Good afternoon, everyone. My name is Allie Vick, and I'm here to welcome you to the Management of Stimulant Use Disorder Guidelines Intoxication and Withdrawal Webinar. Again, Allie Vick with the American Society of Addiction Medicine. Today, you will be hearing from Dr. Timothy Wiegand. Before I turn things over to Dr. Wiegand, I'm going to go over some logistics and announcements with you all. Dr. Wiegand, if you would go to the next slide, please. So this webinar is brought to you through a collaboration through ASAM and AAAP. Next slide, Dr. Wiegand. AAAP is a national professional society that focuses on evidence-based prevention, treatment, and recovery approaches. ASAM, founded in 1954, is a professional medical society representing over 7,000 physicians, clinicians, and associated professionals in the field of addiction medicine. So ASAM, we're very grateful to be working with AAAP on this project. Next slide. So we are going to begin our session with some brief announcements about how to use the Zoom features. So please note, as an attendee today, you are set to mute. There will be time for you all to ask questions throughout the presentation. You may do so using the Q&A function through Zoom. You should be able to see this. The chat, you are able to chat with panelists and hosts. If you have any technical questions, please use the chat feature throughout today's webinar, and someone from ASAM will be able to assist you. So again, today's webinar does have the opportunity, you do have the opportunity to ask questions. There are some ground rules. Take time to understand the cases and participate actively. You also will have Zoom polls throughout today's presentation. We ask that you do participate in those polls. Embrace diverse experiences. Assume positive intentions of your co-participants. Monitor your participation and do seek clarification respectfully. I am now here to turn it over to Dr. Wiegand. Thank you all for being here. Thank you, Allie, and thank you, Dawn. I want to also thank the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry. I think this is an outstanding project and I'm very pleased to have been part of it. I'm Tim Wiegand, Director of Addiction Medicine and the Addiction Toxicology Council Service, Program Director of URMC Medical Toxicology Fellowship and the Addiction Medicine Fellowship in Rochester, New York at the University of Rochester. And I'm also the Treasurer of the American Society of Addiction Medicine. My background is in medical toxicology and addiction medicine and practice on the interface. Today's objectives, we're going to go over the guidelines recommendations regarding the management of stimulant intoxication and withdrawal or discontinuation. We'll look at acute complications associated with intoxication and how to address them. The workup of patients, the evaluation by level of care, and when to determine patient needs higher level of care or appropriate treatment can be done where you're at. And then we'll apply the knowledge that we've gained to a case of stimulant intoxication using case-based scenario. And there is going to be opportunity at the end for questions. Please use the Q&A and there will be poll questions inserted throughout. Again, agenda key guideline recommendations, go over some management of acute complications, and then we have the case illustration. So focus on intoxication and withdrawal and identification of complications and how to address them. As a toxicologist and pharmacologist, drug delivery to the brain is really, to me, the underlying basis of addiction medicine. You need to get to the brain to elicit response. More rapidly the drugs reach the site of action, the greater the reinforcement. And so that drug route of administration plays a great deal of importance in terms of the effects of the drug, not just the euphoria, smoke versus IV versus oral, but also toxicity can depend on route of administration as well. And we'll talk a little bit about that. It's obviously important in identifying not just the toxicity from the drugs, but there can be particular effects due to route of administration as well. And we could spend hours going over just simply one particular type of stimulant and all the nuances when I can get to that level of detail in this webinar. But just understanding that changes to route and dose can lead to different effects, not just euphoria, but toxicity. This is a picture of Paracelsus, and this can summarize toxicology in one simple sentence, and that's the dose makes the poison. And I think when you're talking about any toxic effect stimulant, toxicity in particular, the dose makes the poison. The route makes the poison as well. And then as you'll learn, some particular drugs have nuanced effects as well. Paracelsus was an academic philosopher, a very interesting individual that lived in the 15th and 16th century. What are stimulants? When you think of stimulants, you probably think methamphetamine is common. There's a lot of variation depending on where you are in the country. In the primary stimulants, methamphetamine or cocaine are probably two most common. We also have amphetamine and prescription stimulants. Methamphetamine is available via prescription cocaine as well in certain situations, but mostly illicit. We have methylphenidate or Ritalin. We have lisdexamphetamine, a prodrug that turns into dexamphetamine as a stimulant. We have bupropion. Sometimes people don't think of bupropion as a stimulant as well, but as a backbone is phenethylamine. It can trigger false positive amphetamine and delivers reward in particular if it's crushed or insufflated or injected as well. We have some of the synthetic stimulants, MDMA, cathinones, otherwise sometimes called bath salts, a host of designer stimulants that we won't cover completely here. Some are really important in terms of potency and misrepresentation. The n-bomb, n-benzo-ortho-methoxy, phenethylamines that were misrepresented as LSD or sold as fake or synthetic LSD caused a lot of problems in individuals expecting hallucinations. They got a severe sympathomimetic experience instead. A lot of different types of stimulants out there. We'll talk about some of the basics. Talk a little bit about route of administration and different effects. I think this is important to look at the main routes of administration. This is a picture of different routes that drugs can come in the system. We have sublingual. Think of sublingual films. They bypass first-pass metabolism. We have oral, simply chewed, swallowed. There's some absorption already occurring maybe in the nucleus membranes. We have intranasal, which bypasses the first-pass metabolism as well. It's breakdown through the gut, breakdown through the liver. For some drugs, this is really important. It's also important in terms of how quickly the drug is getting into the system. Again, the route of administration could have particular effects in terms of toxicity. You've all heard of perforations to the nasal septum for individuals that are persistently using large amounts of cocaine. Cocaine has that local anesthetic effect. Basic constrictions, you can get perforation of the nasal septum and complications to the nasal pharynx. Inhalational through the lungs, toxic effects from adulterants as well as the stimulants themselves can cause hemorrhage or inflammation, pulmonary edema. Rectal administration, somebody that normally takes a medication or a pill by mouth and hears that you can get a higher concentration by administering it rectally, bypassing the liver's metabolism, may try inserting an MDMA tablet rectally. This can have really important implications down the line. Stimulant use is associated with a lot of impulsive behavior. I'll be talking about chemsex at an upcoming webinar. Insertion of any medication or drug rectally and then unprotected sex is a much greater risk of sexually transmitted infections, so opportunity for counseling patients. Again, considering effect and toxicity and nuances by route of administration. This is a graph of cocaine concentration by route of administration over time. And you look at the Cmax or the highest concentration that the drug achieves is quickest for, actually it's hard to see, but it's quickest for smoke compared to IV. And then as you drop the concentration and it moves a little bit to the right, the delay to Cmax occurs as you change from smoked IV to nasal, to oral, to transdermal. Transdermal is not up there. This has important implications in terms of the euphoria. As I mentioned earlier, the quicker the drug reaches the reward circuit to the brain, the more euphoric that individual experiences the drug. And this is a graph of cocaine subjective high by route of administration. And you can see that you could almost overlay this graph of peak concentration in time by subjective high. So people are more likely to use a drug by a particular route if they're pursuing that euphoria, which is what most of our patients are pursuing. Not in all cases. And then considering that at least nuances by that route of administration like pulmonary, really important to get a good lung exam, counsel the patient about inflammation, adulterants that can get into the lungs, IV, looking for sites of infection, cellulitis, bloodborne infections. So counseling by route of administration, really important to already give the rectal exam example earlier. All right, so initial assessment of a patient where you're concerned for stimulant intoxication, you want to identify things that would indicate the patient needs a higher level of care. Certainly looking at the patient, is there something that's going to kill them? I see a lot of patients in the ED. We talked about the ABCs, airway, breathing, circulation. Most of our patients with stimulant intoxication are going to be breathing, their airway should be intact. That's not always the case in today's world of fentanyl adulteration. We'll talk a little bit more about some additional opportunities, harm reduction, fentanyl testing in particular in stimulant users with cocaine. There's also a lot of concomitant fentanyl use in our stimulant users. So airway, breathing, circulation is very important. There may be other drugs involved. Exams should really consist of a clinical interview. Not everybody