Thank you, AOHC Stalwarts, for hanging out to the very, very bitter end. We appreciate you being here, even though it's the last talk of the conference. I'm John Downs. For a few more months, military physician, background in internal medicine, occupational medicine and medical toxicology, but I'm here today just to introduce Jacob Formaga and Michael Holland. They're going to be talking to you about sort of flip thinking for bystander antidotes in the workplace. So there's the initial piece will be some anecdotes about a bystander antidote that used to be considered fairly commonplace in occupational medicine and still comes up occasionally, but we're hoping to discourage you from thinking about this one anymore and move beyond. And then Michael will be following with a not new, but newer antidote that we probably should be thinking about for use in the workplace in the current day and age. So Jacob is a emergency physician and medical toxicologist at UT Southwestern in Dallas. I found Jacob, though, because he is now medical director for occupational health at UT Southwestern there. He's becoming one of us, and we're very proud to have him. Dr. Holland is affiliated with SUNY Upstate Medical Center and the Upstate New York Poison Control Center. He's a professor up there, has boarded in emergency medicine, occupational medicine and medical toxicology. So he'll follow Jacob. Jacob. Thank you. So let me begin. Like everybody else, I have no conflicts of interest. For the first half of this presentation, we'll talk about the cyanide toxicity and the two antidotes, and then in the end, we will talk about which one to choose. So cyanide is considered one of the knockdown agents, and a lot of the movies and cartoons, whenever somebody's exposed to a toxin, they start becoming symptomatic and succumb pretty quickly. But believe it or not, there's only a handful of toxins out there that have such rapid effects. They're referred as knockdown agents, and cyanide is actually one of them. Because of how small of a dose you need in order to become toxic and potentially die, it's considered one of the agents of opportunity for terrorism. So small amounts can harm a lot of people. The video here on the right that I'm about to start playing soon is of Michael Marin, and in 2012, he was found guilty of arson and insurance fraud. He basically got in trouble financially and then burned down his house to claim the insurance money and was caught. So during the sentencing, which happened at about now, he, on this video, which was shown live on the news, was shown to swallow something, which later on was proven to be cyanide. And so initially, he's like, oh, I don't feel so well, can I have a napkin? And then when it was zoomed in, he suddenly started to have seizures and he died on live television. And so the reason why I show you this is this is how quickly it worked. He didn't even have time to get out of the courtroom. It just, it happened soon after he swallowed the tablet. So most of the cyanides these days, most of the exposures are from fires. So combustion of synthetic polymers, such as nylon or plastics, or even natural materials like wool and silk can produce hydrogen cyanide. It is also very lethal, 200 parts per million is sufficient to harm people, to kill. Cyanide is also a great oxidizing agent, so it's used in a lot of industries, such as chemical synthesis, tanning, metallurgy, printing, agriculture, even as fumigants and insecticides, even though a little bit less these days. So the way cyanide causes harm is it binds to the plus three iron, ferric iron, on the cytochrome oxidase. And cytochrome oxidase is one of the enzymes involved in oxidative phosphorylations, which we all remember as electron transport chain. So this is how most of our cells, well, how our cells make energy. And so when the cyanide binds, it prevents the electrons from jumping through the system to help make energy, and then it also prevents the electron from being used up by the oxygen. And so essentially with cyanide, our cells are unable to use oxygen. So functionally, it is the same as if there was no oxygen around. So not surprisingly, cyanide toxicity gives you symptoms as you would expect with hypoxia. And so the two organs that are most sensitive to hypoxia are brain and the heart. So this is why you get headache, confusion, weakness. You get seizures and loss of consciousness, which you guys saw on the video. But also you get dysrhythmias and cardiac arrest. So this is kind of a schematic of electron transport chain or oxidative phosphorylation. So the whole process happens on the inner mitochondrial membrane. And I just kind of wanted to show you this, so that way you can kind of visualize a little bit better the mechanism, so you can later on kind of remember the effects of it. So the cells, they drop off electrons using the NADH and FADH2. And every time the electron is dropped onto the cytochromes, they help pump hydrogen against the gradient. And as the electrons jump from one molecule to another, more hydrogens are pumped. And eventually this electron, again, is