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It should be fine. Ok, great. That's great. Well, we'll give everyone a couple more minutes. Yeah, guys, if you can fill out that feedback form, that would be absolutely great. It will, it literally takes three minutes and it will give you access to some really nice um Note banks on ay and also just on general conditions um to 1st, 2nd and 3rd years, the Note Bank is just give it one more minute for people just to get a coffee. It did. Ok. Well, let's get started on our next lecture which will be all to do with respiratory pharmacology and this will be given by Taika. So I'll let her introduce herself um in a minute. But guys, just a reminder, fill out um the few type forms if you can um both the post session and the ones uh separate to each session um to the question that just came in. Yes, it will come to your email. Yeah. And so when the Note Bank has been uh pub uh published, then all of those notes, you'll get a notification saying that it's published and you'll get the access to the notes. Um but let's begin guys, reminder if you have any questions, just put them in the chat um, throughout the lecture at any point. And I'll pass over now. Right. Thank you so much, Anita. So I'm Taa, one of the third year medical students at Queens University, Belfast. And today I'll be talking about, um, all the medications that are used to treat asthma and co PDI know when I was in first year learning this, I was so hard to get my head around it because there were so many drugs and so inhalers and they all had very similar mechanisms of action. So hopefully, um it'll clarify as we go along the presentation. And I've been co and I'm covering a lot of drugs um mainly short and long acting bronchodilators, methylxanthines, corticosteroids, leukotriene antagonists, mast cell stabilizers. And then we'll have some questions throughout. Um And as with all of these drugs, we'll be covering the mechanism of action in detail, the side effect profile. And when are these drugs sort of in what conditions are they contraindicated or need to be used cautiously? Um All right. So as with anything, let's start off with the very start. And I think it's very important to um have a good understanding of the anatomy and just how these drug work in a um physiological sense. Um and what the mechanism is. So the airway has smooth muscle, which is the primary, um which is the way uh most that these drugs do work. So they act on smooth muscles, especially the bronchodilators. And um the smooth muscle is present in the Bron bronchi and the bronchioles. Um And if, and I'll cover also the asthma and co PD pathophysiology just before we get into the drugs really briefly. Um And all the, both of them have to really do with the bronchi and the bronchioles and not so much the actual alveoli. Um So that's where most of these bronchodilators will act. Um So your airway has three sort of main innervation. And I think parasympathetic and sympathetic are the main ones. I wouldn't really be too focused on the third one. So the sympathetic innervation uh really the job is um I always like to think about is fight or flight and what can make um our body easier to fight or, you know, run away. So, um sympathetic system wants to dilate the airways. So whenever you're in that situation, it, it makes it easier to breathe. So if you associate sympathetic system with dilation, um of both the airways and the blood vessels and the main neurotransmitters that are responsible to do that is adrenaline and noradrenaline and they act on beta two and alpha one receptor. Now, I think to get a whole picture, it's also important to know that there are other sympathetic um receptors. So if you uh just re uh revise a bit of basic pharmacology, um you have a beta one which is majorly located in your heart. Beta two in the lungs. Beta three is more adipose tissue and then alpha one is your a um airways and also your blood vessels. Um the smooth muscle in your blood vessels and even beta two is in your smooth vessels. Um and alpha two is inhibitory. So it's mostly found in your nervous system. But this is very um simplified for today's purposes. All you really need to know is beta two and alpha one more. So, beta two is present in your lungs and then parasympathetic, you have um the major uh neurotransmitters is acetylcholine and it acts on uh muscarinic one and muscarinic three receptor and the oral effect is to constrict the airways. So I always like to think of those two systems a as um they're always uh uh they're always sort of um doing different things. So it constricts the airways and mucus secretion, right? So how does bronchoconstriction, bronchodilation works? And this takes us all the way back to when we learned about G proteins and what they do. And again, it's important to know this because um the dilators and the drugs we're gonna be talking about mimic uh physiolog uh normal physiology. So it's important to know how um they, these actions actually do happen. So, bronchoconstriction, like I said, is mediated by acetylcholine. Um and there are g, all of these receptors are G protein coupled, which means that they're attached to a G protein which then um which then stimulates further signaling pathways which ends up leading to the action, which happens bronchodilation or bronchoconstriction. So, acetylcholine binds to the receptors and they stimulate um either G uh GQ or GI. So GI stands for G inhibitory. So GQ um activates fossil uh lipase C which does a few things downstream. I don't know how much you need to know for your medical school, which then um activates um myosin like chain kinase. And that is one of the proteins that is involved in contraction um of smooth muscle. So, only smooth muscle, not cardiac or skeletal muscle, um and your smooth muscle, right? So it causes bronchoconstriction cause you're activating it. Now, G A and GSI like to sort of think of them as together. So what it inhibits the same pathway while one stimulates the same pathway. So, noradrenaline um binds to B2 and it stimulates that pathway and how it works. Is it inhibits at the end uh myosin uh myosin chain like kinase, um Myosin light chain Kase sorry um by increasing the levels of camp. So if you camp is one of those signaling molecules. Um So if you think of camp as if it's increased, it inhibits myosin chain like case uh light chain kinase hence causes bronchodilation and you'll kind of see where I'm getting um at this