is going to be able to participate in a clinical interview. And this is really important in your initial approach to someone who's intoxicated. We don't automatically reach for the first medication to knock someone out, for example. We want to try and talk to somebody, deescalate, get them to a calm environment. And for many individuals, that works well. Stimulants are excitatory. People that have been up for a while are anxious and agitated. They haven't been sleeping can be psychotic. They can be paranoid. That's very difficult to get a good exam and to deescalate and to figure out, am I going to be able to deescalate and talk to someone or is this heading in the wrong direction? That's really important to be able to do, to appropriately do quickly. A physical examination is critical. And you get a lot just looking at someone quickly and closely, although looking at the skin is very important for somebody who's using IV, getting a good detailed skin exam, looking at the groin, for example, maybe somebody's injecting in the groin, the neck, in parts of the country. So not all exam is certainly quick and from across room, but how someone's walking. Are they relaxed? Are they pacing? Are they taking off their shirt and flushed and beet red and just drenched sweating? Are their pupils extremely dilated? Really important. It's important to get the self-report of the patient. What happened? To the extent that they're able to provide it. Tell me, do you know what you used? Sometimes people think they used something and it was another thing. I hear a lot of patients say that they use Molly and they're convinced that they use 100% pure MDMA. And really what Molly is just kind of another slang for some white powder crushed up as a bunch of stimulants. Often now the old cathinones or bath salts. Could be MDMA, but oftentimes other stimulants as well. Collateral information is important. Is this individual just taking the stimulant or is it, have they been on a binge? Any trauma associated with this other behaviors? What was the context? And then obviously an assessment for individual risks to themselves or to others. Suicidal, homicidal risk, really important to get help very quickly. Depending on your level of care, that might not be readily available to maybe calling for quick escalation to level of care. Stimulant intoxication is caused by a combination of excitatory neurotransmitters. And this isn't comprehensive, but the main ones being norepinephrine, serotonin, dopamine, these are excitatory neurotransmitters. I like to think of stimulant intoxication as a fire. And I'll talk a little bit more about that. You can certainly have a mild, moderate, severe fire. Some examples, again, cocaine, methamphetamine, amphetamine, bupropion, MDMA, methadone, MDPV. These drugs cause excitatory effects through the increase in catecholamines, increase in norepinephrine. Think of the fight or flight response. Your heart rate goes up. Blood pressure goes up. Blood pressure is shunted to the muscles. The temperature goes up because of the muscular activity. Pupils are dilated through the alpha one effects of norepinephrine. Sweating occurs because of the temperature. Sometimes the increased muscle effects, but also some of the stimulants have direct effects in the brain, centrally at raising the temperature. There's psychomotor agitation. People are moving around and can't stop fidgeting. That all causes energy expenditure, sweating, dehydration, muscle breakdown and turnover depending on the severity. So our labs may determine, what we're doing for labs may be based on the degree of intoxication. Often people that are under the influence of a stimulant have tremor. Some stimulants are also serotonergic, and you can see serotonin toxicity. Serotonin toxicity can have tone that's increased in particular in the lower extremities to the point where patients are rigid. And that's really important to notice whether they're not able to walk because of maybe an injury or because they're completely stiff in their lower extremities and you need to give them some medication to relax that neuromuscular excitability. It's important to consider signs of trauma. In a case last night, a patient intoxicated with alcohol and stimulants and concern for trauma because of a fall and a co-ingestion to do some workup for trauma. The volume status, meaning their hydration level is really important. Dehydration can cause a variety of complications in particular in the kidneys. Mental status, as the temperature goes up, our way of cooling is through evaporative heat losses. Patients get dehydrated, really bad complications can occur from electrolyte, metabolic, toxic, and end-organ effect. And it's really important to determine whether or not someone's agitated or intoxicated, anxious, and agitated versus psychotic. And then at the same time, we need to rule out other concerning or life-threatening causes that mimic stimulant intoxication. Some of these are really concerning and need to have a very quick workup, meningitis, encephalitis, hypoglycemia, someone that's agitated and combative and seen by medics, pre-hospital and community, they'll have a glucose check right on scene. Alcohol or sedative withdrawal is very similar to stimulant intoxication, benzodiazepine withdrawal, serotonin syndrome toxicity, the type of stimulant toxicity, but that can occur with other drugs that are not stimulants in and of themselves. Some endocrine, theospromocytoma, psychotic state, head injury, traumatic head injury, and a host of other things. Some of these things, not all of these things need to be assessed for depending on some collateral information. A patient may come to clinic and say they just took a double dose of amphetamine. You notice that they're a little sweaty and a little tremulous and you have a discussion about the use of amphetamine. You don't have to rule out hypoglycemia or meningitis or all of these other things, but just having that discussion, that collateral information is very important. I use this, put out the fire in lectures that I give on withdrawal. It's really the same thing when we have patients with stimulant intoxication. Stimulant intoxication is an excitatory state. An excitatory state, we need to deescalate the excitation. We do that through raising levels of inhibitory neurotransmitters or blunting the effects of excitatory neurotransmitters. This is just think of as putting out the fire. If you think of putting out the fire, you have mild fires, you have moderate fires, you have severe fires. Your reaction to this should be based on the degree of fire, the degree of intoxication, real mild effects. You may be able to put out very easily at a lower level of care without using parenteral or intramuscular medications or even using any medications at all, just kind of let it run its course. If the patient is able to maintain their hydration, they're getting rest, they're not psychotic, they're not paranoid. An individual that has been on a methamphetamine binge or swallowed a bunch of methamphetamine or cocaine to avoid police detection may have a really abrupt onset, bag ruptures or something, and really need acute, intense intervention to avoid really catastrophic outcomes. So you need to gauge your treatment on the individual patient's level of intoxication or how much the fire is there. A little bit about toxicology testing. A lot of people ask, let's test for what are the toxicology sending, let's send out for the toxicology testing. Most toxicology testing is, in this context, going to be forensic or in the setting of clinical addiction, medicine is going to have some use versus the emergency department, other use. Most of our treatment in the emergency department, we're treating the patient with acute severe stimulant intoxication well before we have any toxicology testing back. And there are many substances that I'm not going to be able to test for in the emergency department. Certainly there are designer stimulant panels and you can send out things, again, more for forensic information. I think really important now in the era of drug surveillance is the drug supply has gotten more dangerous and adulterated. It's really important to understand what's in the drugs as well as what's in the individuals. But for what you're doing clinically for the patient right in front of you, toxicology testing is going to have less implications and less importance than it would for surveillance, forensics, and for clinical addiction medicine potentially determining how well somebody might be doing with terms of relapse use. And again, not going to be the only thing that you're basing decisions on. There are some situations. I have in the Southeast, there are certain bites. The scorpion envenomation can look just like methamphetamine intoxication. I have colleagues working in Phoenix where a toddler comes in, looks like methamphetamine intoxication may have been an accidental ingestion. Or they were told by the family that they got bit by a scorpion and the testing shows that methamphetamine is present. So there may be some times where you're able to more quickly address or adjust your care or at least what additional steps you take, at least in evaluating the house for safety, things like that, family, more questions, but some limitations. All right, your assessment, the observation, exam, interview, a little bit more detailed assessment. The mental status. Mental status is important. If someone agitated, are you still able to have a coherent, well, a relatively coherent discussion with the patient or are they often left feel paranoid talking about things that aren't there, attending to external stimuli, picking at the skin so that they, because they think that stuff is crawling under the skin to the point where they feel like there's formication. That's really important. Or is it just that they're really agitated and they're angry and you can talk to them coherently and that's a great opportunity to try and be a calming presence, deescalate, not antagonize, limit other intervention. Skin color, presence of sweat, really important. Is the patient flushed, bright red, are they sweating? It's really important to find out if they're sweating, but it's really limited just to kind of under the skin, they're really, really