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Articles

Public health and infectious disease experts offered their perspectives on the 2024 US bird flu outbreak and its potential of becoming a greater public health crisis.

H5N1 Bird Flu: A Slowly Looming Public Health Threat

On the most recent episode of Over the Counter, James Rider, PharmD, joined Drug Topics to discuss his career journey as a chain pharmacist. 

Chain Pharmacist Embracing Expanded Role in the Profession

Researchers explored the benefits of tai chi and prevalence of liver disease in patients with osteoarthritis.

Tai Chi Intervention, Liver Disease Prevalence for People with OA | ACR Convergence

Research presented at American Heart Association’s 2024 Scientific Sessions examined the SGLT inhibitor’s effect on systolic blood pressure.

Sotagliflozin’s Effect on BP Remains in T2D Regardless of Kidney Function | AHA 2024

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Clinical

Revolutionizing Acute Pain Relief: Emerging Non-Opioid Therapies and the Essential Role of Pharmacists

Child Abuse: Responsibilities and Protection of the Reporter

The Impact of Pharmacists and Pharmacy Technicians in Recognizing and Responding to Human Trafficking (Pharmacist Credit)

1.0 Credit / Law, Pain Management, Opioids


Ensuring Pharmacy Technicians’ Proficiency in Risk Evaluation and Mitigation Strategies

PROMIS scores demonstrated the disparities between reported pain and mental health outcomes.

Disconnect Between Adolescent, Caregiver Pain and Depression Symptoms in Rheumatic Diseases | ACR Convergence

The FDA has mandated that companies participating in the Opioid Analgesic Risk Evaluation and Mitigation Strategy program provide pre-paid mail-back envelopes for unused or expired opioid medications.

FDA Expands OA REMS, Mandates Mail-Back Envelopes for Opioid Analgesics

The addition of a 10 mg oxycodone hydrochloride tablet improves dosing flexibility and precision.

FDA Approves Abuse-Deterrent 10 mg Oxycodone Hydrochloride for Severe Pain

Opioid use disorder risk was higher in a cohort of patients with chronic pain without disability. 

Rates of Opioid Use Disorder With Gabapentin, Benzodiazepine Coprescription Evaluated

The 70-plus-page lawsuit is directed at Express Scripts for its dealings with drug manufacturers in fueling the US opioid crisis.

Kentucky Sues Express Scripts for Role in Opioid Crisis

Albert Dahan, MD, PhD, talks about the first-in-class dual-NMR agonist cebranopadol.

Could an Investigational Therapy Help Fill the Gap in Pain Management?

In the field of pain management, there are many gaps that continue to exist and adequate pain management is often not achieved. When pain is not sufficiently managed, it can lead to negative long-term effects on a patient’s physiological and psychological health.

 Higher pain intensity and frequency can also develop into chronic pain, which currently impacts around 20% of adults in the United States.

Opioids have been considered an essential medication for pain management, but they do carry significant risk. Research has shown that there is a lack of data to support long-term benefits of opioids for chronic pain.

 That data also showed that long-term use of prescribed opioids put patients at a higher risk of overdose and opioid misuse. This is why other medications that do not carry the risk of severe side effects are needed.

Tris Pharma, a biopharmaceutical company working on drug development for ADHD, pain and addiction, recently presented data from a clinical study on cebranopadol, a first-in-class dual-NMR agonist that targets the nociceptin/orphanin FQ receptor and the µ-opioid receptor. Data showed that the therapy produces potent and prolonged analgesia with 25% less respiratory depression than oxycodone.

 The company believes cebranopadol could be a “potentially transformational new pain therapy.”

 recently talked with Albert Dahan, MD, PhD, professor of anesthesiology at Leiden University Medical Center and a researcher on the cebranopadol study, about what cebranopadol is and how it’s different from traditional opioids, how it will fit into the broader landscape of pain management therapies, current gaps that exist in pain management and how the therapy might help address them, and what the next steps are for cebranopadol.

“I’m writing currently a paper on psychedelics and pain management,” Dahan said. “People use that. Why do they use that? Psychedelics are not at all drugs that you would like to use because they have psychedelic side effects: disassociation, hallucinations. The reason is, we don’t have drugs that are safe. We don’t have drugs that allow the patient to experience profound pain relief without side effects. People except these side effects because they think they’re safe…I really believe—I’ve done 2 studies [on cebranopadol] that were both quite good—that we’re reaching an area that is very interesting.”

