 You'll see in a minute that incapacitating is such an ambiguous term that it would be best not to have to use it at all, but we have to use it. In this particular lecture, we're going to talk about some other agents that are incapacitating, not by virtue of local irritant effects, but by virtue of some other effects. And what I'd like to do is talk a little bit about the definition of incapacitation, because that's a very misused word. We'll go over the history and the distribution of some of these things, and some representative compounds, and then a specific group of compounds, of anti-cholinergic compounds that we'll discuss. Now here are some people, you've seen this picture before, on more than one occasion. Are these people who are effectively blind, even though they're not really blind, if you could open their eyes, they could see, right, with mustard? But they can't open their eyes because it hurts too much. Are these people incapacitated? You bet they are. They're incapacitated by virtue of the fact that because of a medical impairment, something that we could measure, they actually are disabled from performing their particular military mission. Well, incapacitating agents are agents designed to incapacitate people, but not necessarily in that way. Incapacitating agents are designed not really either to kill or to injure somebody seriously. They're designed to produce temporary inability to perform a mission, by disorientation, by other temporary effects, but the end result is inability to perform the mission. Now, what does incapacitating mean? Well, there's a general dictionary definition of incapacitating, isn't it? Incapacitating means something that renders somebody powerless as in an incapacitating disease. We don't have to refer to chemical warfare agents at all to use that term in that way. Now, we can also use incapacitating in the sense of an ICT50. Remember I said, what's an ICT50? It's the dose that causes incapacitation that is a certain effect in a given individual. So if I'm talking about an ICT50 for meiosis for nerve agent, yeah, I can use that. What did I say a better term would be? Effective CT50. Excellent, very good. An ECT50, because meiosis may be incapacitating if you have one MOS. It may not be incapacitating if you have another MOS. If you're a soldier firing a rifle and the person's in fairly close range, it may not be that incapacitating. If you're an aviator, very incapacitating to have meiosis. And then finally, the most specific definition of incapacitating is referring to this particular group of compounds that we're going to talk about. Now, remember, here's the general classification, toxic agents versus incapacitating agents. And the incapacitating agents include a compound called BZ and another compound that probably none of you has ever heard of that we're going to talk about. In fact, that none of us had ever heard of until very, very recently. OK, now, what kind of incapacitation do we want when we talk about incapacitation? Well, we want something that's not going to last a long time. We want something that's temporary. We want it to be significant enough that it will prevent the enemy from fighting us or prevent the criminals from hurting their hostages before we take them over, that kind of thing. And we want it to be non-fatal. Big push for that. And there are various ways that we can do that. We can give somebody terrible diarrhea. And as long as it's short enough on set, yeah, that may be incapacitating. But more the search in the last several decades has been not just for compounds that would induce diarrhea or nausea or hyperthermia or something buzzing in the ears but something that would produce some mental effects. Disorientation. Change in sensorium. Change in behavior. In coordination. Inability to focus on task. Now, how would we use incapacitans? Well, we could use them in the military. Large-scale battlefield use. Is that very practical? Not really. But special forces might use an incapacitant to take out somebody in a room this size, put a little hose through the door and give us something that we wouldn't know about until we're already disoriented and unable to resist. In civilian settings, where would we use an incapacitating agent in a civilian setting? Waco. Ooh, Waco. Now, that's a good example. Now, what were the constraints at Waco? What did we want to do? There were people there who apparently had hostages or at least what the FBI considered to be hostages. What were the goals? What would have been the goals? If somebody had asked you a medical, your medical opinion about what kind of an agent could be put into that compound in order to work, what would you say? What would be the criteria? Oh, yeah, put mustard gas in. I heard that. Now, that's a great agent. That probably would definitely put out of commission, if by that definition, if that's what you mean by incapacitating. But it will also hurt whatever hostages might be there, right? Whatever innocent people might be there. So you don't want any of the toxic agents. So mustards out, nerve agents