at the end because there are drugs that act in camp as well, right? So camp also has another mechanism. You know, it causes hyperpolarization. Again, you'll see why I'm talking about this because this is one of the significant reasons why you use salbutamol in the treatment of hyperkalemia, cause it causes potassium to go in. Um So all in all it inhibits CL MLC K um causes bronchial dilation. Now, um uh the other receptor for acetylcholine inhibits that whole thing. So you're inhibiting the inhibition of myosin light chain kinase and hence causing um bronchodilation, sorry bronchoconstriction, right. So, really, really briefly because I know uh there's a talk later on asthma and COPD as on pathophysiology. I like to think about it. I think of it as three things um that happens that leads to asthma. Um So there's obviously a trigger factor causing airway inflammation, then you have three things that happen afterwards and then it can, oh, it can be, there's a early response and a delayed response. So you get hypersecretion of mucus airway muscle constriction and then swelling or inflammation of bronchial membranes. And this causes all the symptoms and the narrowing and the um diural um uh symptoms and changes and shortness of breath, wheezing cough, tightness in chest and all the mediators that are sort of involved in this process are mass xenophilous xenophrys is very key to pa the pathophysiology t neocyte, which actually then attach to mast cells and then release cytokines and then which induces um maturation of the xenophilous um neutrophils and epithelial cells. So it, it is a very allergic type of reaction if, if I were to simplify it and then co PD pathophysiology has a mixed sort of pathophysiology. It's similar to asthma in the sense it causes mucus, um it causes mucus build up, it causes bronchoconstriction, however, it is more permanent. Um it's more permanent sort of inflammation compared to asthma, which is um um which is more sort of, it comes and goes intermittent and then you also have emphysema, which is this loss of elasticity and increased airway spaces. And that's why in an X ray, you sort of see flattened diaphragms and hyperinflation, right? So let's talk about anti asthmatic drugs. Now that we have a good overview, I like to think of antiasthmatic drugs as two tiered. So you there's cer certain drugs you can only use when you have acute episodic attacks. And then certain drugs you can only use as a preventative or um to reduce the frequency. So the ones that in acute setting or symptomatic relief or bronchodilators. So these are your short acting, not your long acting, your antimuscarinics and your Xanthine inhibitors. And then to reduce the frequency of attacks, you have your anti-inflammatory, you have your corticosteroids, you have your long acting, you have, you have your leucotriene um receptor antagonists and then you have your muscle stabilizer and anti I. So the last two are quite specialist. Um but I will just be covering it very briefly, right? So, um short acting and long acting beta two, a a an agonist. Um short acting, you have salbutamol and your t uh terbutaline, they have a very rapid onset action and a very short duration of action. Again, like I said, they're used for symptomatic relief um during an acute episode. Whereas your long acting, your sound terol and for uh Formoterol, they have a longer duration of acting and they're used um to prevent episode. Um And like I said again, they are agonists at the B2 receptor. So just to recap what they do is they stimulate that B2 receptor, they stimulate adenylate cyclase, increase the levels of cyclic P which causes inhibits um sorry, act inhibits M CK which causes um bronchodilation and then it also increases ciliary clearance inhibits me mediator release from the mast cells. So, in terms of adverse effects, um I like to think about um the adverse effects as sort of what will happen if I stimulate also the other receptors like your beta one, which is located in the heart and a lot of the adverse effects are stemmed from the activation of beta one and they particularly happen at higher doses. So, um so the common side, a adverse effects would be fine, tremor, headaches, muscle cramps, and muscle cramps would be to do with um the hypokalemia that happens. And if you go back to the diagram later on in your own time, you'll, you'll see that diagram again, it'll make it, um it'll make the concept a bit more clear. Um fine tremor really happens because you have your receptors that are also present in skeletal muscles, which actually um they get activated, which causes tremors. Um You also get tolerance with use um and then dose of dependent tachycardia and this is scan stimulation of those receptors in the heart. Um important are again, arrhythmias cause if you have hypokalemia, electrolyte disturbances. Yeah, myocardial um ischemia and in very, very high doses, you can get lactic acidosis. And um it should be used cautiously in people with diabetes because they can increase blood sugar levels and uh particularly at higher doses of prolonged use. And these are not complete contraindication. They're just in uh situations in people. You need to sort of have um um a awareness of all these adverse effects and hyperthyroidism. Again, because you know, hyperthyroidism is a disease that can affect your heart and cause very similar symptoms like tremors and tachycardia. So you wouldn't wanna uh you know, overdose them or give them a lot of um give them a lot. But again, they're not complete uh contraindication and then cardiovascular disease. So, moving on to muscarinic antagonist. Um so there again, they can be either short acting or long acting. Um So ipratropium, the duration of action is about 3 to 5 hours and tiotropium, the duration of action is by 24 hours and the way I like to remember because I always um mix up between the two is I comes before T so I short acting, T is long acting. So um these are Muscarinic antagonist. Um And you would think that they would have a lot of side effects, you know, antimuscarinic side effects. And I don't know if you've heard of the acronym Blind as a bad dry as a bone, um red as a beat. So what this, what all of these acronyms really are saying like blind as a about it causes m uh vic Vitis, which just means dilation of the people, dries a bone, lack of sweating, red as a beat, vasodilation, full of blasts, urinary retention and not as a hater of delirium. However, this is actually