1. Varsi C, Ledel Solem IK, Eide H, et al. Health care providers' experiences of pain management and attitudes towards digitally supported self-management interventions for chronic pain: a qualitative study. BMC Health Serv Res. 2021 Mar 25;21(1):275. doi: 10.1186/s12913-021-06278-7. PMID: 33766028; PMCID: PMC7992849.

2. Rikard SM, Strahan AE, Schmit KM, et al. Chronic Pain Among Adults — United States, 2019–2021. MMWR Morb Mortal Wkly Rep 2023;72:379–385. DOI: 

3. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain 

 United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1–95. DOI: 

4. Findings Presented at PAINWeek 2024 Demonstrate Tris Pharma’s Investigational, First-in-Class Therapy Cebranopadol Provides Potent, Prolonged Pain Relief with Improved Safety Over Oxycodone. News Release. Tris Pharma. September 3, 2024. Accessed September 12, 2024.

Videos

Albert Dahan, MD, PhD, professor of anesthesiology at Leiden University Medical Center, talks about the first-in-class dual-NMR agonist cebranopadol.

Could an Investigational Therapy Help Fill the Gaps in Pain Management?

 What are the key takeaways from your study on the barriers to medication for opioid use disorder (MOUD) treatment during incarceration?

I think there are 4 key takeaways from this study. One is that people who use drugs in our study were largely supportive of medications for opioid use disorder treatment or MOUDs. I also want to note, though, that we did see themes that reflected that things like stigma, racism, and discrimination may impact how people feel about treatment, and also their likelihood to start MOUDs. For example, a common concern was that using MOUDS would trade one addiction for another. This is largely a stigma that's resulted from treatment systems historically favoring abstinence as the sole goal of treatment versus being more open to medication-based treatments as well.

Secondly, there's just generally more medical and substance use disorder support needed during incarceration. Treatment for opioid withdrawal, which when not treated is painful and life threatening, can be very rare in incarcerated settings. People also really supported the idea of accessing treatment during incarceration for MOUDs and said basically ‘it's easier to stay clean than it is to get clean.’

Thirdly, trust is really important with this community, Black, African American, Native American, Hispanic, Latinx, and multiracial people who use drugs in our study supported themes of self-blame and being dropped from services after one mistake more often than White respondents. These types of experiences can reduce trust in our treatment systems, which ultimately can make people hesitant to access them. To that end, it's really important to acknowledge the collective and continuous trauma that people who use drugs face, and that these traumas are more concentrated among communities of color as a result of things like structural racism and white supremacy that play out at different levels of our system.

And then lastly, a very commonly supported theme in our study was that people wanted to be treated like humans. A common ask from participants was just to experience empathy, authenticity, and nonjudgmental understanding from our systems when they do reach out and seek help.

 How can pharmacists help address these barriers?

 I think one of the quickest ways they can address these barriers at multiple levels is just being a partner, and spreading evidence- based practices throughout our systems, including not only to their patients, but also to the partners that they work with. One example of how this might play out is that methadone can be dispensed outside of an opioid treatment program for up to 3 days to continue treatment. Accessing methadone is often challenging for jails and prisons because of the strict regulatory requirements that it has to be delivered in an opioid treatment program. This would permit methadone to be provided, for example, when a community opioid treatment program is closed on a weekend, or an individual within a really brief sentence in a jail who just needs to be continued on their treatment. Pharmacists would be permitted to actually dispense in that scenario under that kind of 72-hour rule.

Another discussion point around advocacy for pharmacists is that the Department of Justice in April of 2022 released guidance that protects a person with an opioid use disorder’s right to MOUD treatment, noting that not providing it in different settings, including incarceration, is a violation of the Americans with Disabilities Act. The first point is just to be a partner in spreading these evidence-based practices. The second piece is to dispense MOUDs. If you receive a prescription, make sure you're filling and dispensing it. Prescribe them if you can, which really depends on the state. So, check in with your local state laws.

Thirdly, consider partnering with people from other sectors like the criminal legal system to improve medication access. Depending on your role, you could be a key partner in those types of relationships. I think we've learned a lot in Marin County about the power of bringing multiple stakeholders together to tackle a complex problem. We launched a community collaborative in 2014 that was really led by the community to address the prescription opioid crisis at the time. They've now shifted to focusing on the overdose crisis. As part of that community collaborative, they work with law enforcement, criminal legal system, health care, pharmacists. I think sometimes just having the right people in the room to talk through these really complex problems can be a really fruitful place to move forward and move the needle on these health outcomes.

