medication and either arm whether the active drug or the active comparator they could also use rescue medication of IV profen 400 every 6 if they needed it. And the primary point they were looking for was you know the pain intensity difference from baseline over 48 hours and that's sort of standard endpoint in acute pain trials and at the end of the study both in the different types of surgeries that patients that had that you know were kind of the inclusion part of the inclusion criteria. The sousitrogen achieved its primary endpoint showed statistically significant and clinically meaningful reduction in pain compared to placebo and it was basically about the same as the hydrocodone. The other thing that was the side effect profile was definitely favorable for this new drug. Patients had a lot less instances of GI issues nausea, vomiting, constipation and really the main side effects from the sousitrogen that were reported paritis, some muscle spasm, skin rash and then asymptomatic increases in serum, creatinine, phosphokine ACE levels. But from an overall GI standpoint all that that you know we oftentimes think about with opioids it wasn't a much better tolerated drug. And thinking along the lines of long term use which it's not currently approved for long term use but thinking you know if it does go that route it doesn't seem to have the same you know sort of abuse. potential is an opioid would and definitely seems to have a much better safety profile long term as well. We talk about things like respiratory depression and whatnot. As of right now, it's FDA approved for acute situations post-op or what have you and really hasn't been studied past like the 14-day mark. My guess is that it eventually will get FDA approved for more chronic treatment but as of right now it's should only be used in the short term and I imagine even if you wanted to use off-label for long term getting it covered by insurance to longer than 14 days would be almost impossible if not impossible. If any of you all out there using this drug and have had luck with it let us know though because if it is something that insurance companies will pay for it would be interesting but as of right now it's just approved for short term use and one of those things that I'm hopeful you know will be a game changer down the road. I know two of my PA students that are working in pain management now that like my former students they've graduated now but two of them have already reached out to me over the last couple months and said they have started using this in a few of their post-op patients. So yeah I'm looking forward to getting some real-world feedback because like I said I don't work in pain management myself so it'll be interesting but definitely check out this drug. There's a really good med scape look kind of like summary article that runs through the navigate studies and just kind of the run down of like potential drug drug interactions things like that you know just to kind of give you an overview but check that out and again brand name is Jornobax. Yeah I'm interested to see what that goes. Yeah so we'll spend the rest of the time primarily talking about opioids so we'll pop back into those just to give you an idea kind of wrapping up what we had talked about before one guideline for the management of low back pain which is a very common cause of chronic pain is to start with non-pharmacologic therapy moving on to insets his first line they would say tram it all a second line and then saving opioids for the last line after everything else has failed so just to give a little background about opioids just some general information that we're mostly familiar with but there are there were naturally occurring opiets which were used for a long time until the 80s which is a group of compounds derived from the opium poppy but then opioids were discovered or created in the mid 1970s which include all synthetic and semi synthetic drugs that mimic the actions of opiets. There's also the term narcotic which references groups of drugs with actions that mimic those morphine narcotics can cause the classic triad of symptoms or signs like respiratory depression pinpoint pupils and increased mental status. Yes not to be confused with any controlled substance like I often times hear people reverse. Yes. Noorcaotic is an narcotic I'm like that that's an narcotic is not an any. Especially any scheduled two people would just say that term narcotic. Yeah similar to morphine but to kind of give some of the breakdown based on you know the different meds that are out there or different opioids are out there some of the natural opioid agonist that are still in the market morphine obviously and then things like coding and even like cold mentioned old school opium. Some of the semi synthetic opioids would be like hydrocodone or hydromorphone oxymorphone oxycodone even like heroin and then we have our full like synthetic opioids which are completely produced by lab synthesis so things like methadone fentanyl but parodine and then we also have like our mixed agonist antagonist which the main one that we use nowadays is the buprenorphine and then sometimes you may see some patients on like butorphinol or something like that but buprenorphin is by far the one you more readily see and then we also have our opioid antagonists which obviously can be you know used in the case of an overdose or as an abuse deterrent so like naloxone and different available formulations and brands that are out there for naloxone that can be used in the case of an accidental overdose and then naltrexone is another opioid antagonist that is oftentimes you know either used in conjunction with is like an abuse deterrent or something like that but naloxone