like these um the drugs are actually coronary derivatives of A B which is a muscarinic antagonist, but they don't really diffuse into the blood and they don't really enter the CN. So you have very minimal side effects and the only really common ones are dry mouth because you have um lack of secretion which is controlled by our parasympathetic system and oral candidiasis. Um The important ones to remember are acute Anglos glaucoma because as we all know, um it is caused by um uh one of the uh one of the sort of um well, I II guess I'll have to go to PA PA for that. But glaucoma is really like a muscarinic antagonist can worsen it just know that um and then urinary retention, like I said, and you just to be used in cautious when people with prostate um prostatic hyperplasia because um it can cause urinary retention and then um acute angle uh glaucoma, right. So, um let's move on to methylxanthines. And um this is sort of where um the, where it is and what camp can do comes into play because methylxanthines. Um So an example is amino FFI or fluy. So if you look at the diagram um at P is converted into camp by dilate cyclase. And as we uh as we looked before, this is the action beta antagonist and then C can get uh gets converted um into degradation products. And the, the enzyme that sort of um uh sort of does the conversion in the step is phosphodiesterase. So, methylxanthines are nothing but phosphodiesterase inhibitors and um they decrease um the sorry, they, because you're inhibiting the degradation, they increase the level of C which causes bronchodilation. Um And then you, there's some also other sort of mechanism of actions in that they block adenosine receptors. And then if you look at the diagram, adenosine um is a bronchoconstrictor. So by blocking it cause bronchodilation and then preventing diaphragmatic um fatigue. However, methylxanthines need be used with a lot of caution. They have loads and loads of systemic side effects, narrow therapeutic window and they have many, many, many drug interactions. So with that being said, let's talk, let's do a question together and I'll just open the poll. Um, right. So, um, I'll, and I'll just read it out. 23 year old female patient with a history of persistent asthma is currently prescribed theine for maintenance therapy. She presents to the emergency department with complaints of palpitations and nausea. And, uh, upon further inquiry, she mentions recent initiation of a new medication which of the following medications is most likely to have precipitated these symptoms by interacting with the afi salbutamol, Ium, carBAMazepine, Erythromycin and Phenytoin. So I'll give you just a few seconds for that. Right. I think I've only gotten one response so far and that was me so great. Got two responses. Three. Yeah. To be honest, this is quite a tricky one and it does involve the understanding of a few things to uh be able to answer this question. Ok. So I think I will stop the pill now. Um I don't know how to do that, but I'll move on. Um Right. So, um, the correct answer is Erythromycin, which I think only one of you got. Right. Um So, um, how do I work out this question? Right. So we know that she's been prescribed theophylline and she's been having adverse effects. Now, these adverse effects palpitations and nausea, you have to know, are they because the, the drug in your system is being um decreased or is it at a higher level? So, is it at a lower level or a higher level than the therapeutic index. So if I know my adverse effects for theophylline are you know, palpitations and gi upset. I know, OK, so this drug is actually increased in her system because of some interaction. Now, I also know um that theophylline is ac YP 450 inhibitor. Um sorry, uh not inhibitor, it is metabolized by CY P 450. So because I know those two things I need to find which of these drugs are inhibitors. Now, if II always like to think about is as inducers, they decrease levels because um inducers are sort of, they're, they're um inducing the enzyme. Hence, more of the drug is going to be metabolized and it's gonna uh lower down the, the drug levels where, whereas if I get an inhibitor, it's going to be increase levels. All right. So um I'm just gonna move on to the next slide and this is where I sort of explain um it a bit better and I always found it very tricky to under and uh what induces and what inhibits. But I have a really good Pneumonic and hopefully that'll help in the future because you do get a lot of questions um that are pure memorization based, but you with the Pneumonic, it should help. And so like I said, um methylxanthines has a very narrow therapeutic window. What do I mean by that? So if you look at this diagram over here, um, you see that, um, it has, um, uh, this is maximum and this is minimum concentration and you need to be within that therapeutic window and same over here. But because it's narrow, it's easy for the drug levels to fluctuate. Right. So, um, it's how it's metabolized. Um, but just before I'll talk about the side effects. So, if you didn't know methylxanthines is actually, um, found in caffeine as well. So, whenever I think about the side effects, I associate that with caffeine. So, um some of these um side effect are um you know, uh if you just think about it systemically, lungs, uh it causes bronchodilation, you know, we talked about this and then improves ventilation, cardiovascular, they're tachycardic, you know, um and then gastro, you know, they sort of increase gastric acid secretion, nausea and vomiting. In fact, if you think about Gord, um you're actually not allowed, they, they tell you to cut down on your caffeine and coffee and it is because of this reason. So whenever you think about this, just think about caffeine and what it does to you, right. So, um in C NS, it causes tremors, nervousness, insomnia, convulsion, right? So, C IP 450 inducers and inhibitors, there is a wide range, but the trick is, and I've, I've realized if I just remember my P 450 inducers and the mnemonic CRP G psi will be able to answer every single question. So, uh P 450 inducers are crap GPS. So, carBAMazepine rab uh rin alcohol, phenatoine. Um I'm not gonna pronounce that word phenobarbitone. And so no. Um So if I go back to the question, if I were to eliminate, I can easily eliminate salbutamol and II, because I know they don't induce or inhibit cause I've already also talked about all the side effects and have not mentioned that carBAMazepine, if