absorbed by, combines with hydrogen and makes water. So that's where oxygen is used for. Once the gradient is established, the hydrogens move down the gradient. And this is where the ATPase makes ATP, makes energy. And so when you have cyanide, it binds up with one of the cytochromes. And so as the electrons travel, they're suddenly blocked. And so they cannot be, jump onto the oxygen. And so once the electrons kind of accumulate, it's almost like a traffic jam. So no more hydrogens can be pumped and no more oxygen is made, no more energy is made by the cells. So overall cyanide, our bodies do have a natural ability to detoxify some of it, but as you can see, very low doses. So less than 0.02 milligrams of cyanide per kilogram per minute. So lethal dose is 200 milligrams can kill people. And even as low as 50 milligrams have been reported. So interestingly, one of the ways that the body is able to detoxify is through the methemoglobin. So methemoglobin is, again, another one of those molecules that we learn about. It's when hemoglobin, usually the iron is plus two on the hemoglobin. And the reason why it's plus two is because it's plus two, it's able to bind up oxygen, carbon dioxide, and carbon monoxide. But sometimes, and all of us have about 1% of methemoglobin in our bodies, which is iron that is actually plus three charge. And those are able to bind up negative anions, such as cyanide, even chloride, fluoride iodine. And so the way the methemoglobin does is it goes in and takes the cyanide away and frees up the electron transport chain. So there are external substances that are able to induce methemoglobin. So regular hemoglobin has iron plus two, which binds up the oxygen. But in the presence of nitrites, and again, these are present in the environment like well water and other locations, it can actually bind up and hydrogen, it can bind up the oxygens and steal the oxygens along with one of the shared electrons. So this is how you get iron plus three methemoglobin. So this property has actually been used in one of the first cyanide antidote kits called Lily Kit. You have hemoglobin, which then you administer somebody amyl nitrite and sodium nitrite to intentionally make methemoglobin in our bodies. This methemoglobin binds up cyanide. And then with another kind of component in this Lily Kit, sodium thiosulfate, it makes a compound that is then renally eliminated. So that's how you get rid of the cyanide in our bodies. So amyl nitrite is within the kit, is packaged in this glass ampule, which you're supposed to break, dispense the content of it onto a gauze or a handkerchief, and then inhale it for one minute at a time, and you do it three times. The idea is that you get enough exposure to then form methemoglobin in your body, which then binds up the cyanide, which then frees up the electron transport to do its job, make energy. So how well does it work? Studies show that you require about methemoglobin level between three and nine to have clinically significant beneficial effects when it comes to cyanide toxicity. So can amyl nitrite get us there? So in 1959, there was a study of six volunteers who inhaled 0.1 mLs of this amyl nitrite. And what they found is that when they measured their methemoglobin, their levels were between three and 6%, which is kind of in the region that we would see clinical benefit. However, there was another study done in 88, which showed three healthy volunteers who actually took the same amount as it is found in the amyl nitrite, one ampule container, and they inhaled it for much longer. But what they found is that at three minutes, their methemoglobin concentration was only 0.6%. Then at 10, it was 1.2. And then at 15 minutes, it was 2.1, way short of the recommended three to nine. So is amyl nitrite good enough? Nah, maybe. The other thing that you have to remember is that amyl nitrite does have side effects. So nitrites have side effects and it's difficult to titrate. People that don't inhale enough won't get enough of it and so won't produce enough methemoglobin and so will not benefit. But on another hand, those that are too vigorously inhale, they might experience more of the side effects that you would expect. So some of the side effects or problems with it is that it is very flammable. So it becomes a problem if you have these ampules in a non-hospital setting, and especially if those are present or if firefighters have them and close to a fire. You also have to be careful when storing them. They have to be refrigerated and kept away from the light because sunlight actually denatures the compound, so it stops being useful. Amyl nitrite also does have an abuse potential. On the streets, it's known as poppers. So diversion can be an issue, especially if you store those around your office or wherever you work. And then because of the nitrite, it can cause vasodilation, which decreases people's blood pressure. That and the fact that it makes methemoglobin, people that are sick that have low blood pressure and already are having trouble breathing because of low oxygen, this antidote might make things actually a