Lastly, just support and attend trainings related to harm reduction and trauma-informed care. As I mentioned, a lot of people in our study noted that they felt that they had faced stigma and judgment from our different treatment systems. The more people are trained and can understand that trauma-informed approach and the value in harm reduction practices and frameworks, the more that will arm them with the authenticity, empathy and understanding that people were really asking for.

So just to summarize, the 4 things I think pharmacists can do to help address these barriers include being a partner in spreading evidence-based practices throughout our system, dispensing MOUDs because they save lives, consider partnering with people from other sectors like the criminal legal system, and support and attend trainings related to harm reduction and trauma-informed care.

What’s next for your research in this area?

 We're working on producing resources that can be shared more broadly with stakeholders and community members, including sharing these results back to the community of people who use drugs, ideally through a forum where we can discuss and get their thoughts on all of this feedback. I'm also working on finalizing 2 additional analyses related to evaluating jail based MOUD treatment in California, that were part of my PhD dissertation projects funded by the National Institutes of justice. The first is a multi-county study that evaluated how offering opioid agonist therapies like methadone and buprenorphine, in county jails influence county-level emergency department visits, deaths, arrests, and convictions. We're also currently working on publishing this work in a peer-reviewed journal so that we can continue sharing it with other folks and kind of permeating what we learned from the great folks that participated in this study.

I'd love the opportunity to share a quote from one of our participants. They were talking about the importance of meeting people where they are physically. “So, a lot of people don't go to the doctor. They just don't make it past their 10. They're stuck in a rut. There should be a global bus that reaches out to them, because they don't like to reach out to you guys. We have a hard time with that. But I think there should be more outreach.” I would say that the importance of meeting people where they are physically also translates to meeting them where they are in their substance use disorder, emotionally and mentally, no matter what the starting point might be. Participants throughout our study really talked about how important open, understanding, and nonjudgmental relationships have been for them, and that a lot of them ended up entering treatment as a result of those kinds of kind, nonjudgmental relationships. I would say that a great piece to end on is meet people where they are physically and also emotionally and mentally in their current substance use disorder.

Haylea Hannah, MSPH, PhD, discusses her research on the barriers to medications for opioid use disorder that people who are incarcerated can face and what pharmacists can do to address the barriers.

Addressing Barriers to MOUDs Faced by People in Incarceration

 What are the things that we can do to try and help educate people, to try and make sure more people know about Naloxone, people know more about opioid use disorder? If you could give people more of what you want them to hear, get on your soapbox and tell me about it.

: I want make a plea to primary care to be more mindful of the fact that we’re undertreating pain and we need to ask about the pain and come up with something that’s more comprehensive psychologically, biologically in every manner of treating the pain. What we’ve done is we opted for the obvious and quick solution by doing opioids. That’s how for a decade we treated people that complained of pain, and we got into trouble with that. What we did then is we withdrew all of that medication and didn’t really address the underlying chronic low back pain from the failed back surgery or the fibromyalgia or the chronic daily headaches or the irritable bowel. We just ignored that, and we need to pay more attention to what other options patients have available. We need to address the pain, and if we do that, it is less likely patients are going to go to the street to get their access to pain medicine; that is no. 1. No. 2, what I see my colleagues doing in California since this requirement is they say, “Well, by the way, here’s a prescription for Naloxone. If you have an overdose that will take care of it. You just need to read the literature.” They’re given that. Without having a longer family visit about how dangerous these drugs are, if they’re going to use them. How dangerous the internet is and how available medication is on the internet, even though it shouldn’t be, and that if they dabble with that, for whatever reason, the chance of them having a death is much higher and that they should become very comfortable with how to use the medication. I was especially impressed with the studies that showed when you had a prescription in a patient’s hand of Naloxone, whichever form they had it, the chance of that patient overdosing is much less. It’s not because they’re using the Naloxone. If they looked at refill rates or how many times they went to the ER [emergency room], they went to the ER less when they have the Naloxone. Not because they used it, but because they were aware of how serious it was. The doctor gave me this medication. The patient says, “Man, this other stuff I’m taking that I have to use this injection for must be pretty serious or he wouldn’t have given me that.” Patients are getting the idea that these pain pills are really dangerous and they shouldn’t take them and we should have that discussion with the patient now when we have the Naloxone, as opposed to just an off the hand, here’s some medication in case you overdose the way we’re doing it now.