whether it be a nasal spray or you know whatever route it's being administered is very commonly used med to prescribe along with opioids to make sure that patients are staying safe and if they were to accidentally have an overdose then you know they're hopefully a friend or family member can administer naloxone and get them but pull them out of that respiratory depression. So of course how do these work they bind to opioid receptors in the CNS which causes inhibition of the ascending pathway it alters the patient's perception of pain. We mentioned some of the big scary adverse effects like respiratory depression, CNS depression but they also cause constipation especially when used chronically so that's something that should be addressed with patients ahead of time and sometimes there's preemptive medications recommended or prescribed. As far as dosing it depends on what your goals are and what is being treated but also if the patient is opioid naive versus if they're opioid tolerant you may need to adjust the dose. There's considerations when converting between different opioids and also different formulations like immediate release and extended releases and discontinuation especially when used chronically really shouldn't happen abruptly. You want to decrease the dose by 25 to 50% over two to four days at least that's one recommendation. And then you know ongoing monitoring if you are going to put a patient on opioid especially long term you know patients need to be evaluated within one to four weeks when it first being initiated on treatment they also need to have a quick close follow up if there's any type of a dose increase throughout their treatment and then making sure that you're evaluating the benefits and risks every you know one to three months or even more frequently if the patient's at a higher risk of an overdose or has a history of opioid use disorder that you know they're trying to to work through that you know when we think of things like an overdose you know oftentimes you know your brain just goes to the thought of a patient just took too much of their medication or took a response which something like that but there is a lot of other factors that can put a patient at risk for having an accidental overdose other disease states you know does the patient have any kind of pulmonary issues like COPD obstructive sleep apnea things like that can put them in much higher risk for you know experiencing that respiratory depression and you know it results from an overdose and then other medications that they're taking along with it certain types of muscle relaxers especially soma, carosypardol it can be a real concern if taken with opioids, bends it to azapines you know a prasolam, clenazapam things like that can definitely put a higher a patient at higher risk for an overdose alcohol consumption and then other factors you know the patients being elderly you know do they have some kind of hepatic or renal insufficiency but there's other factors that need to be evaluated and monitored long term if the patient is going to be on chronic opioid therapy before we get rolling because I think we're already past halfway more so let's do the password real quick before we forget to do so the password to use on frece.com's platform in order to get the post activity test is pain 25 so pa i n all capital letters and then the number 25 nice and that will give you your 10 question multiple choice tests, crush that and get your one hour of cd credit for all your pre-c members out there. Easy peasy lemon easy. All right yeah let's pop through some of these medications starting with the natural opioid agonists like morphine comes in a variety of dosage forms liquid, I am IV PR, rectically intrathecal, IR and ER formulations various brand names been around for a long time used a lot you may not see it used as much for chronic pain it's like hydrocodone and oxycodone but still very much used and then used in the hospital for various other reasons it's cheap. It does have renal adjustments it's recommended to avoid it in patients whose chronic illness less than 30 also of note it inhibits the release of ganatotropin releasing hormone from the hypothalamus which can lead to decreased testosterone and cortisol. This would be called opioid induced hypogonetism. So male patients may present with symptoms of erectile dysfunction in this case, decreased libido, and decreased analgesic efficacy. Women can experience alopecia, amenorrhea, depressed mood, as well as decreased analgesic efficacy. And a drug that we don't see nearly as often in more coding. So coding is a pro drug of morphine. And it's been around for quite a while. They do have a standalone coding product, which is a scheduled to medication. Although more commonly you'll see coding in combination with the CETA-Medifen. So things like Tylenol number three. And then there's also different combos with anohistamines and different anti-naudia medications like Promethazine. Those are usually more taking advantage of the antitussive properties of coding. And so things like Coding and chlorifeneramine, pseudofedran, for coughing cold, are coding with Promethazine. Another common liquid medication that Promethazine can help with the nausea and things that are associated with the coding as well. So there's still some formulations that are out there. Although, again, like coding isn't something we typically think of more or talking about prescribed opioids for pain management. The coding does carry a box warning for the risk of respiratory depression and death if given to children because of the patient being a CIP2D6 ultra rapid metabolizer. So basically having a genetic polymorphism at that particular Cytocrom P450 enzyme. And one of the