warm, but I can only feel the sweat, the nexilla under the back. I better get a core temperature in that individual if they've been particularly intoxicated for a period of time, that may be somebody getting really dehydrated and their ability to cool is going down. I got to make sure I hydrate that individual. Urine output, muscle tone, muscle tone, important, already mentioned is a tone stiff to the insert tone and toxicity, or they just have kind of psychomotor agitation, they're moving around, looking at muscles and joints and the skin for signs of trauma, in particular with methamphetamine use, a lot of trauma patients in areas of the country coming in with methamphetamine use stimulants in particular associated with higher rates of trauma than other drugs, alcohol certainly very common, but stimulants are as well. Skin injury, sometimes patients that are using stimulants are picking excoriations, it's a sensitization effect, repetitive action that occurs while they're using the stimulant to give distorted reward response. You've all seen patients that have been using cocaine and come in with picking and scabs and things like that. Skin injury and cellulitis, abscess if somebody's using IV, intravenously really important as well. I already talked a little bit about musculoskeletal injury and trauma. Breathing pattern effort is very important, in particular if you have a severe intoxication, that's one of the ways that we compensate for acidosis. If you have the more severe level of agitation to the point where the patient's hyperthermic, they have a lot of muscle breakdown, they have a lot of lactic acid, their pH is dropping, that breathing off of the CO2 is really critical. This is really only in the more severe intoxications, but that's really important to recognize that. You got to cool that patient and check the potassium, get some labs in, treat that individual with sedatives very, very quickly. Breathing pattern, respiratory exam, really important if someone's smoking drugs. I've had everything from pneumonitis, hemorrhagic pneumonitis, pulmonary edema, pneumothorax with free-based cocaine. Patients are taking a deep breath, valsalva down, they pop a blub in the lung, and now they've got subcutaneous emphysema, pneumothorax, or pneumomedius thymum. I can remember a chest x-ray very vividly that I saw in residency at Pennapin County Medical Center. One of the pulmonologists explained how tall males in particular were at increased risk for pneumothorax when they smoked drugs. Always asking about smoking drugs when you saw someone come in with a pneumothorax in the right context is really important for the history. Respiratory analysis can depend on level of intoxication, level of care. The individual that's coming into a detoxification unit or an inpatient setting that maybe had an extra amphetamine and there's mild effects that are wearing off that are able to hydrate, you may not need to get any initial labs. It may be part of the protocol or workup, but that may not be related necessarily to the intoxication. In general, if someone's coming to the emergency department and it's moderate to severe stimulant intoxication or has been on a binge, a CBC, that may be important for cocaine use, how much they are showing signs of vasculitis that sometimes occur with the adulterant levanosyl that can cause neutropenia. BMP, basic metabolic panel looking at the potassium in someone that's had high temperatures, acidosis, muscle breakdown, looking at the kidney function if they've been on a binge or cocaine, adulterated fentanyl, prolonged downtime, comes into the hospital, fortunate makes it to the hospital, we find out that they normally are using cocaine, something very different happening, you suspect it's fentanyl, checking the kidney function, also checking the CK for rhabdomyolysis that could be a mild globular renal failure. CMP is comprehensive metabolic panel, that also includes the liver function, transaminase levels, the glucose is also part of the BMP, liver function may be important. Depending on route of use, some individuals may have hepatitis, hep C, some drugs can have hepatotoxicity, hypoxia, hypothermia can affect the liver. CK, creatine kinase is a marker of muscle injury as is AST, so the AST may be elevated with CK with a lot of muscle injury. A lactate may be important if there's an anion gap on your chemistry, that lactate may be elevated in a situation of sepsis or hypoxia, or just that prolonged muscle hyperactivity and temperature elevation, and that's very concerning. You want to find the source of it and stop serotonin toxicity can also cause lactate elevation. And then cardiac biomarkers may be important in cases of chest pain, EKG changes, extreme tachycardia, demand ischemia, and obviously treatment of that very important. Not all chest pain is due to the heart, certainly in stimulant intoxication, musculoskeletal, panic, lung, a lot of other causes as well. A trauma, I already mentioned musculoskeletal, real important as well. Other evaluation, EKG, evaluation of trauma associated with intoxication, imaging of signs of trauma, so getting that collateral information may be important. Testing for sexually transmitted infections, so I'm going to be, as I mentioned, have a coming webinar addiction toxicology case conference where we're focusing on chem sex and the drugs involved, toxicity, opportunities for harm reduction, prevention. So again, route of administration, really important. Screening for SDIs may be really important depending on individual use and collateral information. Setting determination recommendations. Patients with stimulant intoxication are usually managing acute care settings, but many can be managed in lower acute clinical settings if they're cooperative, if they're responsive to interventions, they de-escalate with verbal and nonverbal de-escalation strategies. Maybe you need some medication, you have those medications on site, you're able to give an oral dose of an olanzapine to someone that's been up for a couple days to get them to calm and rest, or give some oral isopam for excitatory effects that need to kind of calm down, mild hyperadrenergic stimulant. Symptoms and signs can be very responsive to even low doses of medications as long as there's not ongoing use or you need to also assess, reassess trajectory of intoxication. Clinicians need to be able to assess for other acute issues and complications, monitor vital signs or at least check them initially, and then again monitor risk of self-harm or risk of harm to others. One of the levels of care that I cover, I get a lot of patients transferred from an emergency psychiatric facility fairly quickly, cleared after suicidality and homicidality, that can be a very dangerous situation, depending on how careful of an assessment occurred. Our healthcare system is fragile in many places, and unfortunately some of these patients, it's like hot potato. It's okay, there's a level of care I can get this patient to that's safe, and sometimes there's a misunderstanding on what level of addiction care is able to provide. I find that all the time, that a hospital believes that patients can be given fluids intravenously or treat very aggressively with medication escalation, don't understand the nursing to patient ratios, for example, that you need, or whether or not security is on site, so having some of that understanding if you're at a level of care and accepting a patient is really important. Are you able to provide hydration? Not all hydration needs to occur intravenously. Is the patient able to drink? If I'm looking at somebody, even if they tell me that they've been on a binge, haven't been sleeping for days, but they're coherent, they just want to go and rest, they're hungry, I ask them, have you been able to pee? They maybe haven't, but then they're trying to drink some water or whatever fluids we have available, and then they'll come back and I'll say, what color was your pee? Were you able to pee a little, a lot? And if they say hardly any, dark brown, I may give them a couple more hours to really aggressively hydrate, and if they're not still voiding or have flank pain or something, I may say, we need to get some labs and get some more fluids and use some vitamins, and we can bring you back to this level of care. Managing risk for return to use, sometimes there is very impulsive stimulant use. Some stimulants are very what patients will call moreish, meaning they want more. The euphoria is very short-lived, rapid onset, and the euphoria, the degree of euphoria, there's also a degree of dysphoria with the drop, and that dysphoria can be for patients as a compulsive reason to reuse, so they don't like feeling that drop in euphoria. And that repetitive recurrent use can lead to particular toxicity as drug to metabolize buildup or by route of administration, or prolonged use and prolonged effects from not sleeping, psychosis, a lot of stuff, so trying to interrupt that in particular binge pattern use is really important. And then you need to have the appropriate clinical testing if someone's confused and altered and you're not able to check glucose or get basic labs, an individual needs to be seen in the ED or even depending on timing as they send out, so all things to consider. Management of acute complications, so we have first steps in managing complications. Identify the cause, if it's other than stimulant intoxication. Again, you need to determine is the patient at the appropriate level of care. Can I rule out other things that are really important if it's not obvious, an altered, agitated patient, can't get blood glucose, they're febrile, can't rule out infection, you really need to get to a setting that can do that, the ED in that setting. Again, use verbal and nonverbal de-escalation strategies to calm agitated patients, but when you don't have those who are agitated or delirious or psychotic and aren't supportive or cooperating with care, they need to be at a higher level of care. Treat stimulant use agitation or confusion with medication if they're not responsive to de-escalation and sometimes you want to still add medications, but your first step is talking to the patient and reassuring. Benzodiazepines, your first line treatment. This is the most common inhibitory drug that