: I was just going to say, I would add from a pharmacist perspective is that you have that benefit of having that full profile in front of you and looking for other risk factors. Like we’ve all said, there are times a person may take something and not realize the risk or ramifications. You can highlight that and help them realize that they need to take those medications, respect them for their potential potency or effects, and acknowledge that there are ways to reduce that risk by reducing the opiate burden per se with non-opiates so OTCs [over-the-counters], non-steroidal, other non-pharmacologic, and to communicate clearly with practitioners. The other is to educate on the importance of how properly to administer Naloxone, the role that it plays. Like we’ve said today, when one of those moments happen, that’s a moment that needs additional care and follow-up to evaluate. That risk of reemergence of signs and symptoms don’t look at it as a 1 dose is going to be it for sure. That window afterwards is a critical window to watch for potentially needing to re-administer.

: I have to say it’s hard to add much to all of the comprehensive discussion that we’ve had and the points that Dan and Bill have raised already and, of course, we’ve all raised during this extended discussion. I think the recognition from my perspective as a psychiatrist of comorbid psychiatric disorders among patients who have substance abuse just cannot be emphasized enough. The patients who I typically see come in saying they have, or their family member says they have some substance abuse problem, and they want you to fix it, most frequently it’s because junior does not have the substance problem. What he has is serious depression and he’s, in fact, self-medicating it. This was frequently the case when I’d have high school students or early college students being brought in by their parents saying, “Johnny’s failing at school. He’s at the best places and it’s all going downhill now. I think he’s using some drugs.” The truth was he was using some drugs, and this was a time where the fentanyl was just starting so he wasn’t dying from those drugs, but what he had was serious problems with depression. Treating those depressive disorders is key. If you only take care of this substance abuse and you don’t do anything about the comorbid psychiatric disorder, you’re bound to fail just like psychiatrists have always been accused of trying to make the depression better or make the psychiatric disease better and the substance abuse will take care of itself. Well, that’s certainly not true. You got to take care of both of them and the both of them is the most common kind of presentation that we’re going to see. You have to be prepared to do something about that. Now, whether every primary care doctor is going to be savvy to this, I don’t know. There are lots of people that have the buprenorphine waiver, for example. The average number of patients that many are treating is 3 to 4 patients. It’s clear that we have enough providers for these interventions, but we don’t have them treating enough patients. They’d all have to treat 30 patients or so for us to match what the epidemic proportions are. More providers need to be engaged. They have to have an open mind that substance abuse and major psychiatric disorders are not totally divergent, that they, unfortunately, are totally convergent and come together. You can die of suicide. You can also die of an overdose just as easily and a whole lot more quickly.

: Matt, that brings up a point I want to also make is I had a recent overdose rescue in my practice and what struck me was that the wife said, “I didn’t know if I should give it or not. I couldn’t tell. He sleeps really deeply, and I oftentimes have trouble waking him up normally, not when I’m even worried about him.” The question comes up should she use it when she’s not sure? Should we be advising family members to use the drug if they’re not absolutely certain that it’s an overdose? The side effects, the risk-benefit profile for using the drug is so much in favor of using the drug if you’re not sure because of the fact that there hardly are any side effects from the drug. There are withdrawal side effects, but if you don’t know, it’s better to use it than to not use it because a side effect or a withdrawal is much better than a death. If you don’t know for sure, err on the side of something that is less harmful to the patient.

 Amazing. Another great point. Way to go you guys. I think that just to sum it up, I would say, an overdose is a real thing and it’s prevalent. It’s powered mostly by illicit fentanyl products which have completely taken over the illicit drug market so anybody who’s getting drugs from the internet or from drug dealers, they’re likely to have fentanyl in them. It’s incredibly dangerous and that Naloxone can be lifesaving. In order to have the benefits of lifesaving drugs like Naloxone, you’ve got to have them. They’ve got to be in patient’s hands. Then we got to work on increasing access, increasing education, and trying to save lives, which is our primary job. I think we’re basically out of time, but I just want to thank each of you so much for your time and attention and the expertise that you’ve offered to this session. It’s been incredibly informative. I’ve learned a lot and I really appreciate your hard work and dedication to this. Thank you so much.

This transcript has been edited for clarity.

The panel concludes our discussion with the role healthcare providers play today in the treatment of opioid overdose and what needs to change for the future.

Video Series

The Role of Healthcare Professionals and Future Directions

 What does that make us think about in that case? What do you think?