I go back to my CRP GPS, it induces. So that's wrong. And P is also present in crop. Uh sorry for saying CRP so many times. Um and it also induces. So, Erythromycin is the only one that inhibits. Hence, that's my right answer. OK. And then I have this here to just revise um when you go back on the slides. So we're almost there. Um Cortico uh cords are probably one of the most important ones and they're sort of prescribed and you will see like blue, um blue colored inhalers, so not blue brown and then the salbutamol is blue. So um the mechanism of action is that it inhibits phospholipase A two. I know this is a lot of like um biochemistry um and pathways, but again, it's important to know. So you have your lipid membrane and then that converts into Archon acid and then that is sort of converted to prostaglandins, leukotrienes and some other things, other, other things we don't need to know. But this is actually a very, very important pathway and there's so many drugs that inhibit or alter this pathway. So, corticosteroids always come at the top. They, they stop um sort of um formation of uh inflammatory um s um signaling molecules. So your prostaglandins, your leukotrienes and then your other drugs come a bit below that. So we'll talk a bit about leukotriene inhibitors and it also acts on this pathway. Um And so they're anti-inflammatory. They also have uh effects that include mast cell stabilization, up regulation of B2 receptors. They're used for prophylactic therapy. And again, they're not bronchodilators, they're anti-inflammatory. Um So you oh you can have these drugs through um in three sort of ways um inha inhalation, orally or injection. Um And those are, which drugs do you use for? Whichever way of um uh way of usage? Right. So let's move on to the second question and I'll um start pulling. All right. So um question two, a 10 year old child with moderate persistent asthma has been using inhaled corticosteroids with a pacer for symptom control. Despite proper inhalation technique, the child presents with a bite, coating on their tongue, which of the following interventions is most appropriate to address this issue. So, a discontinue the uh I CS immediately and switch to leukotriene receptor antagonist. B, increase the frequency of oral hygiene measures and continue the current I CS therapy C switch to dry um powder inhaler for delivery of I CS medication. D prescribe an antifungal mouthwash and continue the current I CS therapy with a spacer and e refer the child to a pediatric allergist for further evaluation and management, including consideration of immunotherapy. Oh, I think I pulled the wrong one. Sorry about that. Um, oh, I think I don't have this question on my. Oh, I do, I do. Sorry. All right. Um, sorry for that. Just give me a few seconds there. Ok. Ok. Right. So I've gotten four responses so far. Um Just gonna wait for a couple of more, but all of you are doing really good so far. Right? Ok. So the correct answer is d um So this is oral candidiasis. Um And you can sort of see white plaques on the surface of the tongue. And how do you differentiate that with leukoplakia? So, um you differentiate that with um oral candidiasis if you swab it actually scrapes off. Whereas uh leukoplakia, it's a precancerous lesion. It does not. So, um, like I said, with inhaled corticosteroids and antimuscarinic, one of the side effects is the development of oral candidiasis specifically with I CS. Um And you get local sort of symptoms, you can get dry mouth, you can get um oral candidiasis and it is not really a big deal. It's just um for pediatric Children specifically, you do use a spacer and um you and then you can also prescribe antifungal cream. So the other options are quite strong, like there's, you don't need to change medications or change the delivery, I guess if it's very continuous, um you could change the delivery. But a lot of the times with antifungal mouthwash and using a spacer, you almost minimize completely the development of oral candidiasis. Right. So, um glucocorticoids continued. Um you have low, moderate and high dose and it is prescribed in different um steps of the asthma management um and um systemic corticosteroids. So the oral ones are a are only really used in the severe asthma cases. And you don't really see people prescribed on prednisoLONE for asthma. Um and adverse effects are like I said, oral candidiasis, you get dysphonia, you can get dry mouth. Um And then um if you're prescribed oral, um you know, there's a huge array of side effects. And again, I like to think about it in two ways. Um First, the systems and then the second also thinking about the mechanism of action and then thinking how it affects each of the systems. So M sk you know, your glucocorticoids are a cata uh catabolic. So it cause bone destruction, osteoporosis, um fat redistribution around your tummy, around the back of your neck. Uh ca ca called the buffalo hump and then around the cheeks. So that's called a moon face. Um and then wasting of muscles, um immune system you're prone to infection. It's an antiinflammatory drug. You're inhibiting all the white blood cells that are supposed to do their job and prevent infection. Skin is dry and bruising. One of the um uh thromboxane A two is a procoagulant, which is part of that pathway and it, it, you're not really producing that or not as much and really can cause bruising because of that. Um e endocrine hyperglycemia adrenal suppression cause you're suppressing your H VA access, fluid retention weight gain is because corticosteroids can act as mineralocorticosteroid, um which are basically aldosterone and those are what retain fluid. Um Psychiatry can cause uh psychiatry can think about psychosis and hypertension. And now one thing to be cautious about it more so with oral corticosteroids, not with inhaled. If it's greater than two weeks, it should be avoided. And those should be tapered to avoid adrenal insufficiency syndrome. And how are you prescribed inhaled steroids? They really should be considered for people with any of the following features if they or if they use a, their blue inhaler or salbutamol for more than three times per week if they're symptomatic three times a week or more. And if they're waking up at night, uh more than once in a week. So, um I just wanted to sort of cover um modes of delivery really briefly and the differences between nebulizers and inhalers because I knew I know I always got confused um between the two. So, uh