you're going to be using. There are other agents as well. Your onset dose drug is going to vary dramatically in how fast they work and the dose by route of administration. Sometimes you need to rely on a particular drug or even non-benzodiazepines because there's drug shortages. In the ED and the hospital setting in the past few years, I've had limited parenteral diazepam, no parenteral, no IV lorazepam, and only a small amount of IV midazolam. So we had oral benzodiazepines, which are appropriate for many patients, but if you needed to give a patient a sedative quickly, we were relying on phenobarbital in that case, which worked well, but it's a much longer acting medication. And you need to understand how to dose and the nuances about duration of effect. And the escalation strategy should not delay the use of medications to patients who are agitated, delirious, or psychotic and imminent for risk for severe complications. Like you see signs that they're really agitated, they're sweating profusely, maybe they have really severe trauma. You need to calm that. That fire needs to be put out now or the house is going down. That's, we need medications. As you're doing an ongoing other assessment, but that's to get this fire put out now. Hyperadrenergic state benzos, our first line, some other agents as well. Antipsychotics often given with benzos. I always use antipsychotics when we have toxic psychosis, paranoia, anxiety, agitation, not improving with standard treatment, prolonged insomnia, several day methamphetamine binges. You can also use them concomitantly with GABAergic agent to the benzodiazepines when you have acute severe agitation. There's studies and debates over which should be first line agents. My preference is the GABAergic agents and benzodiazepines usually, but for the psychosis, olanzapine, quetiapine, for acute severe agitation with psychotic features, intravenous, haloperidol is a variety of different options. Other agents, depending on specific symptoms, some patholytic can be useful, clonidine that dampens down the outflow of norepinephrine, like I use it for alcohol withdrawal. I may give it to complement stimulant intoxication to kind of reduce that outflow of norepinephrine in particular early in the intoxication. Dexmedetomidine, if you're in the ICU, we're not gonna cover all of the drugs that were used. Stimulant-induced psychotic symptoms, treatments anti-psychotic, the urgency formulation and duration based on the etiology and symptomatology. There's a couple of antipsychotics that you avoid. We don't use all of the antipsychotics. We're not gonna use a long-acting injectable during a bout of acute stimulant intoxication, for example. Clozapine, atypical, more side effects, more risk for a seizure threshold, potentially chlorpromazine as well. So we're probably gonna use some of the newer and less dirty antipsychotics in terms of mechanism. If escalating psychosis or agitation, again, conduct a medical evaluation and identify life-threatening signs and symptoms. Did you miss anything? The mental exam status, not just focused on patient orientation, but on their and other individual safety, assessing for hallucinations, and are they able to follow commands, cooperate? Do they understand risks? Are they oriented? Management by symptom, agitation, psychotic behavior, overall hyperhidroic state, hyperthermia, rhabdomyolysis, hypertensive urgency, chest pain. A lot of these are the same initial management that's put out the fire. The stimulant is the cause. You wanna dampen down that fire. So benzodiazepines may be your first-line treatment. The rhabdomyolysis will stop the muscle hyperactivity with the sedative in general, but you also need to hydrate the patient. Some individuals, if they've been on a binge, they haven't been eating well, they may have nutritional deficiencies, so giving them some thiamine, some fluids, some dextrose. Cooling, first line with cooling is to calm the muscular activity, but there's other mechanisms, a fan with ice water, chest pain, cocaine chest pain associated with acute use and hypertension. We have more new discussion in the guidelines, but first-line treatment is gonna be benzodiazepine to calm that acute excitatory state and go from the hypertensive urgency, usually related to basic constrictions. So typically going to use an alpha blocker if they have hypertensive urgency, along with sedatives, GABA-urgent agents. Other management fluids, nutritional support. I already talked about empiric nutritional support, really thiamine, dextrose, vitamins, fluids. Many settings, screen for sexually transmitted infections, screening for stimulant use disorder. Not all stimulant use means that an individual has stimulant use disorder, need to go to treatment. Screen for comorbidities, comorbid substance use, and really important, particular in the era of fentanyl, primary, secondary, tertiary prevention opportunities and resources. Understand your resources available at each level of care and in the community. It's really important. If you're an ED provider, understanding what resources a day clinic may have, an intensive outpatient clinic may have. Sending somebody with mild acute intoxication to an outpatient treatment center, thinking that they're going to have someone medically evaluated with them within a very short period of time. It could happen at some of the settings, but it may not happen for several days at other settings. So really needing to understand what's available in the community. Harm reduction should be considered at all levels of care. Overdose prevention, fentanyl test strips, really important in the era of adulterated drugs, just educating individuals on risks associated with particular use and route of use in overdose prevention, discussion, naloxone availability, even if individuals aren't opioid users, letting people know how common fentanyl adulteration and concomitant use is in today's age. The specific stimulants and pearls, I mentioned levamisone, cocaine. These are some pictures of the vasculitis in an individual that was having a reaction to the levamisone and using cocaine. Get the small vessel vasculitis, also have dropped in neutrophil levels and neutropedic fever. If cardiovascular toxicity and the debate on how to treat cocaine chest pain, beta blocker, can make it worse, can not be in effect. It's a back and forth debate that is very nuanced. We have more discussion of that in the overall guidelines. Cocaine does have local anesthetic effects that's used for numbing, has a vasoconstriction that stops bleeding, that local anesthetic effect in large overdoses of cocaine can affect the heart, it blocks sodium channels, so PRS widening, giving sodium bicarb really important in that setting. Methamphetamines associated with impulsive behavior, traumatic injury, STI prevention, treatment screening, assault, domestic violence can be very high with methamphetamine use. MDMA, you hear about hyperthermia and hyponatremia. Hyperthermia can happen due to the central effects, circumcinergic effects, as well as prolonged muscular activity in areas that are often really don't have great cooling. So at prolonged dance sessions, raves, hyponatremia can be multifactorial. Often individuals are told to drink a lot of water, so they're really compulsively drinking free water and they can drive their sodium down. Sometimes there's SIADH that occurs with the circumcinergic drugs like MDMA. And then MDMA pills can have all sorts of stuff in them. I mean, these are often counter, well, they're not 100% MDMA, but have other stuff from things completely inactive to caffeine, to methamphetamine as a common adulterant, to cathinones, to papirazines, to all sorts of things and variety of different types of MDMA pills. People often talk about like the Green Hulk. It may be a greenish pill that has a Hulk imprint or Gucci imprinted on the label. It's kind of like the imprints on the heroin bags and the slogans and brands. So people can get fairly creative. And counterfeit pills are really the name of the game from prescription meds to illicit pills. And in the bottom, I've got counterfeits. Alprazolam on the bottom right, and then the two middle, those are counterfeit oxycodone. But in one study in Mexico recently, many of the stimulants that were obtained had methamphetamines. So whereas when we think of counterfeit pills, we're thinking of oxycodone, prestoxies, or Xanax. We see more and more other drugs, the stimulants now in the U.S. we're seeing more methamphetamine in Adderall amphetamine pills and methylphenidate to a lesser extent, but to some extent as well. So buyer beware. Stimulant withdrawal or discontinuation is really a state of exhaustion due to neurotransmitter depletion. This is associated with often severe depression. What goes up must come down. Fatigue, dopamine depletion is a state of exhaustion, anhedonia, depression. Other stimulants may lead to serotonin deficiency and you can have that serotonin discontinuation which has some unique features, some neurologic features like people have electrical, brain zaps. The management of this is really rest, put out the fire, make sure the fire is put out so there's not any ongoing intoxication. Nutrition, hydration, sleep, supportive care, helping the patient get to sleep appropriately. Setting that central fire down, you can see that maybe the patient peripherally, they're not agitated, their heart rates come down, they're not sweating, maybe they have a little bit of second motor agitation. They feel exhausted, but they just can't get some sleep. So that's where maybe some olanzapine or quetiapine at night or a dose of diazepam, something can really help if you're at the right level of care, it can help that individual get some sleep. That sleep can be really critical. Look for other comorbidities, infection, wound care, dental. Well, finding dental support can be very hard, but many of our patients really have severe dental problems, caries, and if you have access, at least trying to advocate and set up some sort of method for follow-up. Initiate substance use disorder and mental health treatment as early as possible. Counseling, screening initially, then counseling, whatever you can by resource. There's a lot that can be done in the ED and the hospital, in