out, cyanides definitely out, pulmonary agents are out. What about riot control agents? What was wrong with riot control agents? Obviously, riot control agents were used for a certain purpose, and in that they failed. Why didn't they work? Part of the problem was that these were explosive. It may have contributed to the genesis of the fire that destroyed the compound. But part of it also is that, first of all, you can have tolerance to riot control agents. If you're extremely motivated, you can fight through riot control agents. We know that from what happened in Vietnam, in the tunnels. Lots of people just stayed in the tunnels. And you could put as much riot control agent as you wanted. And as long as you didn't reach that extremely high level at which people would die, people actually could continue to fight. They weren't, in fact, as incapacitating as we wanted them to be. But more than that, there's enough time that you can warn other people and put on a mask if you have a mask. There are other things that you can do. We'd like some compound that would be such short onset that nobody would have time to warn anybody else. You'd become disoriented immediately and be unable to do what you're going to do. We'd like the effects to be predictable. In fact, we can develop a list of criteria, say, in military settings. What would be our criteria? Well, we'd want something that has a high potency. We wouldn't need too much of it. So we want something with a high safety ratio, like riot control agents. We want something that's feasible, maybe a fairly short duration. And we want something where the effects are reproducible and predictable. How reproducible and predictable are the effects of riot control agents on the body, physiologically? They're pretty reproducible. Almost everybody, unless you develop tolerance, will develop some irritation, eyes burning, coughing, sneezing, that sort of thing from CS. How many of you were in the gas chamber and didn't have any of those effects? Okay, so the effects are fairly reproducible physiologically, but they're not very reproducible from a behavioral standpoint. What is, what's, what your reaction to CS is may not be your reaction. I mean, everybody wants to run out, but some people might, some people get agitated, some people, you know, the same, that is also true for most of the mentally incapacitated agents. Well, let's look at it from a civilian standpoint. Okay, very short duration of effects, less than an hour. It would be nice also if we had a specific antidote, so that if any of the hostages really got a little bit of an overdose, we'd have something immediately to give to them to make sure that they came out of it all right. And again, reproducible and predictable. So far, that's been a search that's been largely fruitless. People, agents that have been considered are volatile anesthetic agents, you know, what's wrong with that? Okay, it's not predictable. And the other thing is, the safety ratio isn't very, isn't very high. By the time you get somebody that's out, there's respiratory depression that's setting in as well, and there's not a great deal of difference between the dose that puts you out sometimes and the dose that will kill you. Same thing with sous fentanyl, some of the fentanyl congeners, the opioids, anti-psychotic compounds, haloperidol, and not a very, but what's wrong with haloperidol? Withalda. How long does it take to act? I mean, you don't have immediate, so obviously too long for that. People have looked at LSD, what's wrong with LSD? LSD is very disorienting to some individuals. Okay, again, and there are plenty of compounds that you can give to people where your reaction might be to be very dreamy and be absorbed in your own hallucination, your reaction might be to grab your rifle and be more aggressive. And as long as the effects are that non-reproducible, these compounds don't really work very well. Now, the last compound, the last group of compounds, the anticholinergic compounds, probably come closer to this goal than any of the others. And that led to weaponization in the United States of a particular anticholinergic compound that we'll talk about. But these things are not really new. The search for agents that are not necessarily toxic is an old search. We know that at least as far back as 600 P.C. we have people like Solon who threw roots of a particular plant into a river and the people that drank from the river got diarrhea, you know, incapacitating from a physiological standpoint, not necessarily a mental one. More from a mental standpoint or at least a mental status standpoint is the use by the Carthaginians of wine that was laced with a particular drug that made people really sleepy. And it was really good wine. Hannibal, the guy who crossed the Alps on the elephants would, when he was at sea, throw pots full of snakes under the opposing vessels. They didn't need to be venomous snakes. They didn't have to cause death by bites. Just the fact that snakes inspire fear was enough. And that created enough panic that it gave or at least he thought it would