little bit worse. So here comes antidote number two, hydroxycobalamin. So this is a manufactured pre-vitamin B12. It is injectable medicine given over 15 minutes. And initially it was marketed for macrocytic anemia. The side effects of this medicine are minimal. It just causes a little bit of skin discoloration and messes with pathologists' labs, but it really doesn't do anything too bad to the patients themselves. So in December of 2006, FDA approved hydroxycobalamin for the treatment of cyanide toxicity. And they marketed it as Cyanokit. It is kind of expensive. It's over $1,500 per vial. You have to store it at room temperature and it expires after three years. So many of the EMS systems, they can't afford to really put one into every single EMS break. So they usually bring it in the lead ambulance. So you kind of have to be careful with that. So the way hydroxycobalamin works is it's essentially the same as methemoglobin. It just binds up the cyanide and takes it away. And actually, interestingly, when it binds with cyanide, it forms cyanocobalamin, which is a scientific, which is named for vitamin B12. So again, the hydroxycobalamin is a pre-vitamin. It is, this benefits over the nitrite therapy is that it does not cause methemoglobin and it does not decrease people's blood pressure. So it is much safer for people that are really sick, that really need a cyanide antidote. So here's a table that compares the two antidotes. Amyl nitrite is great in that it works really quickly and it's really easy to administer because all you have to do is break the glass vial, dispense it on a handkerchief and start inhaling. The problem is that it's very variable about how well it works is depends on how you admit self-administer it. And it does cause methemoglobinemia and hypotension. Hydroxycobalamin on the other hand is a little harder to administer because it is an intravenous medication. So you have to start an IV before you can give it to somebody. It has a very rapid onset of action. It has very predictable effects and it does not have any of the toxicities of the amyl nitrite. So which one should you use? This is kind of the money slide because it says that in March of 2020, OSHA said, quote, amyl nitrite is no longer available in cyanide antidote kits in the U.S. and is no longer an acceptable initial therapeutic response. So which one do we use? Hydroxycobalamin. Any questions? We'll wait for just a minute at the end. We'll switch over for Mike, and maybe we'll take a moment for questions here. But I will say, part of the reason I asked Jacob to do this is, despite hydroxycobalamin being out for over 15 years now, it seems to be a recurring question amongst safety and health professionals that I have had a pretty significant back and forth with, even as recently as last summer, that they feel we have to have amyl nitrite on site if there is any potential for cyanide toxicity in a workplace. OSHA issued that letter of interpretation. There was, at one point, an appendix to, I believe, the acrylonitrile standard that mentioned using amyl nitrite, but it was never an enforceable thing. And so you may still run across folks who are in the related industry, metal plating or whatnot, that use cyanide, who, for whatever reason, may still be very adamant that amyl nitrite must be in the workplace. But that is somewhat archaic and old at this point. And if you talk to folks that were around when the Lilly kit was the primary antidote, I've not found one yet that ever said they had the amyl nitrite capsules around in the kits for very long. Workers found out that there's abuse potential, and they just went away. So this is why we would encourage, if you're in an industry that use that, please discuss with your local EMS, make them aware of this, and that if they get a call to your location, they should come with hydroxycobalamin, rather than depending upon the use of a vial of amyl nitrite. Do you want to take just a few minutes for questions for him, Mike, or do you want to roll? Yeah, sure. Okay. If there's just maybe one question, then we'll switch to Mike, and hopefully we'll have time. I see one in the back. Do you mind coming up? I hate to make you walk all the way up for a short question, but others can't hear, and I might not be able to either. I don't think there's any contraindication for you, for IO with cyanide kit, to my knowledge. Yeah, to my knowledge. No, it's been given, yeah. Yeah. It's fair with interosseous. Yeah. Yeah. To the bone. Yeah. Okay. Thank you, Jacob. Let me switch over here. Nice. Thank you. So Dr. Holland's going to talk to us about opioid antagonist sprays, and again, as recently as last summer when we were going through this, preparations for presenting talks for this year, Dr. Holland and I had a pretty contentious discussion with another physician in occupational medicine who was absolutely adamant that she did not want naloxone in her workplace, and so I felt with that that perhaps this was something we should bring up at AOHC to at least introduce, that if there were at least one person who was very adamantly against this, that