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this on the information Doctor Siris. My name's a Ube Osmond. I am one of the co founders of the six PM Siris on. I'll be doing the first session covering today, which will be based on anesthetic pharmacology on. I've talked this twice before. Believe on dive made this electric slide with the help of a niece. This is currently a Reg Dysuria and his name's doctor, Alec Beanie. So, uh, thank you to him. So just to start off with the usual stuff. So if you haven't already joined our social, please drawing on social, we've got an instagram page Facebook page Twitter page, please, if you have enjoyed him, because it's how we keep you up today about what New Siris will have going on throughout the year. And it's also where we post questions on its content, where you can sort of console late and revise. Your learning on is also orthopedic sort of miniseries going on the moment being run by she hair in the set of former videos, so make sure to follow our social. 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You've got analgesia, which are pain sort of numbing medications of these pain relief medications, because if somebody is going on operation, they're gonna need lots of strong pain relief because someone's cutting open into them through different places, and we've got muscle relaxants which helped the sort of paralyze the body specifically the vocal chords. And this says specific to when a patient's going to be introverted because you don't want focal chord spasms. Because if someone, if you try to interpret somebody without a muscle relaxant, you irritate the vocal cords before you enter the lung. And that means that could potentially clothes off the airway and cause a whole lot of issues down the line. So that's why. And when we choose to intubate somebody, we get muscle relaxants. But other sort of drug groups that are important in terms of pharmacology in anesthesia and sort of general medicine, I'd say, are things such a sedatives vasopressin, which is a bit more specific to hate, to use anesthetics and the intensive care unit and talk a little bit about those later and then sort of university useful antiemetics. So we're going to start off with the first question. So your nephew, one who is attending the emergency fatalist with a consultant any cysts? A 22 year old gentleman is being rushed in because of a ruptured appendix. They have no medical history, they've got no drug allergies, and I've got no relevant family history, the nicest tops for a rapid sequence induction and uses an agent which causes the patient to for sickle it. So which muscle paralysis agent was used and we'll put up the pool. Okay, Brennan. So Savella looks of the majority of answered correctly, the correct answer Socks? Um, a phony. Um, for those, you know, particularly Eagle I did have been to my previous elections before she recognized this in particular. You know, that is sucks in a phony, um so in terms of sucks on the phone, and it's also called seasonal choline on. That's because it looks like two acetylcholinesterase molecules band together. So what it is, it's It's a depolarizing muscle relaxant, and it's used in a rapid sequence induction, and I'll keep it simple about what our site or rapid sequence induction is. It's a type of anesthesia that you do when it's an emergency or when a patient hasn't been starved and I'll keep it as simple as that. But there's obviously more things involved in our and what a depolarizing muscle relaxant does is when it binds. It causes sort of action potentials to propagate across the muscle and it acts that you like a seat are choline, but it irreversibly by a reverse to be buying so causes muscle contraction and how you see that when you give saxophone, um, in and acts, it's It's in the form of global muscle for circulation to see, although muscles contracting particular. You're looking at the end of the bed and you're managing the airway you take. You see the legs spasm or the arms, and you'll see lots of for circulation. And that's when you know that a patient is ready to be intubated and you know that they're paralyzed on as I've mentioned, it's structurally similar to to acetylcholine molecules, which is why I combined to the same receptors. But it does so irreversibly so in terms of the other agents that all none depolarizing so they do not cause muscle for circulation's, and they also reversibly bind. And the only other, none sort of depolarizing muscle relaxing that's also used in rapid secret inductions is rocuronium, but at higher doses. And it's an anti seizure, I think, across sort of the country that increasingly moving towards using rocuronium compared to saxophone you because of all the issues that come with sucks. So, as I've mentioned, sucks, um, finding structurally is to a seat on Coney molecules bound together, which is why can cause depolarizations on it's non competitive. As I said, it's irreversible. Binds to the negative nicotinic acetic allergic receptors, which is the ones they're involved in. Voluntary muscle contraction, specifically skeletal muscle we're talking about here on depolarizing, meaning causes muscle for circulations. It's metabolized by your sort of plasma Coney Nest razors. And when somebody has a deficiency in a plasma Corey necessaries, that's what puts them at risk of, ah, severe complication called Saxenda phony um, apnea. And that's these patients that you're trying to wake up. But they remain paralysed because the body isn't able to metabolize Suxenda phony Um, as a normal person would, because this cholinesterase deficiency, which is quite serious and it may mean that they have to be interpreted for for a longer period of time for the saxophone, you to wear off and that could be inherited. Or it could be acquired. So in terms of side effects, because it causes muscle for circulation's, you could imagine that you're exercising and your muscles are twitching and moving around it's going to actually cause you know, someone to feel a bit sore afterwards. It causes hyperkalemia because of those muscle contractions, because the quite strong muscle contractions and it's a whole body contracting. You get some leakage potassium from muscle cells and that leaks into the bloodstream so as a potential to raise your potassium levels up a bit. Which is why you need to be careful in patients with, you know, AKI. All patients that have, you know, multi trauma spinal injuries, burns because these patients are more likely to have cell license and destruction if they're contracting. And they're going to more likely release higher months of potassium from cells. Which is why it's a country indication in spinal injury, multi truma and bands patients. It can also cause racing, talking it pressure, intracranial pressure, ready mentioned sucks apnea. And another severe complication is malignant hypothermia, which I won't be covering today. But the important things to consider is a history of subsets apnea, sort of in the family. That's why you typically ask anybody had any issues, any anesthetics