give an edge to his troops. And the same story, Belladonna alkaloids. Where do we find Belladonna? Where does Belladonna come from? The plant, what's the plant called? No, that's digitalis. No, that's opium. Deadly nightshade, okay, deadly nightshade. And Belladonna is the source of several anti-cholinergic compounds. What happens when we, you know, there are other anti-cholinergic compounds in Jimsonweed. Anybody ever treated a Jimsonweed? Very good. You're from the West? Yeah, okay, often there's people who do that. And what kind of effects do you get from that? Holocenations, ooh, very interesting. We'll talk about that. And of course, Hashish, the word assassin comes from Hashish because Hashish was fed to these people to give them, to inspire fearlessness in what they were to do. Now here's some Afghans and there was some concern that maybe the Russians in more modern times may have used some kind of an incapacitating agent in Afghanistan. We have no concrete evidence of that but there were certainly plenty of reports. There were also reports that the Soviet Union before its dissolution may have used these things internally. POWs came back saying, well, they used, the Koreans used some sort of weird thing on us to make us so that we wouldn't fight. We're not sure. We don't have any concrete evidence of any of these things. But there are plenty of reports. Military's been interested in psychedelic compounds since they were first reported. LSD, oh, you know, you can imagine what somebody might have thought the military or Secret Service potential kind of, for this kind of compound might be. But again, as we've said, the effects are unpredictable. Never did these things really pan out. However, the United States did go ahead and investigate one of the anticholinergic compounds in enough depth to weaponize it, put it in munitions, store it for a long time. Now, here's Iraq again and here's a munition with chemical agents in it. Until very recently, the chemical agents that we thought that Iraq possessed included GA, GB, VX, mustard, and very possibly cyanide, and nothing else. And that's one of the reasons that we dropped the incapacitating agent's lecture from this course. We used to have it and then we thought, well, you know, it was just BZ. We started to destroy our stocks of BZ in 1988. They're almost all destroyed. And there's not really any use anymore for giving this particular lecture. However, February 9th of this year, just last month from Reuters in London, Britain on Monday released what it said was new information on chemical weapons which were in Iraq's arsenal at the time of the 1991 Gulf War. We have recently received intelligence indicating that Iraq may have possessed large quantities of a chemical warfare incapacitant agent known as Agent 15, Defense Secretary George Robertson said. The Ministry of Defense described Agent 15 as one of a large group of chemicals called glycolates, that's the British spelling, which interfered with a central and peripheral nervous system. All of a sudden, incapacitating agents are back in the news. They may, in fact, be a threat. You may yet encounter them on the battlefield. So what are they? Well, the old way of classifying incapacitating agents was to say, some of them stimulate the central nervous system, some of them depress the central nervous system. Fairly general nondescript and not terribly useful classification. A more recent and better classification is to split these things into four categories. There are the CNS stimulants like amphetamines. Which one would amphetamine as a, I mean amphetamine will make people do weird things, isn't, why wouldn't we use that as an incapacitant? Makes you aggressive. Okay, because in a significant number of people it inspires greater resistance to the enemy and more aggression, okay. But there are a whole list of CNS stimulants that might be used, strychnin is so stimulating that causes convulsions. Well, obviously now we're going into the toxic group of compounds rather than just incapacitating groups. CNS depressants, depressants, barbiturates, opioids. Most of these have problems either in a safety ratio that's unacceptable or in a long onset of action. So they're not very useful. The psychedelics, again, problems with unpredictability. But finally, the delirians. The delirians include drugs like the ones found in Jimson weed that will induce delirium and hallucinations. And they're usually the antico-energics. BZ is one of them. Agent 15, we're not sure exactly what kind of an antico-energic it is. It may be a carbon copy of BZ, it may be BZ. It may be something closely related. So let's look at the whole class together since we're not exactly sure which glycolate may be used. Remember the Reuters report said these are a group of glycolate antico-energics. Well, glycolates are just nothing more than esters of glycolic acid, very simple compound. They all have the two carbons in the center and that particular structure that you see. Many of them also have a benzoyl group off to the side or a phenyl group off to the side. So