nebulizers is really just a machine that sprays this liquid medicine. So, the same medicine um into a fine mist which you sort of wear this mask around your nose and mouth and you inhale it. Whereas inhalers can be of two types, they can be meter dose inhaler, which is what you see and a circular sort of dry powder which you inhale really quickly. Um When is it used, nebulizers are really for severe asthma. You know, if the patient is unable to take their inhaler for young Children, whereas inhalers are regular use, you know, they're for patients that are good. Their technique is good and can use them effectively advantages. Um nebulizers are, are again easy to use. You know, you just sit at a place you put it on your face. Um There's no really need for strong inhalation and they can also be supplemented with oxygen. So, in a hospital setting, you will see people with uh using a nebulizer set of their inhaler, especially if they're really weak and if their respiratory muscles are really weak because inhalers, they require very s uh uh they require strong inhalation. So, um but inhalers are all small and easy to carry, they're handled devices uh and they're quite quick. So it takes 10 seconds. Um and it can also be used with a spacer. So, leukotriene inhibitors, um this is one of the last few drugs that I'll be talking about. Um So uh you have your Montelukast, your Zir Lukas and your Prime Lukas, they all end with Lukas t um convenient um their mechanism of action there. So, again, if you go back to my earlier s slides, lipo Trys are produced by the action of five lipoxygenase on Arachidonic acid. I'll actually just go back really quickly. So you can see it. Um I think it was here. Yeah. So um Arachidonic acid converts into leukotrienes. So, leukotrienes are major bronchodilators and inflammatory cell um mediators. Um And then you have your lipo ox uh lipoxygenase um which converts that. So, um um so the, the drug that inhibits it is actually ZZZ zone um which inhibits that enzyme which converts to leukotrienes. But leukotrienes inhibitors act directly on the receptors. So there's many types of leukotrienes. Um The, the main one you really need to know is B four and then CDC four D four, E four B four causes chemotaxis of neutrophils or just a fancy way of saying neutrophils. Um it causes the neutrophils to accumulate or go to places of inflammation. Um And then the other ones causes bronchoconstriction, hyperreactivity, edema hypersecretion. So, as you, as you know, all of them are related to the pathophysiologic as, as uh sorry. So, um the overall effect is bronchodilation and have inflamma anti-inflammatory action and they're used as prophylaxis. Now, they are really good, but they are less effective than steroids. But if you use liquid trials and steroids together, you have an additive additive effect. So they are especially really good for aspirin induced asthma, which I found very interesting and their adverse effects sort of include hepatotoxicity, hypersensitive sensitivity reactions, headache and agranulocytosis. Right. So, mast cell stabilizers and um these are really niche drugs and the next two are also very niche. So I'm really gonna talk about them very briefly, right? And they stabilize the mast cell membrane, prevent Regan degranulation and acute asthma symptoms. So if you look at a mast cell just at the picture, um below, um they have receptors in which they sort of um uh you know, mediators mind too, like IG et cells and they have antigen receptors and then that's how they degranulate when they get the signal. But if you prevent the degranulation, the thought is none of the things would happen. Like they don't release histamine or um uh don't release histamine and other mediators. So, um they're indicated for asthma allergic rhinitis and other allergy related conditions, but they're very, they're very rarely used. I haven't really seen them in guidelines as much. And then the really niche ones are the monoclonal antibodies, you of your IgE and anti IL five. So, um I ge as we saw, um it will bind to the mast cells and it causes degranulation. So the idea is if you block or if you, you know, have a monoclonal antibody, which sort of just captures I ge um it's going to not do that. Um and not release all those um mediators Il five. Interestingly, if you know your pathophysiology really. Well, IL five is one of the interleukins that causes a xeno maturation um and differentiation. So, if you inhibit that, the idea is you don't really see um is in a film mediated um inflammatory reaction, which is the key sort of in asthma. And um again, these are very niche. I've never really seen them in guidelines, but it's good to know. So, question three, we're almost there and I think that's all the drugs covered. We'll just have a bit of guidelines now. So um question three, I'll just put up on the poll. Um One second. OK. Yeah, I think that's the one that was below before. The one. I, I don't know how to Yeah. Um I think I might have messed that one up but OK, it's fine. I'll just go through the question. Maybe you can just write it or put it up in the chart. Um Your answer. So just type this one. So the question is you, you a 60 year old woman in the CO PD clinic? She was diagnosed with CO PD four years ago, currently maintained on Salol inhalers required her latest FU B1 was 42% of predicted. Despite her current therapy, she has frequent aspirations. So um there's no history of asthma, a xenophila or FE B1 variation. So she's on a salbutamol inhibitor uh inhaler. Sorry. Um And this is sort of the status of her CO PD. What is the most appropriate next step in her management So a salter inhaler B in increased dose of salbutamol c combined salmeterol and fluticasone inhaler. So, um it's a steroid um combined sanol and two tropium. So that's a lama um and oral aminophyline. So just type your answers into the chat. Yeah, a couple of you guys are getting it right. So the answer is d um oh sorry. So in CO PD, um a person that is still breathless despite the use of a Saba or a Sama and they have no asthma features. So no steroid responsiveness features will include um you know, um they have no asthma, steroid responsiveness. So those features, you know, are, you know, if they have dizziness or xenophis or if they have sign of atopy um or asthmatic features, you add a Laba or a Lama um if there's no asthmatic features um and then let's just quickly go on the guidelines. Um So Saba or Sama is