in the family. So, apart from postoperative nausea, you also asked specifically about if anybody had any trouble in regard to sex, sex apnea or malignant. I prefer me a previously So let's move on to the next question. So Urine F one who is attending the elective gynie fatalist with a consultant in the PSA test, a 54 year old lady is undergoing an elective laproscopic hysterectomy, nicest tops for fentanyl, propofol and muscle relaxant induction. Which muscle relaxant was used almost like it was most likely used? Okay, bring it so the drug TV correctly. The correct answer is atracurium. So in terms of security already mentioned, it's it's type of none depolarizing muscle relaxant. Anything that ends with our eye, um, is typically in under the polarizing muscle, relaxing an interesting fact. So I believe it's from sort of in in Brazil, specifically in sort of specific tribes. Some tribes used to use sort of a form of atracurium in their poison darts to for hunting because it used to paralyze animals. And that's how it was discovered. Eso atracurium is typically, and any other sort of Monday polarizing sort of muscle relaxant are typically what's used elective anesthesia of someone we've solved. The patient, you know, appropriate that all the drugs it's not an emergency, basically on a 10 to be safer and reversible, which is why we want to use sucks in our size because it has advantages. But it also has many disadvantages. Glycopyrrolate is a muscular Rennick anticholinergics. It's used with new sticking, different brother cardio and you stick me being a reversal agent that we talk about little bit later, as I mentioned, Sucks and Falling is not used an elective surgery, only using emergencies. Specifically, we're talking about rapid sequence inductions where patients haven't been starved and it's some sort of an emergency, and ketamine can be used. But it's used in our size and it's morula, I would say, Actually, in pre hospital medicine, I'd say it's specifically with sort of big trauma accidents particularly useful in hemodynamically unstable patients, because it's a bit more of a cardiovascular stable anesthetic agent. But it's not a muscle relaxant. It's a unconscious sort of anesthetic agent little bit about this sort of thing receptor between sort of the neuromuscular junction, because lots of things act and always think it's quite useful to think about. So in terms of Presynaptic Lee, you know you've got a visa. Calls of a seat up coding. They get released. See the colon binds to the muscle receptors, sort of postsynaptic in the muscle. So right receptors. And that's what causes the stimulation of muscle contraction at the's nicotinic acetylcholine receptors involved in skeletal muscle or voluntary muscle contraction. So what none depolarizing muscle agents do, such as atracurium is they reversibly bind to these receptors, but they're none depolarizing. They don't propagate in action potential cross these muscles, and that's why it doesn't cause for circulations on it. It sort of it competes with a CT coding. So again it's ah, it's zero first walked. That makes sense. So saxophone. Um, on the other hand, there's two acetylcholine receptors bound together, irreversible buying stress receptors. And it's called the Depolarizing muscle relaxant because it propagates in action potential. And that's where you see for circulation. And that's how we know in on our if I when we've given them Suxenda phony, um, that when they're ready to intervene because you see all those muscle for circulation's, and then we'll know that patients paralyzed on as I've mentioned plasma cholinesterase is on what's important in terms of breaking these down, and when you have a deficiency of thes in gets sucks apnea. Interesting. If I have to talk about my favorite family of pretty nutty a favor family of back here, probably the close change your family because so many so many bacteria are recalls really serious infections involved in the classroom. Very one of the MS Tetanus that we're sort of, you know, vaccinated against chickens. Young Children so see, technique toxin can sort of presynaptic. We travel and destroy nerves, but you're sort of questioning botulinum stops. The release of the seats are calling so it can cause this flaccid paralysis because you're not able to research see their coding. And that means you can't contract your muscles, which is why it's used in Botox because Botox helps relax muscles. You've got neostigmine that we talked about earlier. Which is that reversal agents on? Was it? What it does is it stops, stops. Acetylcholinesterase is essentially organophosphate. Poisoning is another thing that we need to think about. So organophosphates taken bind to ah, cyclical less raises and inhibit them, and they can cause a sort of titanic paralysis. For that reason, because you got to remember, these cholinesterase is break down a seat. How choline molecules and need sort of stopped contraction happening. So when you get a gonna force vaporizing, unlike but in any in prison, instead of a flaccid prognosis, you'll get a a sort of, ah, Titanic, more of a you know, you get you get more of, ah, a contracted sort of paralysis because of the access acetylcholinesterase around your body. So that's have been little look so just for energy. And I said in perspective and pedal in a little table. It's all the things that have already mentioned. So just again to mention that sucks in formulas. None reversible, only using our size. Atracurium has reversible binding in cause paralysis, but there's no fasciculation because it's none depolarizing neostigmine being a reversal agent, and it's used in elective anesthesia. We've got rocuronium, which is another need. Polarizing none. Depolarizing muscle relaxant can be used in elective on emergency surgery because they said in higher doses it can be used in our size, and it's what I think anesthesia across the country is more moving towards is what I believe on. You've got a more specific reversal agent, which is much more expensive for it called Sugammadex, which is like this ring, sort of sort of binds around, is the best way to explain it. And that's a specific reversal. Agent to rocuronium on. That's another one to remember. I'm just going to quickly could the chat make sure that somebody hasn't asked me questions. How much you have to know about? I come back towards those questions towards the end Guys on. I think Sufi so s if he is ready, answered some of those. So let's move on to the next question. So you're on F one who is attending the elective gynie fatalist again with a consultant. Any cyst? 50. It's a 54 ladies on the golden elective like prescribe crickets. Director. Me. The patient is currently hypertensive following sort of anesthetic induction, and the blood pressure's is 70 systolic 30. Diastolic and I have a heart rate of about 70. So the nieces administers the medication through a peripheral cannula. Which drug did they likely administer on? Let's put the pole up. Thank you. So that's a really good with the majority of your on. So this was