: I think several things that I wonder about in this. Is this a guy who just out of the blue, who decided “Let’s go buy some opiates at the local gas station and use them?” There seems to be like we’re missing something in this. High school just isn’t enough of an excuse. I think you have to think about longer term treatment, and I think based on the 8 mg of Naloxone that it took to reverse him and what’s on the street then he probably did get fentanyl in that. Then, the question is what do you want treat him with? Could you treat him with naltrexone? An injectable naltrexone lasts a month, so you don’t have compliance problems. Well, if he’s not opiate-dependent, that’s a real possibility, but I would first check how dependent is he on opiates. Assuming he is, then you’re really talking more likely about buprenorphine, and the buprenorphine dosages, as we said, are minimally now, probably 12 to 16 milligrams a day. Many people get up to 20 milligrams certainly in the VA [Veterans Affairs] population where average dose is 24 mg a day that people are getting. Much higher than we used to use. Now, will that dose block fentanyl? I realize we keep talking about fentanyl and the answer is that dose of buprenorphine will not. It’ll block every other opiate, but it won’t block fentanyl. What could you do? Well, there’s been a recent report sponsored by actually the company that makes the depot buprenorphine, that if you give depot buprenorphine at the 300 milligram dose every month, you get blood levels that are in fact sufficient to block certainly therapeutic dosages of fentanyl, but potentially, maybe twice the dose which would, of course, be potentially a lethal dose in some people. I think that it raises interesting questions about what new treatment alternatives we need to think about. One of them might end up being monthly 300 mg of injectable Sublocade, which is different than the FDA [Food and Drug Administration] guidance, which is they give 300 initially, but then typically shift to 100 per month. If you wanted to keep those blood levels up above 6, which is what you need to do to make it work against fentanyl, you’d need to give 300 every month. There’s no data by the way about whether naltrexone at the standard injectable doses we have, if that would block fentanyl. It will block all the other opiates without a doubt, but whether it will for fentanyl is not at all clear. There are some very interesting questions that get raised about this. What’s hidden behind that curtain of his chronicity with opiate use and what are your options?

: Tom, would he have access to the drug? Namely, would his health care provider if it’s an HMO [health maintenance organization]? If he’s Medicare? Now, he’s 49 years old, so he’s not Medicare and he’s working so he is not Medicaid. Would he have coverage for that, or would it require prior authorization?

: Well, I wish I could say that prior authorization, who would think to do that? Every insurance company apparently thinks to do that and puts you on the line with the social worker to say why you can’t prescribe this medication, which I’ve done. Usually, the injectable medications tend to be on the medical side of the benefit rather than the psychiatric side of the benefit and that’s a huge advantage because they’re used to paying for more expensive things on the medical side I’ve found. When you tell them how much say, just if I can mention a trade name, Sublocade would actually cost for 300 milligrams a month, they don’t bat an eye. If you did that for a psychiatric patient, they would just hang up the phone. Again, I bow to Dan’s expertise on this in terms of anything around cost. It’s not cheap. There’s no 2 ways about it, but I don’t quite know. Dan, do you know much on that?

: Well, there’s a couple of issues packed in there. One is that a lot of pharmacies, like I said, do have access to discounted programs. Certainly, as new products come out there are incentive cards for discounted pricing for patients. That’s something to talk to the manufacturers about but there are state programs from state to state that provide it. Tom, I think you brought up an important point on this case. It doesn’t seem to be complete and one of the issues is this should be a wake-up call. Look at psychosocial factors, the risk factors for depression, the risk factors for substance use disorder. This is an opportunity and I think a commonly expressed shortcoming is to know where do you route these people for that next type of intervention? The other is Matt, I think you brought this up earlier, if used, and we don’t know much about this patient’s background is that’s what we’re talking about now, this would’ve been a moment that is followed up by EMS [emergency medical services] and an intervention for continued monitoring even if it’s to get them routed to some type of support program to get them started. Bill, you brought it up is, and if they don’t have access, and if it does turn out that they are a repetitive user and significant at-risk behavior, then they should be provided the supportive care of access to Naloxone products.

 By the way, great guys, you guys are amazing. I would say that number 1, this person absolutely needs comprehensive individualized multimodal treatment over time that’s biologic, psychologic, social, spiritual, and nutritional to have the best possible chance of overcoming his challenges. We just got what happened in the ER [emergency room]. They don’t know anything about him. Unfortunately, the ER has never been great at routing these patients into treatment, but fortunately, it’s getting better and better and better. In California, some ERs are even starting buprenorphine, which is amazing. Because you could give this guy Sublocade if you had it in the emergency room right there. You could start them on buprenorphine. You could refer them into treatment. There are so many things that you could do with this teachable moment, but I’m afraid that in real life, many times this guy wakes up and goes home, and not much else happens.