required, that's the first step. I always get that wrong cause I'm like, oh go, go straight to the long acting cause it's CO PD but no, start with Saba or Sama. And then if they have asthmatic features, if they don't have asthmatic features, then you add a Lama or a Laba. Um If, if, if it's no and then if it's yes, you add a laba um um and an I CS regularly. Sorry. It's a Laba and Alama. No or um and then if that doesn't work the third line is you kind of add all the medications together and hope for the best. So, question four, a 18 year old female comes to the GP for an annual asthma review. She reports a worsening of symptoms in the last few months requiring her blue inhaler almost three times a day. So it's quite bad. She currently only uses her blue inhaler. She's otherwise well and has no allergies and is on no other medications. So what is the most appropriate next step in her management? Add a low dose bidenoside inhaler, add a serol inhaler, add a tiotropium inhaler, add a oral Montelukast. Um It's a leukotriene inhibitor, um receptor antagonist and beclomethasone inhaler and E at a medium dose bidenoside inhaler. So I'll just get the pull up. Ok. So we're really getting a good range of answers here, I guess with asthma guidelines, they're always changing and they're gonna change again this year. So, um the people that are in clinical years, it's really annoying to know this. But I think even in preclinical, you might be tested on the first or second line of management. Uh I'm not too sure but it's, it's important to know at least the first two steps. Um because the third is where the two guidelines, the BT S sign and the nice guidelines differ. So only one of you got the right answer and not. Um And that was for me. So hopefully this the next step, the next slide will explain it better. Um So the correct answer is the first. So um both guidelines. OK. So before I go on explaining this, there are two guidelines for asthma. You have your nice guidelines and your signed guidelines in the picture above. I've only stated the nice guidelines. You're not really going to be tested on asthma guidelines in your exams just because there's so much diff differences. But um in 2024 in May, um they are updating the guidelines that are combining BT S sign and NAS. However, for the first two steps, both of the guidelines are the exact same. So if Sabba doesn't work, you go on an inhaled corticosteroid low dose, you always try that first before going to medium, before going to high. So um the key difference in the two of the guidelines as of right now is that in step three, instead of adding a leukotriene receptor antagonist, you add an sign uh sign guidelines say you add um a uh one sec, let me just read patients. Yeah, there, there um they add a laba or a long acting bronchodilator instead of LTR A. Um And then all the other steps are sort of somewhat different. So that is one of the biggest things, but the first two are the same you always have because if you think about it, she's having a lot of attacks, you want to prevent it. So you wanna give a steroid um instead of um the other drugs. So, and uh uh steroids are the most effective preventative. So you always give a steroid first. OK. Last question. And I think this is quite an important question because um we've talked about all these drugs, I think it's very important to know how to describe how to use these drugs to patients. And if the drugs are not working because of this and, you know, like it's very important to have a um idea of what the inhalation technique is. So I'll start pulling now. Um So a 23 year old man attends the routine asthma review. He takes his sal uh salbutamol saba for his asthma during acute attacks, but tells you that he's currently has had no effect from his inhaler upon the demonstration of this technique, you've realized the problem. So he's not using it correctly. What advice can you give him on his inhalation technique? A after inhaling a dose of the medication, he should ideally hold his breath for 10 seconds. B after inhaling a dose of the medication, he should ideally hold his breath for five seconds. C after exhaling residual air from the lungs, hold for 10 seconds and then press down the canister. D after exhaling the residual air, hold for five seconds and then press down the canister. Um E press down the canister for 10 seconds while inhaling and exhaling for 10 seconds. Good. Um A lot of people are choosing the right answer. So the correct answer is a, um, you have to hold the, whenever. So you're shaking the inhaler, put it in your mouth. Um, when you press on it, you have to, um, take, you have to hold it for 10 seconds for all the medic medication to go in your airways. So, let's talk about the inhalation technique really briefly. So, and, you know, this is a ay station like, um, I'm a third year student. So we, we get a lot of clinical um scenarios in our acies and um you might get this even in preclinical years. Um And uh uh the demonstration of how to do this is very important and also how to explain it to a patient. So remove the cap and shake, breathe out, gently, put it in your mouthpiece. Um And then, so before you even put it in your mouthpiece, you have to breathe out. Um and then you have to seal it. So you have to seal it properly. And then when you press it, you uh it should be, your breath should be slow and deep and you have to hold for 10 seconds um or as long as it's comfortable and then if you, and then that's it. So if you wanna take a second dose, you have to wait 30 seconds before doing um repeating steps, 1 to 4. OK. So that is um it um I just have a brief summary slide. It has sort of all the medications and where they inhibit. Um, and I have covered almost all, um, of the medications and the drugs you use for asthma and COPD in the guidelines as well. So, hopefully that is helpful. Um, and if you do have any questions, please let me know and, um, Anisha will give a feedback form. So I'll be really grateful if you can fill that out. It, it just helps me improve my future talks. Um, and if there's any questions you can email me or ask now and hopefully I should be able to answer. Thank you. Hi. Thank you so much for that talk. Tolia. That was amazing. I wanna see a really, really good summary of the medications. Um, guys just, just to clarify that you will be getting the slides after and you'll also have access to the lecture recording. So you'll be able to watch back on all of