there's an aromatic ring in there somewhere as well. And there's a wide variety of them. BZ is the one that we chose to weaponize and that we chose to investigate. And we do have field reports about how BZ affects people. BZ itself is the other kind of agent that's a solid. In fact, it's a lot like riot control agents in that. It's a solid, except that the melting point is so high that you will never encounter the melting point in the field. So even if you explode this with a munition, it always comes out as a fine powder. If the powder is fine enough, you may not be aware that you're inhaling the stuff. Now this is a difference from riot control agents. What's the onset with riot control agents? Immediately. You'll find out that that's not the case necessarily with antico-energics. Now what other antico-energics are there? Well, there's atropine. How do we know about atropine? I mean, what else do we use atropine for? Nerve agent, ooh, ooh, remember that. Because all of the antico-energics are essentially will give you the results of too much atropine, just in varying degrees. But there's scopolamine used in anesthesia. Ditropan also used sort of obsolete now. Why does an over-the-counter antihistamine make your mouth dry? Because it has antico-energic properties. And many of the antihistamines have antico-energic effects. Benactazine, deserves mention, because benactazine is an antico-energic that we actually used to use as an nerve agent antidote. There used to be something that we called TAB tab that was a mixture of three compounds, TMB for atropine and benactazine, which is this other antico-energic. But what do they do? They block acetylcholine. They're duds in and of themselves. Atropine doesn't really have, I mean, it has a few minor primary actions, but its major action is to block acetylcholine. And for these agents, we're talking about central effects and peripheral effects. And that'll become important in diagnosis because the patient will present to you with peripheral effects and also some very significant central effects. And if you see the hallucinations and you also see at the same time some peripheral antico-energic effects think, antico-energic think, incapacitating agent. So you remember this. You remember that another version of this was shown you earlier where we have the little green dots which are acetylcholine and they fit into the receptor and they push the button. And when the button is pushed, you get activation of the end organ. Note that with atropine, there's a little, I've drawn a little slot there so that it can fit into the receptor without pushing the button. The point is atropine can fit into the receptor and not activate it. The end organ isn't activated. The only, its main effect is to clog the receptor, to block it, to make sure that atropine or that acetylcholine can't get there. And again, of course, atropine won't fit at nicotinic sites, only at muscarinic sites. And you remember this. What was the problem with nerve agent intoxication? Effectively, too many green dots. And why did we use atropine? Because atropine was a competitive inhibitor of acetylcholine. That is, it blocked the sites. It was almost as if it were coating the muscle or the gland. Now, imagine that instead of having too many green dots, you have the normal number of green dots and you have the organ coated with atropine. What will be the effect of that? Decreased end organ stimulation. So, if the effects of nerve agent are end organ hyper stimulation, then what were those effects? In smooth muscle, for instance? In the eye, meiosis, bronchoconstriction, diarrhea. Okay, all of those things. And in smooth muscle, okay, in glands we had what? Secretions, sweating, lacrimation. Okay, well, those are the effects of too many green dots. What will be the effects of too few green dots? Just the opposite. So we're talking medriasses. We're talking urinary retention instead of too much. We're talking about constipation instead of hyper motility of the GI tract. We're talking just the opposite effects. We're talking about heat retention. Decreased sweating instead of increased sweating. And what do we say about heart rate with nerve agents? Is that a predictable indicator of intoxication? No, because it can do anything. It can go up and down. Now, if you just give atropine to somebody who doesn't have nerve agent on board, generally you'll get a tachycardia. But the nature of that tachycardia varies with the compound given. With atropine you get an initial brief tachycardia and then it's quite pronounced. With scopolamine, it goes up a little bit higher at the beginning and then it's really prolonged. It stays a long time. With BZ, you get tachycardia for a couple of days. And then as it returns to normal, the heart rate goes down to its normal and you may even become bradycardic. But if you don't know the time of onset of the exposure and you may not because these things don't give you any immediate irritant effect, you don't know what the heart rate, what information does the heart rate give you about this compound? Not