again a trick question. I think people have fallen to the same sort of pit because of what they probably recognize the majority of the insulin or adrenaline, which is the incorrect answer, and people have been attendant previous. Select The correct answer is metaraminol talk a little bit about Why so a metho Um, it'll on average rid or women very commonly used vasal process least in the UK during anesthesia, nor adrenaline, which is what most you picked your correct. It's a very powerful vasopressin, and you probably would have come across that many times. In the intensive care unit, however, it is usually given for a central line. The reason being is because it's such a mixed evidence on this, but the practices to put it for a central line. The reason being is because it's such a powerful razor prostate. If you put it somewhere more peripherally, it can cause. So it's such a basal constriction it can possibly cause scheme era of the lymph below it. So that is the theory and the reasoning behind, and it's typically not the first line basic price of that we use, um, either, but a good four, and it definitely is a very powerful, very suppressant, but it's metaraminol. That's usually first line now problem with Metaraminol is that it can cause this reflex bradycardia. So if a patient was hypertensive mbradley Codec, you know you'd be considering other things. Where, There, you know, whether they're bradycardia, consider atropine and a few other things. But you wouldn't give Mataram in Oh, because it can potentially lower the heart rate even more so if if the heart rate slow along with the BP, you'd consider giving something else if it's related to the anesthetic. And the important thing about Metaraminol is, which is what I'm sort of trying to get forward in a vineyard as well as it can be given for a peripheral line. Unlike a nor Drennen, at least in UK practice and in terms of effort drink that's using you second line. And it has, you know, I in a tropic so sort of iron atropic, meaning in terms of strength of contractivity of the heart, or how well the heart contract and chronotropic meaning sort of rate crow, no meaning time so it can increase heart rate and contractility, and therefore it's useful in patients that are hypertensive bradycardic, where you wouldn't up to use metaraminol. But if the body Codec really broader card. If you could also consider atropine, depending on the course that can also be given peripherally. And atropine is a muscular neck. Article in Ergic is used in significant bradycardia is with hypertension but not used for managing low BP alone. So one of my favorite diagrams that I always like to go through because I think it nicely explained sort of the autonomic nervous system. So if you remember how the autonomic nervous system it split it split sort of in terms of the sympathetic and the parasympathetic nervous system, sympathetic nervous system we talk about, you know, this fight or flight response, and the parasympathetic system took about sort of rest and digest to keep it very simple. But it's obviously more complex than that in terms of the sympathetic nervous system, remembering where the nerves come out from. What I remember is the part of the spine is for a colon, but it comes out in the Focalin despise so sort of the thoracic spine and the lumber spine. And if you remember for a co is the first word and lumber, it's a second word. Um, it's a sympathetic nervous system ranges from T one lt because for a copay meaning one lumber meaning to And that's how I remember where my sympathetic nerves come out from. In terms of the autonomic nervous system, it comes up from above. A lot of cranial nerves have autonomic functions, specifically person synthetic functions specifically, or 10 being the most famous one Vegas. Meaning the wondering Now because you know that's involved in your digestive system, your heart rate, you know, a lot. A lot of your vagus. Never, you know, goes practically everywhere basically. And then, you know, you sometimes have secretary functions from the saliva glands from somebody's s O. There's lots of sort of person frantic activity from those sort of cranial nerves in particular. And moving a little nervous system and then going below, sort of into the lower lumbar spine and the sacrum. If you remember, s 234 keeps your stuff off the floor or keep it. PG this time round on the free pizzas, poopy procreate, dental nerve coming from that area. That's the sort of things that that sort of bottom area of your system nervous system is related to. Now, when we're talking about sort of receptors and sort of adrenergic receptors because that's typically we were talking about when talking about the sympathetic nervous system, with one rare exception. Being sweating, which I'm not going to talk about out for one receptors is what you want to remember. They're involved in vasal construction of blood vessels, so that's one when we're giving a vasopressin. That's what we're hoping we do, hoping to vasal constrictor blood vessel with the aim of increase in blood pressure. Because of that, because of the formula that I'll show you on the next slide, um, Alpha two receptors on more than a basal motor center. So you remember you've got this barrier receptive reflex specifically in your carotid arteries, a Z well, assort of the top of your aorta. You've got the Barrett's tough is that since pressure and then he sends too much pressure, they send signals sort of down the nerves to the vasomotor center. Acting on specifically does sorts of receptors, and that means they try and slow your sort of heart rate down to try and lower your BP in effect. So that's embarrassing up the reflex that we're talking about that. Beat a 11 because you've got one hot. So be sort of be two blockers and stuff, you know, decrease your heart rate day, typically acting those receptors. But it also act, um, beats, too. So beats two receptors meaning to you can remember for lungs. So things like, you know, so beautiful being the most common thing that I remember my head right now, open up your airways when things buying to it. They cause, you know, bronchodilatation. And it can also act and other types of smooth muscles and beat the free being related to sort of like policies and fat metabolism. Eso, as I've mentioned metaraminol, can cause reflux cardias to make sure heart too slow and ephedra and habits northern every uptake. So it's kind of like a week in or Drennen. But so, and that's what each of these sort of drugs buying too soon order in a very powerful vasopressin accent. Alpha one mostly and Alpha two is well but has very weak beat. I get sort of be two agonist IQ effects Mataram in or is it depends on the text books you look at purely for the most part, on Alpha one receptor agonist. So mostly causes vasoconstriction alone on Effient has a mixed the effects because it sort of prevents nor general reuptake. And it also has, um, Alpha one activity more than Nordgren Lynn does fine and just very quickly talk about this equation. So BP or most definitely mean arterial pressure