the, um, talks which have happened today that will be through meal, but just a reminder, the feedback form which comes at the end um, of all of the lectures today. If you fill that out, then you will have access um to, um, all of the slides and lecture recordings. So make sure you fill that out. Um, but, uh, does anyone have any questions for Taika? No, you, well, um, if not, then what we can do is we can take another five minute break. Um, get a cup of coffee, you know, stretch your legs. And then we've got um actually only one last presenter today. So our last presenter today will be Rohan Patel who will be um presenting on ABG S. Now. Unfortunately, the last presenter today who was presenting on respiratory diseases, he can no longer make it. However, he's prerecorded his um lecture and it will be on medal for all of you by the end of tonight. Ok. So you can watch that and that will be covering all of the respiratory conditions looking at the summaries to do with them and uh such as COPD asthma, uh respiratory failure and um pulmonary hypertension, pulmonary infusions, pleural effusions and um pneumothorax. So that will all be available for you to watch and the slides on that as well. So take a, take a break guys and Rohan, if I can just ask if you could come on to stage and we can set you up if possible. Hi guys. So you actually have a little bit of a longer break. So we'll give you until about 1145. So yeah, take this opportunity just to stretch your legs, but we've already got one more talk left for today. Please do um you know, keep uh interacting. This one is probably going to be one of the most useful ones for your exam. As a lot of your exam questions will be on A V GS and interpreting them and it can be a place that a lot of students do struggle with. So um take a five minute rest and then we'll get cracking. Hi Rohan. Yeah. Hello. Ok. Do you wanna try sharing your slides? Yes. Well, try and how's it been today? Yeah, good. The talks have been excellent. So far. So tough act to follow. Um, yeah, and rest. Um I'll probably log on to monitor the chat on another device. Yeah. No worries. That sounds good. You can see the, the screen. Yes, we can see your slides. So um yeah, we can just let me know when you're ready and we can start to be honest. Yeah, I'm on another device. Yeah, that. Ok. Exactly. Yeah, I to me. Ok. Ok. Um and I'm just logging on. Mhm. Yeah. Ok. So. Ok. Yeah, I think I've got it up. Um So yeah, whenever ready, whenever amazing. Well, I'll just quickly introduce you. So guys, this is our last talk of today reminder that the other one will be put up on medal for you all to watch in your own time with the lecture slides and the video recording. But right now we're gonna have a, an amazing talk on ABG S and interpretation of ABG S as well by Rohan Patel. And I'll hand over now for uh to introduce yourself just a little bit more. Ok. Hi everyone. Um Thanks for the, the welcome in. So I'm delighted to give a talk today on Arterial Pocas is A B and GS. Um And I am also part of the uh be a committee. I'm one of the preclinical education officers. Um so who has helped organize um some of these talks. So I hope you find this talk useful. If you do have any questions at any point, please do feel free to put it into the chat. So without further ado, so just to introduce who I am, sir, uh my name is Ron Patel. I'm a third year medical student at UCL currently in in cardiovascular science at UCL. And my, my dissertation at Barts NHS Trust is focused on investigating the association between deprivation scores and cardiac implantable electronic device arrhythmias. I have uh an interest in medical education and I'm also the Preclinical Education Secretary for UCL Medical School's cricket club as well as uh being both a senior and transition mental first year student at UCL medical school. So let's go into the topic. So this uh tutorial is gonna focus on ABG S arterial blood gasses. We're gonna break it up into three sections. So an introduction, an interpretation guide and case studies. And really this tutorial is focused on preparing you for exam questions. It's a very common common theme in exam papers. They'll give you a ABG and they'll ask you to interpret it and ask you what's happening. OK, so let's introduce the topic. So to start off with. OK. Uh what is an arterial blood gas. Well, an ABG is a blood test that is used to give an indication of ventilation, gas exchange and acid base status. Most important one we're going to focus on today is the acid base status. Um, and it's taken from, as in the name from an arterial blood supply. Ok. So, um, it's one of the most common performed procedures in intensive care units and I've put on the right hand side, just a picture of an ABG. So once you take the blood out of an artery, OK, you'll send it off to the lab and this is what you'll get back. OK? And we're gonna focus on some of these different ones today. You'll usually be given the uh the normal range. So don't worry about learning, learning that. So let's go on to the next part. So interpretation guide. OK. So it's gonna talk a little bit about how to interpret ABG. OK. First thing you want to do is to look at the PH, to find out if the patient is acidotic or alkalotic. OK. That's the first thing you want to do. Um And you, if the patient's PH is less than seven, as you know, it will be a acidotic. If it's greater than seven, it will be alkalotic. Now, the second thing you wanna do is you want to look at the P AC two, OK. The partial pressure of carbon dioxide in the artery, OK. And the P ACL two will tell you whether it, there is a respiratory issue. So if the PC two is high, there's lots of carbon di carbon dioxide. Ok? And carbon dioxide is acidic, there will be a respiratory, it will be respiratory acidosis. However, if it is low, that means there is a respiratory alkalosis. Ok? And hopefully this should account for the PH. But if you come across that the P AO two does not account for the change. That means there is a metabolic problem. So what you wanna do is you want to look at the HC 03, the bicarbonate. If the bicarbonate is low, there's a metabolic acidosis. OK? If the HC three minus the bicarbonate is high, there is a metabolic alkalosis. OK? So a good way to remember is that lots of CO2 means there's um there's an acidic environment and lots of bicarbonate means there's an alkalotic environment. Um And then that of fusing all that you wanna match out. But we'll talk more