much. So again, don't depend on the heart rate, just as you didn't depend on the heart rate with nerve agent, don't depend on the heart rate with anticholinergic to tell you very much about the compound. Now, the central effects, that is, the effects in the brain, in the central nervous system, they're qualitatively the same. Almost any anticholinergic will give you the same general kinds of hallucinations, the same general kind of stupor, but the dose varies. So for atropine, for instance, you're gonna need six to seven autoinjectors to give you marked confusion. Scopolamine, you need a lot less. With BZ, you only need one milligram to give you the equivalent of six to seven autoinjectors of atropine without nerve agent. And who knows what the dose for BZ is? Now, BZ, I mean, the dose for agent 15. So BZ, the official name is three, quenuclidinolbenzalate, that's my tongue twister of the day. And the reason it's called BZ is probably because the parent compound is benzalate, and perhaps also because of the buzz that you get, the high that you get from the injection of the equivalent of some atropine autoinjectors. The only incapacitant that the United States has ever weaponized, we started destroying the stockpile in 1988, almost all of it is gone now. If any is left, I'm not aware of it, but I'm not saying that there isn't some. And the point from this is that it's a solid, as we said before, the melting point is really high, so it's always going to be a solid. And it's extreme, it's odorless, you can have this, and there's no initial irritant effect, there's no initial behavioral effect, in fact you'll find out that the onset can be ours. So there's a latent period, just as there is with phosgene. It's also extremely persistent environmentally. So if this stuff is spread over an area, it can stay there and then it can be kicked up later by dust or whatever and still present a hazard. So it's usually dispersed as a solid, roots of inhalation obviously, roots of entry obviously inhalation is one, but ingestion is another, if the stuff is coating food or coating some other objects, or if you inhale dust and the ciliary mechanism brings it up to the nasal pharynx and you swallow the stuff, since it's a solid and it's very persistent, that's certainly conceivable. Or you can have absorption directly through the skin, especially if you have an adjuvant like DMSO that increases penetration of anything into the skin. We don't have a detector for this, so it won't show up on the M256A1 kit, won't show up on the M8 alarm, won't show up on any of these things. Now, what was the LCT50 for riot control agents? You don't have to remember the exact number, but it was pretty high, wasn't it? In, yeah, in the 60,000s, 100,000s, well, the LCT50 for BZ is even higher, 200,000, although it is possible to die from BZ primarily from secondary effects from hypothermia because you don't sweat anymore. But the ICT50 is fairly low, in fact very low, but look at the onset of effects. Half an hour to four hours, mean time of two hours, but it takes a while for the effects to come on. And when they do come on, and they may not appear until a day and a half after ingestion or inhalation even, but when they do come on, they stay for up to four days. And what are the peripheral effects? Well, we know the peripheral effects because they're just the opposite of what you've been drilled ad nauseam concerning nerve agents. So whereas the nerve agent effect on the eye is myosis, what's the effect of BZ on the eye? Medriasis, okay? Paralysis of a common day, okay, what are the oral effects? Since nerve agent made you wet in the mouth, what will BZ do? Give you dry mouth. Since, and remember we said heart rate was unpredictable with nerve agents, well it's unpredictable with BZ as well or at least it doesn't give you a lot of clinical information. GI effects, remember what were the GI effects of nerve agent? Hypermotility, so nausea, vomiting, okay, diarrhea. So what were the effects here? GI shutdown, constipation, decreased mobility, no utility, decreased secretions. And remember, whereas nerve agents can make you sweat, these agents will make you stop sweating, atropine stops sweating. And that can lead to heat retention, hyperthermia, and GI effects, nerve agents can make you incontinent of urine as well as the feces. And you saw, remember the monkeys, how many of you are monkeys defecated for you yesterday? None, that's odd, because usually they do. But certainly that can happen with nerve agent incontinent of urine. Well what's gonna happen here, urine retention. And of course, since nerve agents cause fisculations and twitching and hyperactivity of muscles, what will BZ do? Where does atropine not fit? Nicotinic receptors. So you can't automatically say that you're gonna be weak from BZ. Now it so happens that most people do get weak from BZ, but we think it's a central effect rather than a peripheral effect. Since BZ and its congeners don't really fit into nicotinic receptors, they don't really block acetylcholine at those sites. But centrally, you do have