: That’s definitely true, Matt. I see this as a primary care issue because all we have is he has chronic pain, had an opioid use before, but we don’t know what his chronic pain is. How much medication is he taking? What has been done to that chronic pain after this MVA [motor vehicle accident]? Has he been evaluated by physical therapy? Is he on any kind of nonsteroidal? Is it musculoskeletal? Would duloxetine be a valuable adjunct for him to treat his probable depression since he's lost his job in addition to that? I think all of those things need to be addressed and primary care is really a good place to do this because the primary care provider probably knows this patient pretty well, knows the family, has got the inside and outs of what’s happened to this job loss and could really follow up on this in a more comprehensive manner and get to the bottom of it, to send out referrals where needed, and not have this happen again. This guy got very close to dying if you can see, a heart rate of 28, blood pressure real low, and it is not that unusual for him to have something happen like this again if he's not adequately addressed and evaluated right now. It’s the wake-up call like you say, and we need to take the handle on this and run with it because he’s going come in dead next time.

Our experts provide their expertise on Patient Case 2 and how they would proceed with treatment.

Patient Case 2 Discussion

 Well, let’s talk about another case. In this case, it’s a 49-year-old man found semi-responsive to commands with suspected opioid overdose. He has a past medical history for high blood pressure, diabetes, obesity, chronic pain, opioid use following [a] previous motor vehicle accident. He’s a truck driver. He smokes a pack of cigarettes a day. He was recently divorced. He has previous recreational drug use in high school. He has no local family besides his ex-wife. He lost his job due to the COVID-19 pandemic. In his physical exam, he’s hypertensive, he’s unresponsive to sternal rub. On clinical workup, he’s got pinpoint pupils, he’s pale. He has clammy skin. His blood pressure is 60 over 40. His heart rate is 28. For treatment he’s given supportive breathing confirming his airway is clear. He gets 8 mg of Naloxone intranasally. He’s monitored for times of opioid withdrawal and/or non-Naloxone resistance. Repeat Naloxone dose if needed for symptom return, educate patient on risk associated with chronic opioid therapy and prescribe emergency use of antagonist as a safety measure if the opioid use continues.

Dr Torrington moves on to Patient Case 2, a 49-year-old man found semi-responsive with a suspected opioid overdose.

Patient Case 2: 49-Year-Old Man With Suspected Opioid Overdose

 What do you think you’re going to do for this guy? Is he a candidate for naloxone? What do you think so far?

 I’m curious about the fact that he’s being given an opioid on top of the fact that he’s already taking a partial agonist drug buprenorphine. Ostensibly, that medication is for his opioid use disorder. I don’t understand the dose, but that’s why he is taking it. If you were given an appropriate dose for opioid use disorder, this amount of opioid in addition probably wouldn’t treat his pain very well either because it would be antagonized by the buprenorphine.

I’m curious about this whole setup. I don’t know if it’s unrealistic because I don’t know if the ED [emergency department] doctor knows the buprenorphine and the opioid together may not be a good combination. You may need to use more of the opioid if you want to overcome the buprenorphine dose. It’s certainly a risky situation because, at a low dose, the patient may not get enough pain relief and may start taking more of the medication. If the patient was given 100 pills, he would certainly have enough medication to do damage and would need something like naloxone and a discussion with the family on how to use that drug.

But I want to point out that in something like this—the patient now is stabilized, they’re in a cast, they’re going home—there are other options for this patient. Certainly, a nonsteroidal should be thought about. It can be highly effective in a patient like this who has inflammatory pain. We already know the patient got IV [intravenous] Tylenol in the hospital, and his pain level went from 10 to 6. That’s how I read his pain record. Just from the Tylenol he had a lot of pain relief, so maybe Tylenol with a nonsteroidal without adding the opioid would have been a better choice for this guy because he already shows substance abuse disorder, and it’s going to be 5 days before he sees his primary care doctor. I’d probably have him back to the primary care the next day, so you can see how he did with whatever regimen you gave him. That’s how I’d deal with this.

 That’s a key point when we look at the transition from emergency department to home: trying to look at things that don’t create that scenario 5 or even 2 weeks till somebody gets into a particular practice to be evaluated. A more aggressive nonsteroidal would be beneficial, maybe even if there’s a concern over inflammation steroid upon leaving or a 3-day course to get them there as part of what may be driving some of that pain or discomfort. Clearly, a drive for communications on discharge is to specialty practice and shorter windows in that point for care.