is equal to cardiac output times your systemic vascular resistance, which was talking about some of the systemic because you have your pulmonary circulation and your systemic circulation is talking about the resistance in the blood vessels in the circulation's and sort of how constructed those blood vessels are. And when you're affecting alpha one receptors, were you giving something to sort of Actonel form receptors? You're trying to increase the systemic vascular systems to try and increase the mean arterial pressure, the whole point during of anesthetic to keep the BP office to make sure that we perfusing the brain and all the important organs. That's why BP and mean arterial pressure and why we serially monitor observations are so important. Chronic upper is equal to stroke volume, which is the amount of blood that your heart pumps out with each beat times your heart rate on beat. The one agonist, um, acts on that which is discredited. A cone chronotropic why we sometimes get beat a blockers and some pages, such as patients with fast they after trying to slow the heart rate down and then the stroke. Volume is affected by lots of factors, including preload. How well and how much returned your heart is getting from the sort of right sort of sign of circulation contractility, which is very high in atropine, which beat the one receptors act on and after load after notice. Sort of. The easiest way to think about is how hard your left ventricles having toe work to push blood out fruit it aortic valve into thesis temic circulation into the aorta. And one of the things that can affect that is safe for patients got really high BP. That means the afternoon is much higher because patients pump home after much harder in hypertensive patients and work much harder to try and get blood from because of that higher after load, which is why patients with uncontrolled hypertension can get, you know, left ventricular hypertrophy because the heart's going to work extra hard and eventually, you know, need to weaken in the muscle and potentially heart failure. But we'll leave that fine. And this is this the table to talk about everything that I've already mentioned. Just make it nice and easy. Um, fine. So, uh, let's have a little look. So we're going to move on to the next question for the sake of time. So you're a 50 year medical student attending a placement, and I see you, a 24 year old patient is currently being intubated and ventilated following a hypoxic cardiac arrest. You to a drug overdose? Um, he currently has a pro pro for infusion running. How does propofol work on if we put the pole up? Please, Let's have a little look. So the majority answered correctly. So it's it's it's It's gaba agonist. Um, so, in terms of the brain and times of sort of the main inhibitory sorry in terms of the main inhibitory and sort of accept excite a tree neuro transmitters. So the main sort of inhibitory nerve transmitter is is sort of GABA. Which one's the GABA receptors? Obviously, in the main excitation know, transmitter is clued in eight, so the GABA receptor is sort of implicated in many sort of drugs, is what I'll say. So I'm not gonna mention or even, but so benzodiazepine is being the main one. Propofol also acts on GABA receptors, so the more you stimulate GABA receptors, the more so neurological, depressed, sedated or unconscious a patient will be. That's what benzodiazepine they're used, it says. It's it's sedatives. That's why you know, propofol is used to make patients unconscious because it acts on the scab. Subsequent barbiturates also do the same thing on in seizures. You gotta think eso another example coming with seizures when it's too much excitation going on you on a slow everything down, give benzodiazepine sort. Of course, GABA again is, um, to cause neurological depression on to sort of make people more sensitive, relaxing unconscious and to reduce brain activity, which is why it's useful in seizures. But also, if you think about alcoholics, alcohol acts on the GABA GABA receptor as well, and in patients that get out called, it's ah, alcohol's sort of the president is what they call it. So, you know, neurological depressant specifically is what I mean on, you know, when patients have, you know, history of alcohol access and, you know, whatever my units, that drinking and you've been drinking for a long time when they go into a drawing and they lose that neurological depression that was given to them by the tons of alcohol they've been drinking, they become an increased risk of seizures. Which is why we put people on sort of the sea. While scoring is what we call in the UK, which is related to sort of when we think someone's an alcohol withdrawal, because we don't want them to have a seizure secondary to alcohol withdrawal. And the treatment for that is chlordiazepoxide, which is in the UK at least, which is a type of benzodiazepine. It helps them with this sort of withdrawal from our course. So that's another way of thinking about government. That's why knowing about the governor receptors important not just in a seizure but in general medicine is what I'm going to say. And India receptors where glutamate bind so really mention it to the main excitatory nerve transmitter into target of sort of a few dementia drugs is when there's ketamine and Katarina of also mentioned is a bit different A. Z. Well, it's also another Asian that we used to make people unconscious. But instead of act on GABA, I'd accent and NMDA receptors. Serotonin antagonise are often the targets antiemetics, which we'll talk about later. Some antipsychotics and anti migraine medications also act on it, and dopaminergic antagonised are sort of target of, you know typically don't magic receptors on the target of Parkinson's or antipsychotic or anti medication drugs as well. So we took a little bit about that later on as well, so very quickly talking about proper force. A probable enhances the effects of GABA eso at lower doses that commute for sedation. So, in a sense, sedation. There's plains of anesthesia that we talk about. So there's a pain where you're sort of all the way unconscious, the way you're a bit sedated, and there's a bit in between where you've lost your airway, but you're not fully unconscious. If that sort of makes sense, so the planes is what I'll leave it up antiseizure on. Depending on how much you give, you can make them fairly unconscious and any style or, you know, given sedation. One example that I can think of insulation. Where we use it is when was shocking patients out of rhythm. So we had a patient with That wasn't fast f who was within the 40 hour limit. New onset new one there onset was well, so we had exactly mount of time. Make sure they were anticoagulated for they trialed some medications and see if anything, reversible for the F and then because it didn't we put them on the seat on emergency less the next day on day was sedated using propofol, and then they were shocked. And then they came out of it. So that's another sort of weight. It could be used and then things to note, but I'm not gonna