perhaps we need to discuss it more amongst the group. So Dr. Holland, please. Well, thank you, John, and thank you for sticking it out. So I'm either the worst lecturer, and they saved me until the very end, the last thing, or I'm the best, and I'm batting cleanup. So let's go with cleanup. Kind of self-serving. There we go. Good job. From my wife, who's a librarian. Perfect. No charge. Perfect. All right. So Jacob told you about it. standard administered antidote that we should get rid of, and I'm here to tell you about one that everybody should have in every workplace, everywhere. So we need to bring it in. Okay. So Surgeon General says that's what we need to be doing, too. I mean, the HHS, Surgeon General, everybody agrees that this is what's needed. So why is this needed? So the scope of the problem, we all know there's an opioid overdose epidemic, and 2017 was a terrible year to show that actual, you know, number one cause of accidental death was car accidents in 2017, and opioid overdoses surpassed that. So the National Safety Council came out and noted that the risk of death for opioid overdoses exceeds falls, pedestrian incidents, drowning, and fire, and motor vehicle accidents. So it is a pervasive problem, and it's just getting worse. So this slide just shows you how males obviously outpace females, but the total, you can see just a rapid rise in the number of opioid deaths per 100,000 of standard population. And more updated figures, this shows, you know, the different deaths from drug overdoses, and you can see that rapid rise just in the last five to, actually eight to nine years was the synthetic opioids, and mostly fentanyl and fentanyl analogs. And so that's, I've highlighted that with the red arrow pointing to that line, and you can see how that one's just going rapidly going up, and it keeps going. So there's like been three waves of opioid epidemic. The first wave was prescription opioids, and that really started around, you know, 2000 or so, late 90s, 2000. A lot of that was from when the American Society of Pain Management said that, you know, people shouldn't be worried about, you know, opioid sleep disorders or sedation and respiratory depression because pain is a good antagonist, and we should be liberally giving opioids. But people were taking them and going to sleep, and, you know, while you're awake and you're taking the dose is one thing, but when you take the dose before you go to bed, that's quite another. And so the first wave of opioid overdoses, fatalities increase, was this blue one on the top there, but that kind of leveled off. And then the next wave was people that were addicted to opioids and started to turn to street drugs. So heroin, as you can see, in the late 2010, beginning around 2010 and into the 20-teens, it started rising. That's the red. And then so now because there's all these people seeking heroin, heroin had fentanyl added to it, and now fentanyl's everywhere, not just in street drugs. And so that's why that light blue is that astronomical rise in fentanyl overdose deaths. And you can see on there that in 2023, the fatalities peaked above 112,000. So, you know, in those other slides, it shows it was somewhere around 90,000, but now it's up to 112,000. And the latest statistics are someone dies from an opioid overdose every five minutes in the U.S. So, you know, 55-minute talk, 10 people are dying somewhere in the U.S. from an opioid overdose. And it's not just from street heroin or street drugs. Well, it's street drugs, but it's the DEA found that seven out of every 10 fake prescription pills seized had fentanyl in them. And they're very good. You can go online and look on the web about fake Xanax, and they look just like the real thing. And so people are buying them, thinking they're buying, you know, an anxiolytic, and they're buying something that has fentanyl. Most of the fake pills are distributed or they get to our supply by two different Mexican drug cartels. And they can look just like the Oxycontin or Oxycodone, Percocet, or Xanax. And I know there's personally a nephew of a friend of mine was at college, and he was anxious and he bought some over-the-counter, not over-the-counter, sorry, street Xanax that he thought was Xanax from a dealer, and it had fentanyl in them. And he was not opioid tolerant because he was just wanting a benzo, and he died. And so, I mean, it just happens to college kids. It happens to everybody, you know, all walks of life. It's not just some, you know, street bum or whatever, you know, derogatory term you want to be calling it. I mean, everybody that dies from an opioid overdose was somebody's lovely little baby boy or baby girl, you know, and most of them are their wonderful brothers and sisters, and many of them are fathers and mothers themselves. So, this is affecting everyone in the U.S., all walks of life, and it's a real tragedy. So, what do you do about it? Well, there's a perfect solution to it. Well, it's not a solution. It's one of the remedies, one of the tools that we need to be using is to save lives. And Naloxone is a great drug, and it's