main reasons-- until pharmacogenomic testing becomes way more widely utilized, a lot of times patients aren't going to have any idea that they would be an ultra rapid metabolizer. And so if we were to give this to a child who metabolizes much quickly, this being a pro drug, they may have a much higher concentration of morphine in their system than we would be anticipating. And so coding is a contraindicated, like I said, in children under the age of 12. But a lot of times we still don't use it until patients over the age of 18, especially if they're a teenager and they have some kind of concomitant sleep apnea or lung disease or something. Then we typically don't use it. Also not typically used in pregnancy or breastfeeding. And just because of that box warning on there, if you were to ever use it in a younger patient, you just have to verify they're not a 2D6 ultra-epid metabolizer. Typical adverse effects, though. GI issues, constipation, being the more common things decision from an adverse effect profile and still the risks of long-term opioid use, just like any others. Then we have the semi-synthetic opioids heroin is a semi-synthetic opioid. And of course, we don't use it for medical uses, but it does come from the poppy plant. It's considered an illicit drug. It's highly addictive and abused by many, many people around the world. But what we do use in medical instances would be-- one would be hydrocodone. It has oral formulations, various types, IR and ER and different brand names. It comes in combination with a variety of things. Like acetaminophen. There's a liquid antablet version of that. Chloropenaramine, kind of like the coating does-- liquid and capsule version of that. That's for cough. Also for cough would be the hydrocodone homeotropin combination liquid and tablet version of that. You also see hydrocodone combined with ibuprofen. And there's a tablet version of that. So hydrocodone is a pro drug of hydromorphone. Typically, its daily dose is limited by the acetaminophen component, because that's what it's most often prescribed with is the combo of hydrocodone acetaminophen to less than 3 to 4 grams per day, depending on the recommendation you look at in the other comorbidities for acetaminophen. Adversifix are going to be the same constipation, also nausea. Typically, you might see this a little higher rates of the side effects compared to oxycodone. One of the ER formulations is high singla, and it has a warning about QT prolongation for doses that are greater than 160 milligrams per day. Also, you want to use caution in patients with liver dysfunction and avoid alcohol consumption, if possible. It has a box warning for 3A4 related to a 3A4 metabolism, so that there's a recommendation to use caution when initiating 3A4 inducers or stopping 3A4 inhibitors, because it can lead to fatal overdose. Notably, hydrocodone is metabolized by 3A4, as well as 2D6. And the hydrocodone is a pro-drug of hydromorephone. And so you also will see hydromorephone used as the active drug that's another opioid that is widely used, especially in patient setting and whatnot. It is available as an oral formulation, both in immediate release and extended release. There's an extended release version called exalgo, which does carry a warning that says it's contraindicated if the patient is opioid naive. So you wouldn't see this in acute setting. The IV formulation is-- there's standard concentrations, and there's even high potency, 10 milligrams per ml concentration, as well. Obviously, the being IV, it's going to be more of an outpatient. There are an inpatient setting, in most cases. And it carries a box warning for making sure that patients are started at low dose, and then also using caution when converting from other opioids to hydromorephone because of the high risk for overdose. And it's thought to cause less nausea, paritis, compared to something like hydrocodone. But still can cause problems. Definitely can still cause the constipation. You'll also see hydromorephone used a lot in the patient controlled analgesia, the PCAs, that have a lockout time where they can administer their own pain medication over a certain interval. That hydromorephone is widely used in that regard, as well. So oxycodone available in IR and IR formulations. It also has an IR and IR formulation that has an abuse deterrent that comes along with it. And there's a few brand names for that oxycontin, oxydo, extams, then oxycodone. Also comes in combination with acetaminophen. It's a pro drug of oxymorphone, highly analgesic, even though it has a low affinity for the mu receptors. It has a box warning, as well, for the initiation of C3 or IV inhibitors that can lead to a fetal overdose. Because C3 or IV as well as C2 or C6 is involved in its metabolism. The extamsa ER capsule can be opened and the contents sprinkled on soft food or throughout a gastric tube, so that can be helpful for certain patients. A lot of times you might see the liquid versions of morphine being used in situations like that. Dosing adjustment is required for hepatic and renal impairment. And the active component of oxycodone being oxymorphone is also available as well. Different formulations. There's a immediate release and extend release, oral form and IV formulation. And then typically oxymorphones and patients are encouraged to take it on an antistemic if they're taking it by mouth. One of the opioids that does kind of, I guess stand out in my head anyway is Tependylol or Neusentah is a brand name. Now it is a opioid, but also has norepinephrine and serotonin reuptake inhibition properties as well. And because of that, maybe better option for pain that's associated with nerve injury, spinal cord injury, something like that. And