cover it. If you have the chance, have a little bit about read a little bit about proper for infusion syndrome. It's particularly relevant in intensive care, where some patients say that for long periods of time and when they intubated and neither lots of propofol, they're on the for long periods of time. The propofol. Because it's such higher months doses, it can cause what's different side effects, and it also reduces systemic vascular resistance. So if a patient is hemodynamically unstable, you typically no opt for propofol you up for something else like cattle me? Because because it reduce the system and vascular system if patients already hemodynamically unstable. And by that I mean low BP, higher heart rate, you're going to lower their BP more and then potentially affect their cereal profusion and cause, you know, hypoxic brain injury because of like of cardiac upper, since she at what lack of mean all to your pressure too profuse The brain, if that makes sense in terms of benzodiazepine, is also, you know, as I've said, enhanced effect of GABA. And it increases the frequency of open cross channels, community sedation or anxiolytic so treatment in seizures. And it's also treatment organophosphate poisoning, barbiturates. We've talked about similar thing enhances effects of Gabbard. The increase in duration of chloride channel opening, also using on the seizure, also used anti epileptic medication and that central line, but is wrong. Ignore that. Apologies for that could be given for a purple line as well. Fine. So, uh, let's take a fairly second one minute break should we say just so I can catch my voice and I have a little like a chat to see if there's any questions that somebody wants me to answer. Yes. Disregarding. So this'll recording will be available on metal, as all content will be. So make sure to sign up for Medicare. And is there any questions, guys? So far, um, I'm going a bit too fast or are you able to follow along? And remember, even if you can't, the recording will be available. And we also have the slides available on metal to download as well. Okay. Thank you, Gina. Thank you. Um, yeah, we can we can POSTOP the we compulsive, the medicine fear. Would you be able to post stop the metal feedback link case for anybody that wanted Teo leave a bit early, But yeah, I do that now. Also got a question about the relevance of fascicle asians. Okay, fine. So specifically when we're talking about for circulations in the relevance of muscle relaxant. So let me cook a little bit about I guess so. When we decide to operate on something, there's a few factors that you need to take into account. S 01 is the length of the operation, which is very obvious airway difficulty and a few other things. But let's talk about length of operation. So typically, if it's an easier way and it's a short like from operation and they say less than an hour, you could do something like Ellen. A. So in elementary beaning allows your mosque, which doesn't go through the vocal cords on. That would mean that you don't have to give muscle relaxants now if the operation goes on for much longer period of time or it's a it's a very difficult operation or it's a difficult airway. You can opt to introduce it, but there's obviously other things in between. I'm not going to talk about everything, but when you're up to intubate, you have to use a muscle relaxant, as I mentioned. And because the vocal cords are very sensitive to being touched on diffuse, imagine that somebody tries to put a tube down your vocal cords. Only you're gonna gag if you're not only, you know, paralyzing unconscious. Your vocal chords are also gonna spasm, called vocal chord spasms. And because of that, I can close off the airway, cause swelling in that area and potentially mean that it's going to be a lot more difficult to interpret if that makes sense and it can make the patient hypoxic in that time. Eso That's why we give muscle relaxant specifically with intricate. And when you choose to intubating give the none depolarizing or the depolarizing muscle relaxant the depolarizing muscle relaxing. The only one that I know of, that we use this Saxenda phony, um, and socks. Um, if only, um, only use an emergency surgery specifically and the relevance of the physical a shin started long story short is when you give socks and a phony, um, specifically a depolarizing muscle agent when you've given it, you know, when it's working, when the patients for second thing and all their muscles are moving about the kind of twitching on the bedroom literally see it from the end of the bed. One they've off. They finished all the twitching and all the physical issues that relaxed, you know, they're completely paralyzed and a means, you know, the vocal cords are paralyzed, which means they're ready to interpret. So that's the relevance of fasciculation specifically to sucks. Um, if only, um, in anesthesia hope that makes sense. Nickel on dressed of you, I guess, is Well, um, Okay, fine. So, uh, for sake of time, let's move on to the next bet. So your fifth year medical student attending an elective urology less. A 62 year old gentleman is undergoing a rigid cystoscopy and jury for biopsy on the general anesthesia. He has a pro. Sue Ellen, a lounge. Your mask, airway inserted would see the fluid, which is a type of heart and sort of gas as maintenance with a good back. I won't talk about what mean Elavil A concentration is but just stored away and have a look. If you're interested in that during the procedure has hardly increases from 70 to 90 on his BP increases from 160 to 130 over 90. He looks sweaty and his pupils are dilated. And HCG shows no acute changes the Unisys to administer the medication, and the signs resolve Which receptor does this drug act on? Yeah. Sorry. Just seen a apologies. So, um, the majority of you answered D which is muscarinic receptors, and it was kind of a trick. It was kind of a trick question. I can see why you guys did that because it's it's a sympathetic over activity. But it was kind of a trick question to you Was just trying to The simple answer is they've given him, uh, opiates. They've given um, or analgesia. So specifically in surgery day, we're least in the UK. I can only I contacted morning speak for the UK Really the use fentanyl, which is a type of opium which is administered, you know, obviously, to get pain relief during surgery so often most often when a patient gets sympathetic overactivity from all those signs that you've mentioned, the most common thing or the first thing in the list of things to think about is pain. Eso they often Often what you'll see is you see these patients, you know, with all the physiological signs of there in pain with sympathetic over activity, and we get a better fentanyl. You know, BP comes back to normal little bit. You know, the sweating is goes and the people's go go go a bit of a bit smaller size as well, because the pain has been relieved in the heart rate goes down and the BP comes down. It's quite it's pretty cool to see, which is why I like anesthesia, because this sort of instant