As an alternative to this, I’m not sure exactly why he was getting the 2 mg of buprenorphine. But as an analgesic, buprenorphine at 2 mg presumably sublingual is quite a good dose for analgesia. It just doesn’t last that long, so you may have to give it 3 to 4 times a day to get actual analgesia from it. The advantage is that if you were then giving it, what would be the equivalent? At 8 mg a day, at least, that’s a dose that blocks many other opiates and things that he might overdose with. Buprenorphine is a good analgesic. It has a ceiling on it. This is the type of pain that I suspect would be more than sufficient. I bow to Bill’s expertise on whether he thinks that’s true, but these patients I’ve had that have taken 2 mg 4 times a day have gotten some remarkable pain relief from that as well because they’ve had opiates as a problem in the past. We’re dealing with that problem.

 I love all of that. I’ll add a few things. A) You can increase the dose in frequency of buprenorphine. B) You could be more aggressive with your N sets. C) If you don’t do enough to treat this guy’s pain, you can drive him to the illicit market, and that’s when he becomes the real victim of overdose. Part of the point is that I see a lot of substandard pain treatment, which makes even reasonable people go to the illicit market to get something else to help them with their discomfort. Humans don’t want to suffer, and they’ll take a path to help them alleviate their suffering. If we don’t do an adequate job, they’ll take matters into their own hands. I love all those points. That’s really helpful. In California, you’d be giving this person…a prescription for naloxone because anytime you prescribe a controlled substance, you need to do that. In other states, it could be totally worth it. Any other comments about this case before we move on?

 That dose of naloxone I prescribed would be the 8-mg dose because if he did go to the illicit market, unfortunately fentanyl might be in that. Then, you’re going to need a big dose of naloxone to do something about that.

 I want to point out that most of these naloxone compounds are covered by wherever they’re getting their medical care. But if they don’t have medical insurance, it can be very expensive. I called CVS, which has a furnishing ability in California. They don’t need a prescription, so the pharmacy can write a prescription under a state order that they can furnish the dose. I asked CVS, “How much does it cost the patient?” It’s $80 for the nasal Narcan generic, which is a hefty amount if patients don’t have a whole lot of money. If they don’t have insurance, it’s problematic. There are insurance cards that you can get in some places. But without insurance, it can run into a lot of money. You have to be aware of that.

 Bill, you raise a great point in terms of ease of access and affordability. We all get very busy in point-of-care activities, but if you track legislative initiatives in your own states, you’ll find that there’s a lot of those specialty access protocols. In many cases, there’s state-funded access to product for those who fall outside some other type of insurance. Thus, it’s important for each of us to look at what’s happening in our own states that impact our area and communities.

Such great points. As you’re saying that, I’m thinking to myself, “We should dispense the naloxone in the ED.” This guy just was in a car crash. We’re expecting them to go to the pharmacy and get this stuff, and then who knows. If it costs extra, they’re not going to get it. If people had to pay for an AED [automated external defibrillator], would they? No, but it needs to be there anyway. That’s something I thought of that makes sense.

 Matt, another thing is that this person has an opioid use disorder. I assume he was given the buprenorphine because of treatment for the opioid use disorder, even though it’s a subtherapeutic dose, but let’s just put that out there. He’s still drinking and smoking cigarettes, which put him at high risk for going outside the standard prescribing realm to get medication, like the internet. So he really is high risk given all these factors. This is the guy who needs naloxone and a discussion with the wife or the other members of his family about what to look out for if he overdoses.

The group discusses Patient Case 1 and how they would treat in this scenario.

Patient Case 1 Discussion

 Our first case is a 27-year-old man who presented with extreme pain in his right ankle, ribs, and arm after getting into a car crash. He has a past medical history, significant for substance use disorder, high blood pressure, and diabetes. He works from home, drinks 1 to 2 cups of hard alcohol when he’s stressed, smokes a pack of cigarettes a day, and is married with 4 children. He takes buprenorphine 2 mg per day, lisinopril 20 mg, and metformin 500 mg. He came into the emergency department [ED]. In the first hour upon arrival at the ED, he described pain as 10 of 10. He got 1 g Tylenol IV [intravenous]. In the second hour, he had 6 of 10 pain. There was no comment about his pain and what they gave him then. In the third hour, 7 of 10. In the fourth hour, 10 of 10. The imaging showed a hairline, a broken ankle, a broken rib, and a small hairline fracture on his clavicle. CT and MRI showed no tissue or brain damage. He got a cast for his right ankle and then got started on low-dose opioid therapy, Percocet 5/325 [5 mg oxycodone hydrochloride, 325 mg acetaminophen], 1 every 4 to 6 hours as needed for pain for 5 days until he gets to his primary care provider.

Matthew A. Torrington, MD, introduces our first patient case, a 27-year-old man presenting with injuries from a car accident.