then tends to be the early thought of as having lower severity of GI effects. It is contraindicated if the creatinine clearance is less than 30. And because of its effects on those neurotransmitters may increase the patient's seizure risk. And obviously if they're on other serotonergic medications can increase the risk of serotonin syndrome. So you have to use caution with that. But if you do have a patient with that chronic pain and associated nerve injury, that may be an option to consider if you are going to use long-term opioid. - Right. There's also a drug called Mepyridine, branded as dimmerol. It has an oral and I am formulation. Elderly patients or patients with renal impairment have an increased risk for CNS toxicity, including seizures. So that's something a warning to be aware of. There can also be a risk for serotonin syndrome when used with other serotonin or drugs with dimerol. It's typically not recommended, so you're not going to see it as much. Interestingly, it has an off-label use for postoperative shivering. Yeah. Paradian, I think the only time I ever see that is like dentists. That's what I exactly thought of that. I don't know what that is. I'm sure there's a reason why I'm using it. I'm not using it for a lot of personal procedures. I know I do. Another commonly used medication, although not-- I don't see it as much for actual pain management, more so for opioid use disorder, but buprenorphine. So buprenorphine does kind of have a unique mechanism of action. And so it is something that works as a partial muaginist, although as the dose goes higher, it can kind of convert into becoming an antagonist of the mu receptor. And then also is a weak capa antagonist as well. So the thought is that the risk of respiratory depression and whatnot is going to be lower. When we're talking about using buprenorphine for pain management, it's given as a transdermal patch under the brand name butrans. That's the actual formulation that's approved for pain management. One thing to note with butrans is that it can cause a QT pollination. If you're using a dose of 20 micrograms or more, there are lots of other formulations. When we were talking about buprenorphine being utilized for opioid use disorder, so there's subcutaneous injections. There's an implant injection. There's a patch, I'm sorry, not a patch, the patches for pain. There is a pre-filled syringe that can be given oral formulations combination with naloxone. So there's suboxone, which is available to film in a sublingual tablet. There's bucule, the formulations. There's other strengths available compared to regular suboxone like Zubzol, there's a different kind of strength in combination, but all of those are in combination with naloxone, which the naloxone, remember, the opioid antagonist, that piece of it doesn't actually get activated unless the patient alters the formulation. Like if they were to take the tablet or film and melted or so in other words, trying to inject it as opposed to taking it the way it's designed, the naloxone kicks in and negates the effects of the buprenorphine altogether. So that's kind of like the abuse to turn that's built in. But those types of formulations, again, are used for opioid use disorder. You know, when you're trying to get a patient off of opioids or helping them stop heroin or whatever it may be. But the patches can be utilized for just overall pain management and maybe a little bit better from a safety profile as well. OK, so synthetic opioids, probably the most notorious of those, is fentanyl because of the opioid crisis and the high risk for overdose, which is primarily because it's just so potent. It has a really high potent, so you 100 times more potent than morphine. It's lipid soluble. It crosses the skin and oral mucosa, which is dangerous for people who are interacting with folks who are abusing fentanyl like first responders and police officers and things of that nature. In medicine, it's only to be used for patients who are opioid tolerant. It has pretty low biopilability. But it does have various formulations, non-oral formulations like IV. There's a buccal form, a transmucosal logins, a loz hinge, and then a transdermal patch, which is probably the most common outpatient one that I see. It's active for eight to 16 hours after the patch is removed. It is safe and renal failure patients, and there's also sip-3-afformatabolism to consider. Heat increases the release with the transdermal formulation, so don't use a heating pad, which of course, if you're placing it directly on the side of pain or something like that, if that's what the person ended up doing, like they're back and then they're using a heating pad that could be a problem, or heating blanket, or heating lamp like the attaining bed, for instance, or a sauna, right? Go and hang it out of the-- at the lodge. And then what people do with your fentanyl-- With your fentanyl patch on. In the sauna, they'll do that. Don't cut lick to freeze or inject the patch. It's also recommended to fold the patch before disposing of it for safety reasons. fentanyl seems to have less constipation than some of the other opioids. It has an onset of action of about 12 to 16 hours. The duration of each patch is about three days. But it does have other adverse effects-- Bradycardia, confusion, dehydration, muscle rigidity, thanks to consider. Another option is out there, but again, not seen-- or not used as nearly as often for pain management, as it is for opioid use disorder, but methadone. Methadone has some weird properties to it. It's got a really long half-life. Anywhere from 22 to 48 hours, depending on the dose that's in hell, often they've been getting doses. Like I said, nowadays is used much more commonly