physiology now I can see why you guys were thinking of muscarinic receptors. Drunk fritters, appetite, tripping produce the opposite of fact. That's in fact, none of the system. But that would be masking the issue that causes sympathetic symptoms in the first place. If that sort of makes sense, Thea other thing that's important to think about is sometimes patients are at risk of getting heart attacks in my eyes during a seizure as well, which is why the E. C changes are pretty important as well. So that's why the EKG was so important to make sure this patient wasn't going for an MRI during surgery and GABA receptors. So, you know, as I've mentioned, they're more involved in sort of alter unconscious level, and they're not typically used for pain relief. So I won't really help with that. And, you know the Kappa Opiate receptors, another subtype that has allergies effects. But producers are the side effects, such as dysphoria and some other other things as well, and it's it's it's. It's much more rare to see those drugs being used. New opiate receptors is what you commonly know, where your common opiates buy into that You'll know, you know, morphine, codeine, oxycodone, fentanyl, you name it. It's going to be the new opiate receptor that's come back on the cab. Okay. Tricep is a bit more rarer of a subtype and a bit more need eso have a simple answer is opiates. But as the first thing and then you need to make sure you look down, the less the things to make sure you haven't missed things. So just common drugs to know. I guess our codeine, which is a type of prodrug a pro drug meaning a drug that's in an inactive form until your body level, or whatever it is metabolized a specifically for the C Y P Judy six enzyme system in the liver in Codeines case. And then it gets sort of active day metabolized into more morphine. Codeine, interestingly, has such a spectrum of sort of attack. Um, ahem. A matter is a shin, depending on sort of what subtype of activity you have in this particular enzyme system. So Coney works really well for some people. We don't need the tiniest amount of codeine to get pain relief for some people just doesn't work because they don't metabolize it as well to the active form because their enzyme system and the way that it works and has about a 10 to 1 equivalency toe or or morphine. So say, if you're giving about 30 minutes grams of codeine. It's roughly the equivalent of about free milligrams of or morphine as an example. But that varies a lot, depending on how well someone metabolizes it, which is individual variability. Tramadol is another opiate, but it's it's a bit more of a dirty drug, Ailes, because that binds the other receptor that can also act as a neuropathic pain. A drug remember somatic pain caused by physical stuff and, in his neuropathic pain, nerve pain to very different types of pain. You know, if you do a pain medicine, I guess placement, you're you're you're learn a lot more about that, and that's also important. Part. Anesthesia is while morphine, but it's new opiate receptors. It's a direct, active drug. It can also be used in PC, A Space and Patient Control and Jeezy when it's when they used buttons, particularly in the context of general surgery on, they could get themself. Pain relief. Basically, oxycodone. It's a stronger version of morphine. Essentially, it can also be used in PC and fentanyl is the strongest in terms of the concentration are qualities and used fentanyl. An IV, which is typically used by nieces only specifically specifically during anesthesia, can also be used in PCs. It can also be used for other things, such as patients, that I see these firing off another example. Fine. So let's want to next question you're a 50 a medical student attending an elective gynie list. A 25 year old ladies on the Golden, an elective exploratory laparotomy for suspected endometriosis after induction. The Unisys and ministers on dansetron on dexamethasone, which receptor on the answer from work on Brilliant. Let's have been little looks at a majority of you. Answered correctly. It is the five ht three receptor. So what is one that's from So it's a serotonin receptor antagonists used Call me for my first line anti emetic. For the most part least, the Exelon, the vomiting center and the GI Guys inputs both internal vomiting, have sent it to prevent new Z and sickness, and the most important side effects to remember are prolonged QT, which is what you're looking at. You see GI on as well. Is that constipation, Um, and dexamethasone that's often used with it as an anti emetic to prevent sort of post operative nausea because specifically in sort of gynecological surgery, a lot of the issues post operatively. A postoperative knows it just because the nature of the bits that are operated on postoperative nausea tends to be a big issue, which is why they sort of pretty sort of anesthetic lee or drooling the anesthetic or just before the end of it. They administer on the answer from the dexamethasone together dexamethasone. We don't quite know how it gives. Um, it's anti emetic effects, but it kind of is sin. It's a synergistic with ondansetron and Hans effects on the five ht for your receptor. We don't quite know why, which is why it's given together, and it's sort of informally called dexa Tron D two receptors or dopamine specific di to subtype dopamine receptors. Metoclopramide is a type of anti emetic, which is a dopaminergic antagonised attacks on that and that can, and that's how it causes, sort of to be. That's how accident anti emetic and it tends to my second line issues with metoclopramide are is because it acts on dopamine receptors and it stops him from working. It can make parkinsonism waas. Or it can cause these sort of extra pyramid of symptoms and people that are prone to Tums. Um, s so that's we have to be sort of careful with metoclopramide, and the other thing about it is, it's also prokinetic. So can sometimes be used to help people constipated. That can help to be used to run the bowel along. But that's why it has to be careful when somebody's got bowel obstruction because those times that you don't want to be stimulating the bowel because it increases the risk of perfect as the bars trying to push against the block. Hi, that sort of makes sense. So that's when you need to be careful with multiple metoclopramide, in particular parkinsonism and bowel obstruction or anybody that's got sort of, you know, something bad going on abdominally that you're not quite sure about. Cyclizine is a fantastic antimatter, the actual histamine receptors, but because it acts on histamine receptors, has a sedating effect that patients quite like which makes it quite addictive to some patients that they get quite high offer That I remember is cyclizine histamine i n e i n e is the way that it ends on cyclizine in terms of side effects can also possibly more rarely. Prom. The prompt prompted Q t course sedation, as I mentioned, and it can also cause the quite strong tachycardia as well. Something's come raise the heart rate quite high up initially, especially