particular, for patients admitted. There's a lot of resources that tie people into remotely. Educating about overdose prevention, don't use alone, fentanyl test scripts, giving information about how to access harm reduction programs, all sorts of stuff that's available. Drug testing, and I already talked a little bit about drug testing, there's limitations. Toxicology testing can help inform clinical thinking regarding the differential diagnosis, but remember, positive toxicology in urine does not equal intoxication. Think about THC and how long THC can be sitting in the fat cells or even fentanyl in the fat cells and can release over time, so that can positively be detected for weeks in individuals. We can get false positive amphetamine and methamphetamine with bupropion, with pseudoephedrine. So again, problems with drug testing by type of drug testing, as well as applying that to the context, is really important. It does not equal intoxication. Blood levels can correlate with intoxication, but that is not usually something that you're gonna have available right away, and then you need to consider tolerance in that individual as well. You can identify a substance as something where there may be a concern for drug-drug interactions when you're considering pharmacotherapy to manage signs or symptoms of intoxication or withdrawal, but acutely, that's gonna usually be less of an issue, and maybe if I'm thinking serotonin toxicity, I might consider certain antipsychotics out of the picture, but really, otherwise, it's probably gonna have more long-term mental health implications in treatment of underlying comorbidities. Presumptive testing is negative. Doesn't mean that not using a stimulant. I have many consult requests or follow-up, and I say, why didn't you call for toxicology consult in this patient? And they said, oh, their drug testing was negative. We ruled out intoxication. Just didn't understand that they were looking at a six-analyte test that didn't test for everything, so really didn't understand about quite a few different things about toxicology and drug testing, so let's get to our case presentation. Our case presentation involves a 37-year-old named Mr. N. Mr. N has a history of severe opioid use disorder and stimulant use disorder, who smoked fentanyl and methamphetamine and has proved to be admitted to an inpatient detoxification facility in ASAM level of care 3.7. He reports his last use of methamphetamine about an hour prior to presentation, and the fentanyl the same. He's mildly tachycardic. His heart rate is 110. His blood pressure is 164 over 96. His respiratory rate is 24 breaths per minute. His temperature is 99.4. He has mild sweating, dilated pupils, a little bit of psychomotor agitation and anxiety, but he's able to complete the intake process and interacting appropriately with staff. Prior to admission to the unit, staff prepare to search him that he is outside smoking the last cigarette. Shortly after returning from outside, he is searched, brought to the unit, and is noted to be more anxious and pacey. He also gets in a brief argument with another patient in the waiting room, and right when he returned from outside prior to staff grabbing him. He arrives to the unit and is immediately approached as a nursing med window, cuts ahead of another patient and loudly demands sleep medications and in a very aggressive manner, leaning into the window and start leading the nurse. The other patient gets upset. There's a provider on the unit who witnesses Mr. Adams' disruptive interactions. So which of the following is the appropriate first step in this situation? And now we have our poll questions. A, immediately order five milligrams oral olanzapine to help calm the patient who appears to have acute stimulant intoxication. B, call an ambulance to transfer the individual to the ED for a more aggressive treatment, options for his acute intoxication withdrawal. C, start with verbal and nonverbal de-escalation strategies to calm the patient, attempt to identify causal factors for his agitation, perform a comprehensive assessment if he is cooperative and not in acute distress. Or D, administer 10 milligram oral dizepam orally, and then check vitals in an hour. And we have, I think, enough answers. We still have a little bit of time, but the correct answer is to start with verbal and nonverbal de-escalation strategies and calm the patient. And this individual seems to have been escalating since outside, so I'd be kind of concerned, but you give him oral olanzapine, there's gonna be a delay to effect that may be an appropriate treatment after we do an assessment, trying de-escalate and get him away from the window, the other patients. Same thing with the oral dizepam, that may be very reasonable. We wanna keep this individual in an area where we can, first of all, find out, are they at a point where they're still able to be cooperative and interact appropriately? Are they evolving? Did he ingest something right before coming in that's evolving? All right, so the physician redirects the patient using calm demeanor, but Mr. Anderson is sweating profusely and he's having a hard time holding still at this point. He's not just having a second motor agitation, he's twitching, he's tremulous. And he tells the physician, he says, I screwed up, I took the rest of my meth. When I went outside to smoke, I did a line and then I swallowed a gram. He's visibly tachypneic at this point. His heart rate now is via quick check, somewhere in the 140s to 150s, just checking, trying to check his pulse and he's just dripping with it. So the physician asks for an ambulance, called STAT, which of the following is not appropriate given this evolving situation? Again, which is not appropriate. A, if the patient is able to take a dose of diazepam, oral, IV, or IM not available at this level of care, they should receive it as soon as possible unless it delays an assessment by EMS, first responders, or transport. B, obtain a set of vitals, administer 10 milligrams of diazepam, tell the patient to wait in his room, check vitals in an hour to determine the need for higher level of care. D, as long as it's safe to do so, the patient should be brought to a quiet area to wait for the ambulance, ideally out of the regular milieu of the unit while the other activities are performed and the ambulance is en route. Or D, a provider should continue to calm and deescalate the patient while they wait for the ambulance as long as it is safe to do so. And we still have answers coming in, so we'll give it a few more times. Again, this is which is not appropriate given this evolving situation. All right, let's end the poll. I think we're out here. So, the correct answer is B. We don't want to have the patient wait in the room, check vitals in an hour. This gentleman has gotten sicker in the time it's taken to bring him upstairs, get an argument at the med window. He's got to have a core temperature check. He's going to have vital signs monitored via telemetry, not like checked hourly. So, giving this gentleman some diazepam while you're waiting for the ambulance, absolutely, because that would be important. It's important to relay to medics too, and I would probably give him 20, not knowing too much about him, but knowing that he's going to be monitored by an ambulance, and then try and get a core temperature too, if we could safely do that, and that's not going to delay care, and get him out of where all of the other patients are. It could escalate other patients, could trigger other patients. So, we want to try and get him down. We're going to level it as two floors. We want to get him maybe down to the first floor, get some medication in him if it's safe to do so, and get him to the higher level care quickly. All right. So, EMS arrives, gets him in an ambulance. He'd been given 20 of oral diazepam about five minutes prior to their arrival. His heart rate shows 150. His blood pressure is 180 over 110. Temporal temperature is 101. He's decafenic at 32. The medics establish two IVs, start fluids running along with dextrose to give him a dose of midazolam IV, and he's transported to a nearby emergency department with a level one trauma center and a toxicology service, and the ED is brought to the critical care bay and placed on telemetry. His heart rate's on 160 at this point, and he appears to be in sinus tachycardia. He briefly was calmed after the IV midazolam, but is now having trouble sitting in the bed. He is frantic and starting to pull at his IV. Other cords and dress. The ED physician obtained stat labs. There's a rapid physical exam noticing that he's anxious, agitated, paranoid, and hallucinating. His heart rate's in the 160s. He's got markedly dilated pupils. He's got hot, flush, diaphoretic skin. Tremor and tone are increased. He's got left hand swelling and abrasion over the fourth and fifth knuckles, and he winces even with light touch. That wasn't noted before. All the knuckles of that hand are mildly bruised, and swelling is obvious compared to the right hand, and additionally, some areas of excoriations on his forearms from picking and then along his jawline and his left nose. In addition to the labs, EKG, fluids, benzodiazepines, and they use escalating doses of lorazepam IV given right away, and then for symptoms, very moderate to severe agitation. He has an x-ray of his left hand order. There's a fracture of the fifth MCP, metacarpophalangeal joint, which of the following is not true in this situation? A, traumatic injury is less common with methamphetamine use than with other substances. B, common laboratory findings in this patient would be an elevated white count and an elevated CK. C, common laboratory findings in this patient would be an elevated white count and elevated CK. Somehow that would be redundant. That should say would not. So C should say would not include an elevated white count and an elevated CK. That's my mistake. And D, an antipsychotic use concomitantly with benzodiazepines may help with paranoia and agitation. So the two of the same answers, C should say would not. And so your answer would be would common laboratory findings in this patient would not be an elevated white count and elevated CK. So this question was just the answer is misworded. Methamphetamine is associated with a lot