for helping a patient with opioid addiction. And so the patient will go to an actual opioid-- I'm sorry, a methadone clinic-- and then get their dose daily for a substantial amount of time, and then they can slowly work their way through the program where they're getting doses to take home and whatnot. But it's a whole very strict process that goes into that. Does tend to have a little bit better set of profile, although constipation, even in the case of using it for opioid use disorder, the constipation can still be really problematic with methadone. And it is something that we-- if you are going to see it being used for pain, is given multiple times a day. When you see methadone prescribed one time a day, it's for opioid use disorder. And it's most likely being given at a methadone clinic. But if a patient is taking it multiple times a day, that would probably indicate that they're using it for pain management. Methadone does have some serotonergic properties to it as well. And so if a patient's on other serotonergic medications, serotonin syndrome should be monitored or the risk of serotonin syndrome. The box warning that's associated with methadone is in regards to the risk of QT prolongation. So if they're on other medications, they can prolong the QT interval. They have a history of arrhythmias or baseline hypomanganemia, something like that that would put them at higher risk for developing torsads. That would definitely warrant closer monitoring and making sure that that QT interval isn't increasing. But still an option out there. You'll see it sometimes, but much more of commonly seen in opioid use disorder than actual pain management. We did want to highlight the primary opioid antagonist, Naloxone, which Mike mentioned before, branded as Narcan, used in the cases of opioid overdose. And a lot of instances recommended to be prescribed alongside the chronic use of opioids or even the short-term use in patients who are at high risk for overdose. It's a pure opioid antagonist that competes and displaces opioids at the opioid receptor sites. It's an intranasal formulation. Narcan itself is an intranasal formulation. And I believe-- just off the top of my head, I'm pretty sure there is a different formulation as well. I'll verify that in a minute, but I am or something like that. Anyways, the intranasal formulation is 4 milligram nasal spray that you use as a single dose in one nostril. It can be repeated two to three times in different nostrils until medical assistance becomes available. It's good to know that it will cause an acute opioid withdrawal. So this can lead to pain, anxiety, to kidney, anger from the person you're using in an independent situation. You want to monitor respiratory rate, heart rate, blood pressure, their temperature, the level of consciousness, pulse, ox, et cetera. There's just for a lack of time, we won't go through all these. But there are some resources you can utilize for things like converting from one opioid to the other. There's lots of different versions of the equinogegic properties of various opioids that are out there. But pearls, a long time sponsor and friend of the show, has a great chart kind of on the different opioids that are out there. And they're equivalent doses if you are going to switch from one to the other. And then also the-- CDC in general, they have an opioid guidelines mobile app that you could download and it talks kind of about obviously getting patients, the best safety protocol in place as far as them being on chronic opioids. It talks about calculating the morphine equivalence and how the total exposure that they're getting on a daily basis from the opioid and prescribing guidance and motivational interviewing strategies for patients who are dealing with chronic opioid use and things. But it's an app you can download for free, both Google Play and the Apple app store. So definitely encourage you to check both of those out and lots of other resources that are out there. But those are two that I know I've used personally. And then just quickly just to end things, I do want to reiterate, call it already mentioned this. But when you have a patient being started an opioid for any length of time, it's always a good idea to consider a bowel regimen because opioid induced constipation can be a real problem for patients. So at the very least, having them get over the counter like a scena with or without a stool softener like coalesce, typically a good first line starting treatment for patients who are going to be on opioids. And if the constipation becomes problematic even with the over the counter products, then there's several different prescription options that are out there like the methyl-nil trixone, which is realistore. So there's a couple other things like movantic is another one that's a tablet that you can take. I will say personally, one drug that I've had good success with, especially in patients who are like on methadone for opioid use disorder and they're taking it chronically, lens S. So it's not FDA approved but does have lots of different studies showing efficacy for use in opioid induced constipation. And now that it's come down a little bit in price, it's a lot more widely available in different insurance formularies and stuff. I've definitely had some good success with lens S and patients that are on chronic opioids and something to consider amatizes often are also approved for opioid induced constipation but lens S tends to be my, if I need something with a little bit more kick to it, besides like Senna and Colase, lens S tends to be the one that I'll try to go with if possible. But just wanted to throw that in there at the last minute. 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