underutilized. You can see that's not just for people using heroin or street drugs. You can see here that cocaine is a street drug, but the black line is showing the red is with some opioids mixed into the cocaine that the buyer didn't understand was in it, and then many of them, the black is with synthetic fentanyl added to them. So, it's not just cocaine, but it's also in overdoses of street amphetamines or methamphetamine that people are getting, and they're mixing, the dealers or the producers are mixing fentanyl into virtually everything, tablets and injectable drugs. So, what do we do about it? Well, like I said, we have a perfect antidote. Just a little nerd bit about opioid receptors. There's three primary opioid receptors, and mu is the one we're mainly concerned about. The mu opioid receptor is what's responsible for, centrally, for the euphoria and analgesia for why these were originally prescribed, but the euphoria is that's with the high that they seek, but then also the respiratory depression, and as you use it more, you get more tolerant to the analgesia and euphoria, and so you have to keep giving higher doses. You do get somewhat tolerant to the respiratory depression, which is what kills you, but it's not complete, and no one gets complete tolerance to the respiratory depression, so you take enough, you can die from respiratory depression. In the peripheral tissues, it works as a, it has, the mu opioid receptors act on the bronchial smooth muscle as well as in the gastrointestinal tract, and that's why opioids work for cough suppressant and work for diarrhea, you know, so that's why you take these things for diarrhea because it slows things down in the gut as well as suppresses cough. And then kappa and delta are the other receptors, but primarily the mu receptor is what's active, and I just, you can't do a toxicology lecture without a structure, so I had to put a structure up there because that's what we nerds do, and which one is the red one? Is this one? Yep, that's the red. Okay. We're contractually obligated to include chemical structures in the electron transport chain. Exactly. So this is morphine, and morphine binds to the mu opioid receptor. It's almost a perfect ligand, and it binds well, and the reason we have opioid receptors, we have endorphins, endogenous morphine-like compounds that bind there and modulate your pain and other aspects, and so morphine binds very well there, and you can see the only difference is there's a hydroxyl group here, and the hydroxyl on this side is just a ketone, and then there's a small alkyl side chain here, and that's the only difference. So structurally, you can see they're so similar, but naloxone has a much more avid binding affinity to the receptor, so it can replace any of the opioids like morphine or heroin, which is diacetylmorphine, replaces them, displaces them off the mu opioid receptor, and then you start breathing again. So it's like the perfect drug, because I'm really dating myself by mentioning Lil Abner. Does everybody remember Lil Abner? And they said Kickapoo Joy Juice, it does something, and it doesn't do anything else. It's got real nice manners, you know. Well, this has really nice manners, because all it does is displace opioids from the mu opioid receptor, and it doesn't do anything else. So if somebody's not having an opioid overdose, you're not doing them any harm at all. You're giving them something that's not going to do anything to them. It's very safe, but it's very effective in reversing the effects. So in March of 2023, naloxone became over-the-counter. So you used to have to get a prescription before that, but it was easy to get the prescription, but people were hesitant to prescribe things, even though it's a safe thing, that were hesitant to prescribe people that they don't know. But we as addiction specialists were handing them out, just because anybody that has a high dose of opioid prescription should also have naloxone on hand. And if you have a family member that's on opioids, you should have naloxone on hand. But now everybody can buy it, because it got approved just a little over a year ago for over-the-counter use. And it was the first naloxone product approved for opioid use. Before that, you could see that the community distributions were going up, but they weren't nearly enough. And the HHS determined that they just weren't enough for the amount that was prescribed of opioids. There wasn't enough naloxone being prescribed. So that was one of the pushes to get it approved for over-the-counter use. So now that it's over-the-counter, anybody can get it. But before that, health care providers and EMS services, community-based overdose and drug treatment clinics, police and first responders, and pharmacies. And so pharmacies were encouraging it on people that were getting opioids filled. So the CDC guidelines for prescribing opioids and chronic pain, and recommendations for having naloxone either co-prescribed before it was over-the-counter, but now recommended in having it. So you should have it to anybody that has an increased risk of an opioid overdose. And