some incordination, heightened stretch reflexes, ataxia, and sensations that are perceived by the casualty as weakness. Okay, now the central effects are wonderful. That's the reason that it's fun to give this lecture, because of the central effects. You start off, I mean there's some general effects on level of consciousness. There's drowsiness and more sedation and stupor, and if you give enough of the stuff, you can induce a coma. But, and there are also disturbances in judgment. And so people will make decisions that are inappropriate and they will confabulate, they will use profanity sometimes. But the really fun part are the perceptual changes. Because people will have hallucinations and illusions from this. And generally, okay, how many have ever treated a psychedelic, somebody who's had a psychedelic overdose? Okay, tell me what those hallucinations are like. They describe their hallucinations as, I mean, alterations and just, they could hear sounds and see, they could see sounds and hear visual cues. Okay, and that's very common with psychedelic hallucinations. You get sensory crossover from one modality to another. And also, the hallucinations often tend to be geometric and abstract. You see weird shapes and all of this, and they don't have a lot of connection to the reality. The hallucinations induced by anticholinergics are extremely vivid and real. The patient identifies something. It's an elephant or it's a tank or it's something, but it's not there. But the patient thinks it's there. And often he thinks it's there because of the visual clue of something little. He sees the flag or he sees a wrinkle in the carpet. And that wrinkle in the carpet becomes a large boa constrictor to him. But he knows it's a boa constrictor. He may be talking to him and he may be talking back to it. But he knows exactly what it is. It's not some ill-defined mélange of colors. And those hallucinations tend to decrease in size over time as well. So somebody can be having the conversation with the elephant and a little bit later, the elephant becomes a rhinoceros and then the rhinoceros becomes a cat with purple eyes. But it's something very, very concrete. And eventually there's a nap or something. Tension and memory deficits, deficits of expression and comprehension. So we have, you know, sometimes the speech is kind of slurred and senseless and doesn't make a, and it's almost as if he's half asleep and he's concentrating not on you, but on the ball game that he sees in front of him. And he's watching that on the television in front of him. Where there's really no television, okay. So a disorientation to time and place. I mean, this may remind you of people that you know. We may remind you of some of the speakers out here. It may remind you of some of the review sessions. But we are, I guarantee you, we are not surreptitiously administering anticholinergics here at all. Even though your mouth may be dry right now. Mine certainly is. One of the particularly interesting characteristics of people who have been intoxicated by anticholinergics is that they, you know, the old expression will gathering. It's from gathering something that's not really there. These people will pick bits of lint that they see on your clothes or on their clothes, but they don't even have to be on the clothes. They're picking it out of the air. And what this seems to be is kind of an automaticity of, you know, basic actions that are repeated. And the disrobing seems to be partly automatic and partly a response to the impression that these people are too hot. So these people are really fun to watch and they're fun to talk to. And one moment they can be, one moment they can be completely with you and they know where they are. And the next moment, they're back talking to the boa constrictor. And that's also one of the characteristics. So if you see somebody who's there or not, so what would be one of the important tests to distinguish this kind of effect from, say, anxiety or just confusion? What kind of exam are you going to do? Now let's see this exam. You're going to say, are you oriented to time, person, place? Can you do serial sevens? What's your short-term memory? Who is the president of the United States? People who are anxious and are having panic attacks can usually remember those things. They may have some deficit in serial sevens, but usually they can remember those things. People here, not only will they not know the answer, if they don't know the answer, they'll make up a great one. They can fabulate. Who's the president of the United States? Oh yes, it's George Fitzpatrick, yes, and his vice president, and they can go on like this, creating something that isn't there. Behavioral liability we talked about. And the other interesting thing is that as these people are coming out of this, all of a sudden they kind of realize, they begin to realize that what they thought was real wasn't, and then they get really paranoid, and that's when they really need to be restrained. And most of these patients actually will require restraint. Most people actually go