Patient Case 1: 27-Year-Old Man With Car Accident Injuries

 How do you talk to the patient? How do you let the family member know what they would look for in their loved one who may be overdosing? It’s difficult because this could occur when they’re in bed sleeping and they wouldn’t even know about it. Multiple deaths have occurred that way. They take their first dose of methadone on the third night. After taking it, they’ve accumulated, and they’re dead in the morning. The discussion you have with the family is what it would look like: they’ll be overly sleepy, [it will be] difficult to wake up, [they’ll] act like they’re drunk and won’t be themselves. You should think about this being an overdose, and you don’t have a good explanation.

There’s no reason—they haven’t had anything to drink, they haven’t changed their dose—but the patient may be getting something that the family doesn’t know about. I always tell family members to the patient when they’re there with my patient, “I’m giving the naloxone too in addition to their opioid.” At that visit I say, “This is what I want you to look for. When I change the dose, I want you to wake the patient up at night, make sure that you can wake them up.” I’ll go through this list of things and give them a handout, give them a list of things of what it looks like, because patients don’t know. Family members don’t know what it looks like. They think they just die. Well, they don’t. They go through stages. And that’s predictable, so they can see it.

 There’s even a term attached to that: renarcotization. As you said, to add to that, [they’ll experiences] changes in skin color, a discernible slowing and breathing rate, and even abnormal snoring. Those are times before, while you’re getting ready or thinking you may need that to try to wake the patient to assess them. As you stated, after that first dose, during that continued observation, don’t let them go back to bed or fall back asleep. If you feel the need to call for EMS [emergency medical service], stay with the person, keep reassessing them, and debate the second or third dose if available.

I’ll say 2 other things. Look into their eyes. When you wake up from sleeping, your eyes should be dilated. If you look down and they are pinpoint, that’s not normal sleeping. Just about everybody can figure that out. The other thought is that many people are using multiple drugs when they’re overdosing. The most common are benzodiazepines and alcohol with opiates. It’s important to recognize that naloxone doesn’t reverse sedative overdose or alcohol overdose.

We have a drug that reverses called flumazenil. There’s a certain reluctance to not use flumazenil. Why? If you give too much of it, you precipitate a seizure from the benzodiazepine or potentially even the alcohol, so you can be in even bigger trouble. It’s very short acting, so you’re going to have to repeatedly give the flumazenil because benzodiazepines are very long acting. Sometimes the patient starts to come alive with the naloxone, but then they’re going back in. It may be the benzodiazepines. The only way you die from buprenorphine overdose, for example, is to mix a benzodiazepine with it. Even though you can’t die from an overdose with buprenorphine alone or a benzodiazepine—you could get run over by a bus, of course—the 2 of them together are lethal. [We need to] recognize that these are common combinations, and the FDA has recognized that with the new warnings for the benzodiazepines.

A group of specialists discuss overdoses and treatment with naloxone so family and caregivers are prepared for the future and for treatment.

Educating Family on Naloxone and Overdoses

 I’d like to point out something very important in this. We always think of fentanyl as a short-acting drug—quick on, quick off. But in fact, it’s not quick off for anyone who’s a chronic user because it’s very lipid soluble, so it goes into all the lipids and fatty tissues in you and slowly comes out. 

 meaning that the half-life of fentanyl when you give an acute dose and how long it’s going to last if you’ve been chronically using it are vastly different.

Naloxone is a very short-acting drug. We used to have the horror stories in the emergency departments. The intern would go in and give the 1 dose of naloxone. The heroin addict woke up and—well, they didn’t necessarily say thank you much because they were in withdrawal—and if you didn’t hook up the IV [intravenous] and repeatedly give the naloxone, they’d go back into an opiate overdose. It’s the same thing with fentanyl, and the bigger dose you give, it stays higher longer. You get a little extra bonus there, but the important thing is that you have to call 911, that you have to get the TMS [transcranial magnetic stimulation] people. You have to get the EMS [emergency medical services] people there because the 1 dose, even when you’re given a big dose, may not last long enough.

This is a critical lesson that we’re learning with these fentanyl overdoses when the EMS people get there and the person is back in an overdose. Even though they were given something that looked like it was reviving them, it doesn’t last long enough. The larger dosages that we’re going to need are repeat dosages with these chronic fentanyl abusers, not just 1 dose and you’re dead. I want to emphasize that. Of course, you’d like to not give so much naloxone that the patient gets into severe withdrawal. Because what they are going to be doing then is running away from you as fast as possible, so you don’t do that to them again. Nonetheless, it’s very hard to give too much naloxone.

Dr Kosten describes how to deal with a fentanyl overdose.

Pain Management

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