intravenous cyclizine. So a little bit about sort of the vomiting centers and input in terms of physiology. So you got the vomiting center in your brain stem in terms of inputs, which always makes sense. Is things sensory input such as Fort smell seeing? You know, if you see your smell or think of something you don't like that can make you feel nauseous or six, Which makes sense. You've got your first stimulus system, which is, you know, moved in balance. So you know, things like car sickness, motion sickness, uh, you know, very to go when you get that sort of sickness. That's it's input into the vomiting center, and it's hate one receptors that are specifically there, which is why The only thing only anti emetic that really works for motion sickness or vestibular sickness or vertigo is psychic. See? So that's the antiemetics should be opting for rather than on dansetron a medical Promide. Otherwise, lance traumatic a while generally tend to work off all other things. You know, you've got some detail. Stuff is in the chemo trigger zone, so Metoclopramide tends to act there. So it's good for, you know, chemotherapy, opiates, anesthetics and so is undaunted from his well, where it acts on G. I am So. Chemotherapy, for instance, causes high turnover of got cells, which is why it causes diarrhea quiet and all those other side effects as well. That's why I'm on steroids, a good anti emetic for chemotherapy, because it acts in a G I input into the vomiting center. Fine. So that's just summarizing what I've told you already. Um, on as I said dexamethasone, you said just ically on Monster, but specifically only really an anesthesia, especially I be dexamethasone because it will cause sort of this perennial flushing. That's uncomfortable, but obviously, most of you will have come across that same episode in the context of Cove. It in patients requiring oxygen on that have covered. We give extra methadone because, you know, it's been shown to reduce mortality rates and help improve recovery in patients with over to that see other place and also has some anti emetic effects in that sense as well. So giving them on down strong on somebody that's with dexamethasone might be might be best thinking covered patients because it has that synergistic effect. So that's something else to think about. Side anesthetic room, Fine s. So we've got two more questions left. So urine f two and I see you. A 56 year old lady was admitted for vasopressin support following a nightly Austin information shoe to a sequel Perforation. Seven Days postoperatively. She becomes very delirious and believes the staff are trying to harm er. She's attempted to get out of bed and put out lines You tried to this the escalate, but you are only unable to What medication will you administer under the circumstances? Come back to the Suxenda phony, um, emergency setting question towards the end. So let's see the majority. You answered diazepam, which is the incorrect answer, but we're doing is based on UK guidance, I'll explain wide as prime is is, is probably not the right thing to do in this moment of time and explain why. So the terms of UK guidance, the first thing that you want to use is typically is lorazepam, So lorazepam is much more shorter acting in. There's a band that as a plan because of the way it gets metabolized and it's metabolite it can. It can be in the system for up to three days s. So that's a very long time. Which is why sometimes it's the choice of drug for, you know, patients there are about to go on undergoing MRI because you know it lasts for quite a while. But you really want to use lorazepam because it's shorter acting on. It's a benzodiazepine. As I mentioned, it's the dates because acts in the GABA acceptance and I could help calm the patient down, especially because they've got lots of lines they've got, you know, probably suture is, or staples or whatever. It's from the general surgery that risk of hurting themselves and others. So in this case, because the delirious and they probably don't have capacity in the moment of time, because of the delirium, you would probably give him a deprivation of Liberty Service, which is when you're sort of taking a patients rights away in a sense, and you would opt for lorazepam as a sort of rapid tranquil is a shin agent. First is what I'd say as a mentioned last time was a little half life a Lancet. Mean is one of the ones that can be used bookstore one receptors and can be used for rapid transit. But it's typically second line and typically better in the context of someone who's a bit more psychotic as well. And Propanols, uh, vita blocker that commute and anxious agents. We excessively a genetic symptoms, but it's it's no problem for the current situation, and it won't really help sort of calm them down. Really, it's just going to slow the heart rate on sort of the synthetic symptoms, Really. So, as I've mentioned, lorazepam can use for sedation, it's also and see let IQ commuting seizures are gonna force for poisoning, but also used in Iraq tracking protocol in the UK as a first line that as a partner is another sort of benzodiazepine, but again it acts for a much longer period of time. And a lancet means atypical antipsychotic, which acts a multiple receptors. And it's typically used second line and can be used sometimes in combination with antipsychotics. Last question. And then we're done. So your left one following a patient to recovery. A 45 year lady is just postoperative s o. Sorry, Just postoperative for Gyny said. You're not seven days, just postoperative. She's complaining of pain. Despite a fentanyl injection and having had intravenous proceed, tomorrow's well, the nieces administered intravenously. Paracoccidioides. How does it work? Okay, Britt. So let's have a little, uh so every he's answered. Or, for most part, are almost everything correctly. Correct interests. Cox two inhibitor. It's a selective cox two receptor inhibitor, so Paracoccidioides kind of like an answer that specific for Cox. Two inhibitor in and it's intravenous, and it reduces again Information pain. We'll talk a little bit about sort of the sort of head would look a little bit about sort of the physiology of all this. So as I mentioned new opiate receptors on binding sites of opiates in and orphans Cox, one inhibition is more related. Salicylates more related platelet aggregation and specifically primary hemostasis where you're forming that played a plug initially instead of secondary hemostasis, where you have sort of the fibrosure mesh forming and making a stable clot on phospholipase 80 inhibition is where steroids acting. We'll talk a little bit about sort of theory, academic acid pathway. And so the reason why I like the air in a record on a castle park for is one of my favorite part is because so many drugs are implicated in it took a little while. So the top of the chain you've got phospholipids and you've got four. So, like there's a two, which converts force for lipids into a racket Danek asset. Now steroids inhibit that, which is why steroids are useful in sort of ask, which will come