through four relatively distinct phases. They slide into one another, but with the onset of a little bit of drowsiness, some mild CNS effects, some mild peripheral effects. Stage two, and that may not begin for four hours after exposure. It may not begin until much later if the onset is later. But then in the next page, they get really unable to walk well, and they may heat up because of lack of sweating. In other words, the peripheral effects become more pronounced. And here's where it is the most danger from dying from heat stress. And in the third place, in the third stage are the fluorid delusions, and eventually they sleep this thing off with paranoia in that phase also, as they're going to sleep and waking up. Now, I think that the two most useful slides in this lecture, or the slides that you're seeing right now, because when you see somebody with hallucinations, or somebody who is acting funny on the battlefield, what could it be? Or somebody who's acting funny in your emergency room? What could it be? Well, there are plenty of things that cause what you see in the first paragraph. Restlessness, whiteheadedness, vertigo, the stumbling or stagnating, vomiting, anticholinergics will do it. Psychedelics will do it as well. Marijuana will do it. Alcohol can do it. But specifically, anticholinergics will give you this combination of central and peripheral effects. The hallucinations plus the dryness of the mouth, the urinary retention, the heat retention. And you'll have these, you know, you may have, classically, you may have these phantom behaviors of picking and mumbling, that kind of thing. You may not, the patient may not have a classic presentation, but classically, this is what happens. Now, what happened? How's that different from psychedelics? Well, remember, the hallucinations are a little bit different. They're more abstract, they're more geometric. People also are often, you know, inappropriately happy with psychedelics, right? Those of you who've treated psychedelics sometimes. Unless there's a really bad trip. And there may be some peripheral changes, but they're not usually, except for occasional medriasses. They're not the ones that we traditionally, that we characteristically associate with anticholinergic overdose. Now, marijuana, again, marijuana intoxicating, you know, people under the influence can be very, very mellow. That's a good term to use. And these people are, you wouldn't really describe an anticholinergic patient as mellow. He's more self-absorbed, and is on hallucination. It's not quite the same thing. And of course, with an anxiety reaction, you can, you know, sometimes people lose the loss of a limb. They can become apparently blind, even though their eyes are open, although that's a rare reaction. What do we call that? Conversion. A conversion reaction, okay? So, the differential diagnosis here is something that I think that you ought to keep in mind. Now, how would we apply asbestos to something, well, you know, if our differential diagnosis led us to BZ, then we'd immediately think, well, what's the state? Well, we know it's gotta be solid. What does that have? What implications does that have? Well, it has implications for decontamination. It has implications for stirring up the stuff if you think the guy's covered with it. You don't want to inhale it either. Inhalation will be the probable root of entry, but be aware that there are other potential roots of entry. Do are the effects local or systemic? Systemic. That's what we worry about. We worry about us getting to the CNS and producing the hallucinations and getting to the peripheral end organs and causing hyperthermia, causing the other effects. Okay, and this kind of thing. Okay, treatment. Always, always protect yourself first. And then if there's general supportive therapy, well, you can do that. Well, the general supportive therapy here obviously is decon and soap and water's fine or brushing for clothes. Observation and, you know, most of these patients, as I said, really will require restraint at some point. When that probably also means early evacuation because they're gonna be in your way. They're gonna hinder you unless you restrain them and put them off to one side and it would be better even if you could just to get rid of them. Because their course will be prolonged. They're gonna be like that for three or four days. And in fact, nothing we have, even specific antidotes, nothing we have is going to change that. The antidote we have is something that will control the symptoms while they're there. But if you stop giving the antidote, the symptoms will recur. And what's the antidote? The antidote is, well, let me ask you. Let me back up and ask you this. Since the effects are those of atropine and atropine is used to treat nerve agent, what would be a good, and nerve agents are anti-colonesterases, what do you think would be a good category, a good candidate for an antidote to BZ or to Agent 15? Nerve agent. Nerve agent, you mean you want to treat these people with nerve agents? As a matter of fact, animals intoxicated with BZ have been treated and treated successfully with VX. Now I'm not suggesting that you carry VX to give, but you understand the rationale. You can treat an anti-colon, that is you have too few green dots. And what do you want to do? You want to make more green dots effectively. So if you administer something that's an anti-colonesterase that cuts down on the destruction of the green dots, well, you have more green dots. That's what you want. You want to increase the effective level of acetylcholine in the synapse and at the neuro-glandular and neuromuscular junctions. And the one that we use, that we tend to use is physis stigma. And physis stigma is nonpolar, so it crosses the blood-brain barrier. Do we want that? You bet we want that. Remember periodostigmine doesn't, under normal circumstances, cross the blood-brain barrier. And we don't want it to cross that because we don't want central effects. We don't want confusion. We do want this to cross the blood-brain barrier because we already have confusion and we want to get rid of it. And, you know, minimally effective during the first four hours, that's characteristic. If you had somebody and you knew that he was hit two hours ago, you can give physis stigma and typically there will be no response. But beginning at about four hours after onset, physis stigma is very good. And I realize I haven't put a dose up here, but the dose is usually about 30 mics per Kig, which translates to 30 to 45 mics per Kig, which translates to about one to two milligrams in a 70 kilogram person. Give that intramuscularly, IV can be dangerous for some of the same reasons that atropine given IV as a bolus can be dangerous. Precipitation of cardiac dysrhythmias. But you'd give one to two milligrams, re-evaluate, I mean, give another dose in 20 minutes if you needed to, and then re-evaluate in probably every one to four hours, you'll probably have to give more physis stigma. But you'll have to do that during the entire course because once you stop, the symptoms will recur. Side effects are cholinergic and you all know, how many of you have used physis stigma in clinically? Okay, so you know it's not something that you use with careless abandon. There are some significant side effects. So if these patients really do appear to be getting better or if they're not severely intoxicated, you may elect not to use physis stigma at all. But if you do use it, use it with the cautions that we've talked about, and what would the side effects be? They'd be cholinergic, wouldn't they? Because physis stigma is an anticholinesterase. So, what's an incapacitant? It depends on what your definition of incapacitation is. The specific definition for this particular class is a class of non-lethal chemical agents excluding the riot control agents because technically we don't consider them to be a part of this, although they're designed to accomplish the same thing. The incapacitation is normally derived because of the CNS effects, although there are peripheral effects as well. Only known weaponized agents are BZ, which we have, and Agent 15, and we're not exactly sure what that is, although it appears to be a glycolate anticholinergic, either identical to or similar to BZ. Delayed onset, okay, also occurs as a solid. Delayed onset, protracted course, up to four days. Labile presentation, the sensorium goes in and out, the hallucinations go in and out. Remember the combination of central and peripheral effects when you're doing a differential diagnosis of this, and the specific antidote is physis stigma, and that's all I have to say about anti-incapacitating agents, and if you're not completely incapacitated, you may ask questions. Sir, you said that if you stopped the treatment with phyto-stigming, that the symptoms and signs tend to recur, yes. Will they come back at the same strength as they were before you started the treatment, or will there be any decrease at all, or? No, they can come in, and in fact, if you use phyto-stigming and then stop it, the clinical course tends to be prolonged. You tend to prolong the clinical course. So once you start it, you want to stay the course with it, but yes, if you stop it, the clinical symptoms can come back full-blown, just as full-blown as they were. Once the pharmacokinetics are such that you've got, you've got no more phyto-stigming in the system, the symptoms recur. Yes, ma'am. I was wondering, you were talking about BZ degradation, or you were talking about BZ remaining in the, yeah, how long does it remain in the environment? Does it break down? Do we know this? The studies that I've read indicate that it can be around for a long, long time, and part of this is the fact that it's just a very stable, the crystalline structure, et cetera, and the fact that its solubility characteristics are such that it just doesn't seem to break down in the environment. It's one of the most stable chemical agents that we know of. Now, we already know that mustard can stay around for how long? Months sometimes, okay? This probably can stay around almost as long or maybe even longer than mustard.