of trauma impulsive behavior. This is an excitatory state. So you're going to often have an leukocytosis, not just not from infection. You want to evaluate for infection and other causes of leukocytosis, but just being this excited and excited. Being this excited and agitated, intoxicated, you could have an elevated white count. And that elevated CK is a marker of muscle turnover. I would absolutely expect that. And you can give an antipsychotic with the benzodiazepines in this patient who is paranoid and seems to be hallucinating and agitated. In fact, I would add that adjunctively to the benzodiazepines that they're getting in fiber managing this patient directly. Fully catheters placed, core temperature monitoring or comes back almost 40 degrees. They're getting 4.4, a small amount of dark urine comes back with fully placement of labs show a white count of 17.4. So elevated sodium 143, potassium 5.6, chloride 105, bicarbonate 15. So low, he's got an antidepressant B121 and creatinine 1.3, glucose 165, CK 1150, ASD 324, ALT 111. With escalating doses of lorazepam, it begins to calm down and is ultimately able to sleep. Despite having persistent tachycardia and hypertension, his temperature normalizes to 37.8, so closer to a fever, but improved. A 10 milligram lorazepam had been given IV over the first hour before the escalating Q2 overdoses. He also received five milligrams of IV haloperidol at some point adjunct to the lorazepam, so they followed my recommendation. Fluids are running at two times the maintenance rate, along with some thiamine and some dextrose, and other nutrition labs are repeated, as well as a lactate and blood gas, and he is admitted to the ICU overnight for continued monitoring and treatment. Depending on what's available in the hospital, he might be appropriate for just telemetry as well at this point, but you'd have to make that decision earlier and get this guy aggressively treated, make sure that fire is put out. All right, so at this point, I think we have time for Q&A, and I'll turn it over to ASAM for directions for asking questions, but I think it's just simply through the Q&A, and I can stay on for some additional time here. Yeah, Dr. Wiegand, I know we're right at the top of the hour, so if folks, if you're available to stay on for a few minutes, we can stay on, and then we also, I was talking with Dawn, we thought maybe we might see if you could answer the Q&A questions, and we could send the participants the answers directly after the webinar, just to make sure the questions are answered. I can do both. I can stay on and answer, and then I can also respond to make them available so everyone has, but if you're able to leave, if you're unable to stay on, so we'll do both. Okay, perfect. And then you have how to claim CE as well, did you want to? Yes, so before everyone hops off, yes, claiming CE, so we will be sending out an email to you all. It might not be this afternoon. It might be first thing in the morning, but you will receive directions with logging into your ACM account and claiming your CE, and then also did want to remind you all of the next upcoming webinar with Dr. Brian Hurley, so that is on March the 6th, so please register for that webinar. We would love to have you attend that as well, but again, your email should be in your box in the morning, so thank you all for being here, and Dr. Wiegand, if you can stay on for a few minutes and answer questions, that is fantastic. Absolutely. I wanted to give a plug also. I have a monthly case conference that's usually the first Friday that's jointly sponsored by the American College of MedTOX and the American Society of Addiction Medicine related to addiction toxicology, and our next one is March 1st, involves chem sex, so usually some stimulants involved there. That's one. You can check the ASAM website or ACMT as well for registering for that as well, or email me if there's any questions. Email information should be available, so let me look at the Q&A. I'm interested in knowing more about the transdermal route, common questions that my patients raise. There's less transdermal stimulants than I'm aware are available. There are some that I believe are available for Parkinson's disease, but that's not going to be something typically used recreationally. The rectal, probably more often, and then oral crushing, swallowing. Transdermal issues can come up if people are doing things like manufacturing methamphetamine, getting some chemical spills on, some corrosive agents. That may be an issue, so sometimes collateral information, fires, burns, things like that. We have less of that now, so then more meth coming from just large cartels, distributing higher quality, but still an issue in some areas. Then we have a question, is intranasal route quickest and most potent for all drugs, or is that unique to cocaine? The intra, inhaled, volatilized, is the most rapid way to get the drug delivered to the brain, the most intense and rapid rise of dopamine. Intranasal is actually going to be much slower than smoking or intravenously, so those would be the two quickest routes. Intranasal, close to probably sub-Q or IM, but there's a delay. If you look at the graph I have of concentration over time, it'll show that intranasal is going to be slower than smoked or volatilized and intravenous. Tim, I have a question. I've put on 10 milligrams of methadone twice a day for pains as opposed to resection, parts of the jaw, and also on Trexone, 50 milligram orally daily, which is used to stop drinking alcohol. Can this have any effect? He said it did. I think that's separate. I'll answer that offline. Can the person get rhabdomyolysis from being toxic? When I talk about intoxication, the degree of intoxication is like the degree of fire, and the degree of intoxication, if it involves muscle hyperactivity, movement, or the temperature is up, that causes muscle turnover. We have rhabdomyolysis or muscle breakdown anytime we go running or to the gym. The degree of rhabdomyolysis depends on the degree of muscle turnover, the temperature, how long we had exercised, how much we run. A marathon runner that is running up and down hills and it's really hot out is going to have much more rhabdomyolysis than somebody that's running one mile in a cool environment. The same thing with stimulant effects. Somebody could have mild stimulant effects, so their heart rate's up, their pupils are a little dilated, they have a little psychomotor agitation, and their CK may not be elevated at all or very subtly elevated. That doesn't require clinical significance. Can you get false positive methamphetamine drug screen when just scorpion bite? No, no. It's not a false positive. The clinical effects from the scorpion venomation look like methamphetamine intoxication in a toddler, so they get real excited. Sometimes when in the Southwest, colleagues that if the family has known that the toddler has gotten into methamphetamine accidentally and they don't want to disclose it, they may get in a lot of trouble. Get CPS involved, and so they may use that as an excuse that why the child is acting associative or they may not understand that the child got into the methamphetamine. It's not that that causes a false positive methamphetamine on the test. In fact, the test would rule out or rule in methamphetamine exposure in that setting. There was one example of where testing might be useful in one particular population, not that even then, not that it caused the intoxication. You'd also have to be careful. It could be that the exposure occurred a couple of days before, probably less common if they look like they're on methamphetamine, in fact, but it's not that it caused a false positive drug test. Bupropion is a cathinone derivative. It's a beta keto end tertiary butyl orthochloral beta keto sun ethylamine. Yes, if I had a structure or if I had a chalkboard, I would draw bupropion and a toxicologist. Yes, it is a cathinone. It is the only cathinone phenethylamine that we use pharmaceutically. Does the hyperadrenergic state result from direct effects of the stimulant or do these drugs cause release of endogenous catecholamines or both or both? Both to some extent. There's differences. Cocaine blocks reuptake, for example. Methamphetamine blocks reuptake as well as a releaser. There are different effects. Some of the stimulants also have serotonergic effects, release, reuptake. Not all stimulants have the same mechanism when it comes to the effects on the catecholamines. The stimulants that are used recreationally are involved in the reward circuitry and are affecting dopamine levels at some point, causing reinforcement. Their overall mechanisms may be much more complicated. In fact, many of the effects could also be even non-stimulant related. Some stimulants at high doses can block the potassium channel and have cardiac effects, bupropion one, or block sodium channels. Bupropion, again, a really severe bupropion overdose or somebody binging on bupropion could have some cardiac effects that are kind of difficult to treat. There are some other effects as well. Do many patients use the rectal route to administer these drugs? I think that depends on subpopulation and also by drug. If a drug is largely metabolized via first pass metabolism, broken down by the gut, liver, they're trying to bypass that. Absorption, there's even slang around this. People call it booty bumping. Interesting culture around sometimes it's being used. The rectomycosis drugs can get absorbed across it fairly well. It's just considered another route of administration. Chemsex sometimes used this route of administration. Cocaine to numb. In that context, you also have to consider abrasion due to particulate matter, increased risk for STI, depending on other behaviors, but not all drugs are used rectally and not all drugs are going to have very differences of absorption. Certainly intravenous or inhaled or volatilized, if a drug is amenable to those routes of administration would get the drug much quicker, efficiently into the brain. I think also population, some individuals are going to just not be amenable to that. Others would consider, maybe I'll try that. How significant is stim-induced cardiomyopathy associated with morbidity, mortality-related arrhythmia, heart failure, et cetera? That's a great question. It comes up in review of cases, I'm reviewing post-mortem drug levels and death, trying to determine is this a stimulant-related death or is this a, is it but for the fentanyl or something? Much less than when you have opioid use concomitantly, it's typically going to be the opioid that causes the stimulant effects. But we know over time, cocaine, methamphetamine, heavy persistent use can cause cardiac effects. It can cause contraction band necrosis of the heart, can cause cardiomyopathies, use of cocaine with ethanol, cocaethylene can accelerate atherosclerosis, have prolonged effects. So not great drugs for the heart chronically over time, but acutely usually when somebody dies from a stimulant, it's not usually from an arrhythmia, possibly, usually patients have underlying conditions, it's possible, but it's less likely. It's more due to the hyperadrenergic state, the hyperthermia, hyperkalemia, acidosis, which ultimately that would cause an arrhythmia and death, but that's not directly related to the stimulant effect on the heart per se. So a little bit more complicated answer, some variation depending on stimulant. There are some particularly toxic stimulants in terms of the heart with different effects. Some stimulants have much more alpha effects, so vasoconstriction compared to others. The reinforcement repetitive recurrent use will also have an effect on the heart. So really a lot of variability depending on the stimulant pattern of use. A great question. I have noticed that most of my clients have low CO2 levels. How would this relate? I'd have to see the context. And I'm assuming that if you're in the ED and you're looking at not just low CO2, is this CO2 or is this bicarb? If it's low CO2, that means they're blowing off CO2 and they're probably trying to compensate a lactic acidosis. And that would be concerning. That's like when I was saying that the more severe patients with stimulant intoxication, severe agitation, that we used to call excited delirium, would be the patients that are hyperthermic, really acidotic, potassium shifts out of their cells. They're really breathing fast because that blows off the CO2, which is an acid, to try and compensate for that metabolic acidosis, which is driven by the stimulant intoxication. So that's the setting. That's what's going on. If it's bicarb, it's an anion gap acidosis. And so low CO2 or HCO3 on your Chem 7 or BMP is another indication that there's an anion gap or an acid there as well, probably lactate. So it could be a concerning marker. Great presentation. Thank you. Oh, you have a question as well. What are your thoughts about amphetamine-assisted treatment for stimulant use? And can you talk about any success with antidepressants or mood stabilizers in early recovery from stimulant use? Great question. We have one of the modules related specifically to treatment later in this course, so I'm going to save that answer because it's a much more complex and nuanced answer about this, but it is covered during this series and in our guidelines, absolutely. Does the use of vitamin C help with dopamine replenishment during meth withdrawal? No, I'm not aware that it does anything to vitamin C. Sometimes you hear about acidifying the urine to enhance amphetamine excretion, I think, which we typically don't do. Just hydrating the patients is typically more important, and there can be some other issues related to urine acidification that can cause some complications. Vitamin C in general, just orally giving someone multivitamins nutrition, I think, is fair, but I'm not aware that it has any effect on dopamine replenishment during withdrawal, but nutrition multivitamin is certainly absolutely important during post-intoxication or withdrawal. Hello, can you please explain the difference between methamphetamine and dextroamphetamine? Many patients with d-methamphetamine blame Vyvanse. I am constantly asked this question as many medical people seem to be confused. Dextroamphetamine is a d-enantiomeramphetamine. D-methamphetamine is the d-enantiomeramphetamine. I would draw this out if I could do this on a chalkboard, but each drug that you have, you have an R and S or a D and L, so the two enantiomers. Think of citalopram and escitalopram. Escitalopram is the S enantiomer of citalopram, which you have citalopram going to be S and the R enantiomer or the D and the L enantiomer. So two different drugs with Vyvanse have less dexamphetamine. The lysine is cut off after absorption. The idea is that it has a slower onset of effect, so to delay the reward, to potentially delay the abuse potential, but is dexamphetamine, not dexmethamphetamine. Historically, there have been some methamphetamine preparations available in clinical use, even over the counter in some nasal sprays, but the most common ones, the Vicks menthol nasal spray that people have used, used to have the L-methamphetamine enantiomer, which didn't cross the blood-brain barrier, just caused peripheral effects. It didn't cause any euphoria. And so to have some patients blaming, oh, I used the nasal, not the Vicks menthol nasal preparation. Most of those, to my understanding, have been removed and we don't see those anymore, but it is absolutely not the Lys-dexamphetamine. What I see now is more counterfeit tablets that people are using that have methamphetamine used, and somebody told them that they're taking, usually it's Adderall, but it could be any of them. It's more commonly, and I'm probably coming up from Mexico, counterfeit drugs are the name of the game, people making billions off of this. And they have often methamphetamine in them, and it's true methamphetamine. And so methamphetamine, when confirmed, it's methamphetamine, not dexamphetamine. Email me if you have other questions on that. Are there any specific vitamin deficiencies that are most common in these patients? Can any of these cause acute cardiac complications? I think I answered the cardiac, so you can get sometimes acute vasoconstriction, hyperthermia can have cardiac effects, acidosis can have cardiac effects. The comorbid use of other drugs often is a concern. I think the most common issue when people are binging on stimulants is the dehydration. Any patient that's coming in and getting some dextrose and thiamine first with dextrose because you want to make sure you treat what could potentially cause the most problems or kill an individual. But a lot of individuals are malnourished depending on the degree of use. Also, you may want to supplement certain vitamins, nutrients if somebody has a lot of wound care needs, zinc, things like that. So malnutrition can be really common in our patients. There's a lot of concomitant alcohol use disorder as well. So thiamine, folate, problems. What are the benzodiazepines of choice for this? More fast acting with long half-life really depends on what's available and how long I think the clinical effects are. How quickly do I need to get this under control? So it really would depend on your level of care. At the 3.7 level of care, we have oral diazepam, which is a pretty quick acting, very bioavailable benzodiazepine that it's going to work pretty rapidly. Certainly not as quick as IV. In the emergency department, if we have somebody that doesn't have an IV, we use imidazolam, but that's a short acting benzodiazepine, but intramuscularly can be very quick acting. Parenteral lorazepam is a very quick acting, so we can be preferred to give lorazepam parenterally. Some of this comes down to also shortages and what's available. So just being familiar with a couple of different options and if there are drug shortages, in particular at your level of care. Sometimes it comes down to cost. I think the VA hospital system still uses a lot of chloridized epoxide. It's much less expensive, only orally long, long acting available in meds. It's a lot of metabolites, maybe not quite as safe as somebody with liver disease, but it's still going to be effective if dosed appropriately. In over-treating with benzodiazepines, you run into delirium and persistent sedation. So you want to have a usually a shorter acting titrate to effect unless you know that this is going to go on for a while and you're in a setting that you can monitor. Yet you also don't want to give a really short acting benzodiazepine like imidazolam as your only benzodiazepine unless, you know, it's by necessity out of route of administration. You know, there's a reason why it's used for procedures. So you can sedate somebody, a lot of amnestic effects, but it wears off quickly, so you can safely send the individual home. Are there any special considerations for medication use in adolescents intoxicated on stimulants? I can think of, in terms of treatment of the intoxication, just really dosing appropriately. And that's really it. You use the same types of medications to put out the fire, really. Maybe some differences in treatment potentially, but that can be, we're going to address that later on. Are anti-psychotics used for stimulant psychosis? Prestidex, I covered that during this. Yes, anti-psychotics are used for stimulant psychosis. It can also be used concomitantly for severe agitation to, you know, get somebody home. You need to get them calm, relaxed. I mean, there's a theoretic concern about seizure threshold. And many anti-psychotics have a lot of other effects compared to benzodiazepines. So QT prolongation, lower seizure threshold, maybe alpha blockade. Some of them can be serotonergic. So a little bit messier, but clinically in the studies that have been done, looking at some specific anti-psychotics that often is less of a concern, but with specific anti-psychotics, stroparadol, haloperidol, pre-hospital setting. For toxic psychosis, I will often give a benzodiazepine along with a dose of an anti-psychotic. A patient coming in with maybe mild stimulant intoxication that's kind of dampening down to the 3.7 level of carol has five milligram doses of diazepam available based on symptoms. And then olanzapine, five milligrams available, maybe once when they come in or to try and get to sleep. And then at night, if there's difficulty sleeping for a couple of nights or some paranoia, something like that, quetiapine is another reasonable agent to use in that setting. You just don't leave them