down. They're sort of the right branches, which is why therapies for asthma but also used sometimes pain relief for reducing inflammation. But they also increased bleeding risk on also you increased risk, stomach ulcers and whole lot of others. That's gonna have so many side effects from steroids that we learned because it's on the top of this are academic acid pathway and affecting both of these projects, racism leukotriene specifically raise it, sort of implicated in asthma. And, you know, other bronchoconstricted diseases I mentioned on the prostate gland. Huge, too, which implicates Cox one and cox two sort of pathways. So when we go down the reconnect past a racket Danek acid pathway when it gets converted to cross the landing, hate to Can you go down the cox one receptor it a cox two receptor route Cox one is implicated in sort of, as I said with aspirin. So we're talking about sort of form from boxing on. We're talking about prostate prostacyclin. So from boxing, as I mentioned, is implicated in primary hemostasis player education. Vasoconstriction is what platelets read to help a plane aggregation on. Does a few other roles as well and Sinus say it's inhibit that, which is why you get less production of this and it irreversibly a city. LEIGHTS Cox. One wouldn't Cox two is what you need to know for your exams, and because it does that you increased bleeding risk. But it also acts on Cox two receptors, which are sort of, you know, implicated sort of inflammation and pain, which is why aspirin is sometimes used for pain relief as well for people who take it for pain relief as well. But it's not, as we don't typically use it for pain relief. But it's also implicating process cycling, which is through a gastric because of protection, which is why they increased risk of stomach ulcers and said's again also sort of act on cox one and cox two years I've mentioned. So that's why they help reduce pain and inflammation. But they also act on sort of renal arterial. So that's why you need to be careful with pre renal AKI zap on it. Also, you know, accent prostacyclin inhibits information of that, which is why you get increased risk of gastric bleeds on Do also just general bleeding. This is well because it's inhibiting sort of cox one and well. And then when we looked on the leukotriene pathway, we sometimes get asthmatic patients things like montelukast, which are leukotriene inhibitors, which sort of prevent the formation of leukotrienes, which cause broken constrictions. That house of bronchodilatation. And that's why steroids or so useful because again, steroids or just earlier pathway of this, which is why it's used in asthma s. So that's why I think if there's any coughing that you need to learn or should be, the record on a par acid pathway. And if there's any family of bacteria that she learned about should across Syria, the Clostridium family. So uh, that's it for this lecture we finished just about on time, actually, which is very rare for me. I think I'm getting better at this. Guys, thanks a lot for joining the first lecture of the Siris will have many lectures coming from which will also be taught by other S H O Z and sort of experience doctors in their own fields. Eso please join us for those, please make sure to fill out the feedback form. You know, all the teaching is free that we provide and the only thing that we ask already is is feedback for me, please. And if you want to get the slides and access to the videos, make sure you sign up to meddle, which is how we receive our feedback. And it's how you can get access to the slides when we release them, as well as the video content which will be released the next the following day after the Electric. I hope you all enjoyed it. I hope it was useful. Do you have any questions? Stunned into silence? I guess. So. It must have been Okay, then. So I just want to come back. Thank you, Patrick. So I just want to come back to, um a question about sucks and finding out why it's not used outside emergency setting. The simplest answer is it's because it's it's such has such an RC side effect profile as imagine. So in course, hyperkalemia. It's associate. It sucks apnea apnea. I have patients have called industries deficiencies. It can, you know, cause hypercalcemia. It's It's not as nice or is cleaner drug as the none depolarizing muscle relaxants are, so it helps. The reason I sucks is so useful is because one is it acts so quickly and two because of the visible fasciculation. If you're imagining urine emergency situation, the last thing I want to worry about when giving, say, a nun depolarizing muscle agent like like say, after a period, whatever it is is is you have the time for you have to sort of they they work within a certain amount of time, so you have to set them out of many or a timer for when you think the patient is paralyzed. While since sucks, you convince sublease E when they're paralyzed, which is why, in emergency setting, it means there's less to think about, which is why it's often used in emergencies settings. But because it's a dirty drug, you don't really want to use it any other circumstance, which is why they're, you know, even in our size or the emergency setting there, opting more towards rocuronium in higher doses typically. But it depends because anesthetic is a fantastic spectra. The anesthesia is a fantastic specialty, but it's kind of like sort of chefs. Different Chefs have lots of different ways for making the same thing. If that makes sense or anything, have their own sort of cookbooks or recipes or things they opt to choose to do so. Some people still optic choose you sucks. Other illnesses were up towards using rocuronium. It depends on what you're comfortable with, But Rocuronium sort of sucks in flames. You still only be used in the arse I setting or the emergency setting, where patient typically hasn't been starved. I hope that answers that question brilliant um, anybody else got any other questions? Apart from that? Anything else? Um, apart from that, always will probably ended there. And yeah, just just make sure. Please. Fifties. Fill out the feedback. Follow our socials. You know, our instagram or Twitter having to get the latest information about everything that's going on on. Please. Also, you know, spread spread the word about six PM Serious, please. It's all free teaching. Please spread it to your friends. It went against many people watching a Z. We can, because the more people will get watching, the more sponsorship we can get on sort of them or experienced provoked webinar providers. We can get for you guys as well. Again. All free on hope. You guys have a great evening. I think I just remembered Is a bonfire night as well. Ramone. Remember 15 November eso We're all a bunch of nerds, Kenny, because we stayed in tow. Watch this, but hopefully So you're gonna go out which the fireworks, and without further ado, I would say Have a great evening on, Take care of yourselves and see you soon on Monday, where the next lecture will be on the following part. One by doctor in Mary. Okay. Take care, guys.