that would be patients who obviously had a prior history of an overdose, anybody who's taking drugs that has a substance use disorder, anybody, even if they don't have a substance use disorder, if they're taking a morphine milligram equivalent, that's the MME, of greater than 50 milligrams a day. Because that places them at a much higher risk. Two to three fold in somebody's above that of the risk of an opioid overdose. And then somebody who's any dose of opioids, if they're also prescribed other respiratory depressants like benzodiazepines, because they act synergistically, or at least additively, in respiratory depression. So HHS has these guidelines, which I just said, about somebody who's had substance use or had previous overdose. But also, any dose of opioids, if they have some sort of a breathing disorder like COPD or obstructive sleep apnea, because those people are at a much higher risk of going apneic when they're asleep with a normal opioid dose that may not be lethal if it's during waking hours. So you have to be careful with that. And then again, anybody that was co-prescribed any other respiratory depressants or heavy alcohol use, because that is a respiratory depressant as well. It's a sedative drug. And interestingly, anybody that's gone through a treatment program or has been incarcerated, they're not getting their opioids that they normally take. And so it just takes a week or around that to become no longer tolerant. And so if people go back to using the same dose that they used before they, you know, went into withdrawal, they can suffer respiratory depression if they go back to the same dose that they took when they were tolerant and they are no longer opioid tolerant and they're opioid naive. Prior to going over-the-counter, there was only one time every 70 high-dose prescriptions dispensed were also dispensed a naloxone. So it was very underutilized when it was a prescription medicine. And here's just a graph showing those are the ones that got high-dose prescriptions with naloxone, and those are the ones that get high-dose prescriptions and no naloxone. So it was just underutilized. So hopefully going over-the-counter will change this. So it's just a picture of it, and John, this is the nice little box it comes in. So what does an opioid overdose look like? So mainly you're looking at somebody who's unresponsive and respiratory depression. Very slow respirations or uneven or periods of apnea or completely apneic, not breathing at all. Or snoring, gasping respirations, gurgling sounds, those are people trying to, you know, they're total body relaxation and so their pharynx is all floppy and their respiratory efforts are maybe just gurgling or snoring or very slow. And obviously, signs of hypoxia, cyanosis. Pinpoint pupils are typical of opioids for the pupillary response. And then, of course, they can be bradycardic and pale complexion. So these are things that you tell bystanders because we're trying to push this in the workplace. So it's not just for your medical department. It's anybody. You know, these need to be available just like an AED is available and, you know, bag valve mask and all those things should be available to anyone in the workplace. So what is the bystander supposed to do? So you maintain a clear airway just like you would with someone maybe who's having, you know, vomiting or a seizure or whatever. You roll them on their side and make sure their airway is clear. And you can provide respirations if you have availability of bag valve mask and then administer the naloxone. And the great thing about it is you don't need an IV. You know, these things that you saw the picture, it's just a little nasal spray and you just there's instructions. Peel it open, put your fingers on it, put it in the guy's nostril, and you just pump it. And John's going to open it up. And it's relatively cheap. You can buy a two-pack at Walmart. There it is. You just peel it open. It's a little thing. You know, it's pretty idiot-proof because, you know, you just your fingers are on it and it goes in the nose. Thank you. It's only about $40 for a two-pack. So you get two of these. Is there two in there? Yeah, there's two in there. So you get a two-pack. So it's 20 bucks each dose. Any workplace can afford that. And then there's a new kid at the dance now. There's a nalbafine. Op-V is the brand name. It's the newest edition. You notice it's a longer-acting, it's also a pure opioid antagonist, but it's much longer half-life. So naloxone has a half-life of, you know, 20 to 40 minutes. But nalbafine has 10.8 hours, a half-life. It's only prescription now, but it's a similar cost. It costs about 40 bucks per dose. This is 40 for two doses. So the cost is the same, but it's still prescription only. And you can see it's virtually identical, the same, you use it the same way. That's nalbafine, brand name Op-V. And I'm not, I don't have any relationship. I'm just telling you that that's the next one. That was just approved by the FDA. So what is the complication? So if somebody is not opioid overdosed and you accidentally gave them that