on it as a sleep med persistently because of all of the metabolic and toxic side effects that you can see when something like that is used for prolonged period over time and not for just psychosis. What would be a typical dosing strategy for use of phenobarbital to manage acute stimulant intoxication? When we had the benzodiazepine shortages in Rochester and I think, well, we've had several issues with IV benzodiazepine. So first you think, okay, can the individual take an oral benzodiazepine? I usually use the 130 milligram, uh, uh, parenterally. If I have the shortage of IV benzodiazepines and then titrate to effect, it really depends on the degree you can give, um, you know, barbital pretty quickly and titrating up the doses. Um, so mild and moderate, um, I may give one 30. If I don't see a response, I'm going to pretty quickly escalate the dose, um, up to 260 and then maybe give 260 milligrams every 30 minutes. If you're giving, you know, barbital in that context and they're still having a lot of signs, you know, symptoms or your temperature is still up and you consider other agents like intramuscular ketamine, it really works quickly and it's a great agent for, um, rapidly controlling, uh, agitation or severe agitation. So I would, um, go to that if, uh, some 130 milligram doses of phenobarbital not working. And I'd be happy to share it with phenobarbital protocol as a benzodiazepine substitution. When the IV parenteral benzodiazepines weren't available, I would say anyone if they email me, um, but that's not in lieu of benzo only it's when we had shortages. So it really depends on the context. There's a lot of nuances to specific, um, use of the drugs depending on the degree of intoxication, your level of care, what's available and, uh, severity of intoxication. Uh, let's see. What is the longest time you have seen psychosis from stimulants? Chem sex weekend without agitation, persist. Well, you usually with psychosis, well, you can have a hypoactive delirium, you can have a hyperactive delirium. It depends on other drugs present. Um, I've seen individuals with some of the cathedrals, uh, struggle with psychosis for days and days. And then even when, um, they've been put to sleep, they wake up with a persistent psychosis. I think sometimes then it gets, okay, is there an underlying risk? Did we like with some of the cannabinoids, um, push somebody into psychosis that's maybe prone to that. It doesn't come up as often. Um, I think most commonly we're going to probably where all of us practice, we're going to see it with methamphetamine and it's going to be with prolonged binges and really getting that individual to sleep, um, hydrate the nutrition. Um, they may wake up and still not be quite back to normal, but again, that's where ongoing nutrition, ongoing sleep restoration, restore, um, you know, the overall health of the individual, calm environment. A lot of, uh, concomitant, um, mood disorders, um, mental health, um, support needs to trying to determine underlying comorbidities as well. Really important. Um, individuals, a lot of individuals that use stimulants also have, um, really severe mood disorders, uh, schizophrenia, bipolar affective disorder, maybe that's underlying and been untreated or, um, compliance issues as well. So you need to consider each patient separately. Uh, can you view doses for the medications recommended for acute intoxication? We have a table in the guidelines that I'd refer you to that, um, we have some examples and, um, for different drugs and otherwise if there are particular questions, happy to go over that. I could send email follow-up. I've been seeing a lot more acute psychosis. What is your go-to antipsychotic? Um, it depends on the setting. I already mentioned in, uh, in, um, the detox level 3.7 level care, usually we'll use five milligrams of olanzapine, um, in the hospital setting and that's, uh, had been on formulary. So it's other providers use it and I'm comfortable with it. In the hospital, in the ICU, if it's severe quetiapine, I like it at night. It doesn't complements the other drugs, nicely helps patients with more sleep wake. I think there's olanzapine would work probably as well. It depends also on route of administration. If you have to give IM olanzapine, um, if we want a really quick acting drug that no over time has been done safely, I like to repair it all. Um, you know, especially when there's other drugs on board too. Uh, you know, there was a black box warning historically with droperidol. That's, um, less, much less of a concern with that. A lot of clinical experience using droperidol acutely or otherwise haloperidol. Those would be kind of the probably four different options that I'd be looking at depending on the level care context and, um, the severity. It also depends on what other symptoms they don't reach just for an antipsychotic, just for the stimulant intoxication. It's just kind of a stepwise approach. In standalone, uh, psychiatric hospitals, no IV access, what would be a reasonable threshold of CK levels to send an ER for IV fluids? It really depends on patient and are they able to hydrate? Are they voiding? So I ask a patient, um, are you able to keep fluids down? And then how often are you paying? And, um, let's get you hydrated quickly. Also, you know, somebody that was older, concomitant heart failure, you know, maybe takes a diuretic at baseline, it's been off their meds. That would worry me much to a much greater extent. Maybe it occurred to me myopathy compared to a young, healthy individuals that, um, was suicidal, um, and had been on a stimulant binge and, um, was able to take fluids and was telling me that, yes, they're peeing and that's, yeah, it's a little darker, but it's getting better. Or, you know, we can even have them, you know, pee in a cup and check the, the, is it like looking Coca-Cola covered or like it sat on a shelf for a week or is it looking like normal urine? And, and, uh, you know, so those are the things I'm going to be looking at. Um, and I think you can get pretty good history at least in, in that context. Would you also, I'd want to know a little more about the history too. I mean, were they, you know, has this person been found, you know, outside wandering, medics tried to bring to the ER, they refused, went home. Did they get the appropriate evaluation before getting to the psychiatric hospital? And what, you know, what, what is their mental state too? So I might want to know how reliable are they with that history? Uh, next one, would you recommend or consider chlorpromazine or clozapine with a patient with stimulant use disorder? Will it add risk for seizures just in case increased, just in case increase in stimulant use? I usually don't use those two. That's, there's a slide that, that those two in particular, usually are referred to in the reviews as having more, the, the higher risk for seizures. And, um, chlorpromazine is very dirty drug. When you talk about pharmacology, it's very anti-muscarinic. It is very sedating. There are a lot of alpha blockade, uh, QT prolongation, um, a lot of effects with a clozapine. Um, I don't prescribe clozapine or use it in any, usually you will see it in the context of movement disorders or, uh, side effects. Um, uh, a couple of adulterated, um, heroin samples with clozapine where individuals ended up very anti-muscarinic. So as I mentioned, I think the antipsychotics that I talked about earlier are much more utility, um, in not necessarily one better than the other, depending on, um, dose and acuity and level of care. Are patients stating that they're willing to use fentanyl test strips? It does require the user to waste some of their stash. I'm just curious if community members are actually using them. Uh, it's a good question. I recommend it. I know patients using them. I think it depends on what drug it is. Um, and they also need to use them correctly. So not just, um, instructing individuals, um, using, um, the fentanyl, um, test strips, but using them correctly. Um, you know, most cocaine users, when I talk to them about fentanyl, they would much rather, or in particular, give them some examples, um, obviously without using names of patients to identify information of, you know, some accidental fentanyl exposures, um, seem very willing to take the fentanyl test strips that we have and follow through. And I know a lot of individuals using it, finding fentanyl, um, you know, with opioid users, um, I think, you know, there, you know, I've heard individuals, you know, say they're going to use it in many areas. I don't think there's no real heroin. Almost all heroin is, uh, fentanyl or fentanyl analog, mostly fentanyl. And there it's really important if they say, well, I'm still going to use it, use it to remind them not to use alone or the Oasis, the Office of Alcohol and Addiction Services has resources and a number you can call that, you know, you, you, um, will be technically using with someone on the other line. And if they don't, um, get a signal from you, they can call EMS. It's a great opportunity to remind individuals of the Good Samaritan Law, if it exists in your state, um, and, you know, the other harm reduction efforts. So I think very important, um, in this era of fentanyl, almost a bell trading. And Dr. Wiegand, I don't mean to, I don't mean to cut you off, but we are at 432. We actually need to hop off the zoom platform. Um, so if it's okay with you, I can send on the Q and A report and you could potentially review it and see if there are individual questions that we could answer. Sure. No, there's some great questions. I'm answering them. I was wondering when I was going to get cut off because I can go on, but yeah, that works fine with me. Okay. Thank you, Dr. Wiegand. I will send that to Dawn and then thank you to everyone who stayed on. You should have already received the email about the CE credit. So thank you so much. All right. Thank you all. And, uh, yeah, have a good afternoon. Hope this was useful. Thank you, Dr. Wiegand. Bye-bye.

stimulant intoxication

withdrawal management

acute complications

patient assessment

toxicology testing

agitation management

medication use

harm reduction

overdose prevention

withdrawal symptoms

supportive care

emergency department counseling

adolescent medication use