because maybe they had too much alcohol and they had too much benzos and they're having respiratory depression, you're not going to harm them by giving them naloxone. But when someone who's heavily opioid dependent, if you give them naloxone, you're going to precipitate somewhat, you're going to precipitate withdrawal. Now, we also use this term called precipitous withdrawal, and that would be if somebody's opioid dependent and you give them a big dose of IV naloxone, you will completely displace all opioids and they will go in, you know, you will precipitate a bad withdrawal. And those people can get very anxious, irritable, combative, and it's not pleasant at all. The nice thing about the administration of naloxone intranasally, it's pretty fast onset, but it's not fast like IV. So it kind of like slowly, so these people start to wake up, first thing they do is they start breathing again, and then they may wake up, but it doesn't really precipitate a terrible combative withdrawal. So it's really nice compared to, you know, precipitating it with an IV dose. So what does withdrawal look like? So remember I told you about the slowing down the GI tract and when you're opioid given, you know, stimulating the immune opioid receptors. So when you precipitate withdrawal, you're going to get, you know, agitation, nausea, their GI tract starts to wake up. They can get diarrhea, vomiting, then they get the goose flesh, tearing and runny nose, and yawning is a very, very commonly described things. The main thing, those things are maybe unpleasant, but the really bad precipitated withdrawal is, you know, they can get very irritable, anxious, and agitated. So those are ones sometimes you're going to need to have to restrain the patient, but usually it's not as bad as the IV, and I've not had anybody really report bad precipitated withdrawal with using the intranasal. But it's shorter half-life is really beneficial because somebody gets really uncomfortable and bad and they're anxious and really combative, it's going to go away because it only has a short half-life and their opioids that they took are probably longer half-life, and so they're going to get resedated. So obviously you don't give somebody naloxone and then let them go home because they're, you know, their opioids still on board, but they'll feel better because the half-life is short and it'll start to wear off. That's not so with nalbafine. Nalbafine has a much higher, much longer half-life, and when they get into withdrawal, they're going to be in withdrawal for 10 hours, theoretically, because it has a long half-life. So the American Academy of Clinical Toxicology and the American College of Medical Toxicology, that's our two group of nerds, came out with a position statement just last year recommending that this precipitated withdrawal and the prolonged withdrawal that's induced by nalbafine is not well studied and not tested in the field like naloxone is, and so our recommendation right now is that you should not have the nalbafine replacing your supply and go with the over-the-counter naloxone for your antidote to stock. And so remember, the people that have opioid addiction are your neighbors. You could be sitting next to people in any community setting, social setting, this setting, that's opioid addicted. So anybody that's had a prior overdose or anybody that's on a morphine milligram equivalent, more than 50 milligrams a day, or has some breathing disorders or sleep apnea or COPD that's taking opioids or taking opioids with alcohol or with benzos or other respiratory depressants, these people should have family members and other people know that they're on this and somebody should have naloxone. So that's why my plea is that we should have this, you know, we have it in, like John's wife is a school librarian and they have it in the schools. Public librarian. Public librarian. Okay, so, and school nurses have them most places. It needs to be everywhere because it really does save life. It doesn't stop opioid addiction, but it saves someone from dying from opioid that can then get into treatment and become, you know, recovery. So I plead with everyone that this should be in the armamentarium of every occupational medicine practice and employee health service and occupational health clinic. Okay? Thanks, Mike. A couple of things on this real quick just for personal comments. So if you all are familiar working like in an emergency department, Mike talked about intravenous dosing of naloxone. That's usually a 0.4 milligram dose. These are four milligram in the little atomizer here. Really because you're going to put this up the nose and try to get it to cross across the capillary membranes there. So you're probably going to lose some of the drug just by dribbling out of the nose. So you're going to need it. That's why the dosage is a bit higher here. The other thing is when we give intravenous naloxone, as Mike said, that's a very like quick rapid response within a matter of seconds usually because we're giving it right into the vascular space. This is going to take a bit longer. So I don't want to overlook that before there was such thing as naloxone, there still was a way to save people from an opioid overdose. What was that? Yeah, we can give rescue breathing, give breaths. So you may not feel comfortable with that. I assume that most folks, emergency response kits, AEDs and whatnot have some sort of barrier valve in there for you. But while somebody else is getting naloxone, if they don't have it in there, if this is a person that's looking pale and blue and doesn't have adequate respirations, if they don't have a pulse, then we've got to start CPR, but if they still have a pulse and they're not breathing, time is brain in that regard. Don't let them be hypoxic. And also because this is being shot up into the nose and we're having to go through the process of it getting across the capillary membranes, it takes a bit longer. So it could be as much as a few minutes as compared to relatively rapid seconds onset with IV. So again, if you're seeing someone or you're training in your workplaces, and I hope that you all are, about using this, just please remind them that this isn't rapid onset. You still need to help protect that person's airway, give them rescue breaths as needed until this begins to work and start coming around, because the kinetics on this aren't the same as with intravenous dosing. And again, my wife is a public librarian in Chesterfield County around Richmond, Virginia, and they now hand these out to anyone that comes into their library, no questions asked. I'm not here pushing for Narcan as a trade name, but this is labeled right on the box, not for resale, not for retail. So this is given out by the county, along actually now with fentanyl test strips and xylosine test strips and benzo test strips to anyone that wants to come in. So if my wife as a librarian can do that for folks, I think we should feel comfortable doing it in workplaces, particularly if we've already been comfortable being the medical director for the AED program or emergency response or whatever. And so I'll shut up now, but the last thing I'll say, so I'm not really shutting up, is just as a show of hands, how many folks know if you have naloxone in like emergency response kits already? Is it in there with? Okay, so you got about half and half, okay. So kudos to one half, and then if you didn't raise your hand, then I encourage you to go back and think about how you're going to make that happen, because I believe it's only a matter of time. We've had AEDs in workplaces for years on the contingent that maybe someday someone will have a cardiac arrest and that will help. This is sort of the same principle. Questions about either? So you saw the CISCO nurses raising their hands, because recently we, even though it's over the counter, we put it as a standing order with our medical oversight group. That's 20 sites. We have over 170 sites at CISCO. How do you recommend, is there like a rollout kit online you can find for non-medical people that can do this easily? What is your recommendation for rolling out? Yeah, so the manufacturer, when it went over the counter, you click on the website and there's a little video to show you how to do it and the little short training thing and the graphics and stuff like that, and it's available to anyone. So even though you can Google it, we had to put together training for our nurses, a standing order. You can't just tell 150 sites, Google it. No, right. Is there a quick and easy implementation procedure maybe that they've already created for non-medical sites to hand out, train on and go? Yeah, I mean you can send the link to Narcan's website that has the training video on it, so you don't have to Google it. You could, you know, on an email you could send the link right to it, and this is the training video. Click here and train them that way. Are you asking more of a logistic question or? Do you have to kind of create the procedure for people at sites? Yeah. Sure. I guess you're like, is your question, do you think there still should be a medical direction document even though this is over the counter, same as there's a medical direction document for the use of the AED and then the rollout or phase out of that? Yeah. But, you know, you could create your own packet, a printed packet, too, from, you know, printing those instructions, but I think a link would be easier, like when you go to an email, but for, like, for a standing order, I mean, even though aspirin's over the counter and acetaminophen is, you still have, for an on-site clinic, you still have to have a standing order for it. So, yeah, I think you would probably have to do that, too. I don't have a quick answer for that one, or I haven't seen that. That's a good, perhaps a good thing for some of us to work on as a standard template for Naloxone administration in the workplace, the medical directorship for that. Yeah. Thank you. All right. Going once, going twice, do I declare AOHC over and everyone to go? To go home?

bystander antidotes

cyanide toxicity

Amyl Nitrite

Hydroxycobalamin

opioid antidotes

Naloxone

workplace safety

emergency response kits