about that later on in the talk how to do it um with an ABG. OK. So these are the normal values as we looked at. OK? You'll be given these. So don't worry too much about those. I, I'll put, we're gonna look at a few case studies and I put the um the normal values in there. All right. So, so the first thing we're gonna talk about is metabolic acidosis. There's an excess of acid in arterial blood. Ok. Metabolic acidosis will usually be due to having a low bicarbonate. Ok. There's many different reasons for this and usually in exam questions they will ask you can if let's say there is a metabolic acids and they'll say no, give me one reason for a one po potential cause and then these are just some of them that you would need to know. So for example, you have too much acid ingested and aspirin overdose too much acid produced. It could be during cardiac arrest. Ok. Uh Too little acid excreted eg and renal failure, too little base produced eg and renal failure or too much base excret. That could be um something to do with the gi tract or renal tubular acidosis. Ok? And I have also put out that this could be due to respiratory alkalosis in compensation. So we will talk about compensation in a bit more detail afterwards. So next one is metabolic alkalosis. So we talked about acidosis. This is alkalosis. This is where you've got an excess of base or bicarbonate in the arterial blood. Many different reasons for this is there could be too much base ingested et antacid, too much base produced. Usually um it could be due to compensation to respiratory acidosis or too much basic sweet excess vomiting. Ok. And another reason could be K plus deletion or burns. I think the most important one would probably be the first one. Too much based ingested antacids. Definitely have an example for metabolic alkalosis. Ok. Next one is respiratory alkalosis. So this is when there is a low uh partial pressure of CO2 in the arterial blood and this is usually caused by hyperventilation. So when you hear about hyperventilation, you want to be thinking about respiratory alkalosis. Ok, breathing out your hyperventilating, your breathing very quickly and you're breathing out all that C two. So you've got less in your arterial blood. This could be due to certain drugs, aspirin or doxapram. Uh it could be compensatory to metabolic acidosis. It could be due to anxiety. So if you, if you hear about anxiety, you might also hear about hyperventilation and that could be lead to respiratory alkalosis. It can be due to type one respiratory failure. Ok? And those living at high altitude to be breathing more heavily to get more oxygen. Ok. Right. So that's respiratory alkalosis. The next one final one is respiratory acidosis. Ok. And this will be due to a high p partial pressure of carbon dioxide in the arterial blood. Ok. So again, this is like what we said with respiratory alkalosis, it's due to hyper ventilation, breathing very heavily. Respiratory acidosis is due to hypoventilation. And this is most notably caused by certain drugs such as opiates or barbiturates. Ok. So if you do, you probably have heard about patients with an opioid overdose, they are hypoventilating and this can lead to respiratory acidosis. Ok. Too much CO2 and arterial blood, it could also be compensatory to metabolic alkalosis. Ok. Uh The second reason could be an inability to clear CO2. So you're retaining all that carbon dioxide. Ok. And it could be due to uh pathology in the lung uh in the parenchyma. So COPD or in the airways that say an obstruction, other thing is also respiratory muscle fatigue or weakness that can lead to CO2 retention. All right. So the next thing to talk about is compensation. So what is important to remember is that the body is gonna try and return the ph to the normal values throughout compensation. So for example, let's take metabolic acidosis and metabolic acidosis means that HC 03 by the bicarbonate is low. But what we wanna do is we can, we can the body will compensate that by lowering the P CO2. So that ratio is constant. Again, the body will lower the P CO2 by hyperventilating. And this is known as compensation. Two terms to be aware of. Now, partial compensation is where compensation is occurring. So let's say there's a metabolic issue or you look at, you look at the respiratory component if compensation is compensation is occurring, but the PH has not returned to normal values, then it's said to be partial compensation, complete compensation. OK. Uh means that compensation is occurring and the ph is returned within normal limits. OK? And we'll look at a few, look at this in one of our examples. So let's look at metabolic acidosis with partial compensation. So, if it's metabolic acidosis, OK. The PH is gonna be uh low, which it is low. OK? And if it's metabolic acidosis, therefore, it's something to do with the bicarbonate, right? And if the bicarbonate, yeah, is very low, that's what's going to be a metabolic acidosis, right? And what has also happened is the PC two has gone down as well. So that is because of compensation and that is how you would work that out. I hope that makes sense. So this is metabolic acidosis with partial compensation, right? So uh let's go on to the next part, which is the case studies. OK. So if you've got any um questions, please do, let me know just take a minute if in case anyone's got any questions, otherwise we'll move on to the case studies. Yeah. And if you can't hear me, you just let me know in the chart. So let's look at the case studies then. So I've got a couple of case studies for you. OK? This is the main part. It's the most important part of uh the talk. OK? This is what you're gonna be getting. I've put a couple of case studies and this is what you'll get in your exam. So let's talk, let's look at the case one. This is Missus D. OK? So MD is a 22 year old and moderately dehydrated woman. OK? 22 year old, moderately dehydrated woman was admitted with a two day history of acute severe diarrhea. Ok. Her ABG is as follows. Ok. So ph of 7.31 P CO2 of 4.4 po two of 10 ht 03 minus of 16. So give you one minute to have a think about that. And what I want you to tell me, I want give me what you think is going wrong here to tell me whether it is a respiratory problem or metabolic problem. That would be the first mark you'd get and whether it's an alkalotic or acidosis and whether there's any compensation coming. So spend a minute and then if you put your arms in the chat, please. OK? You got one on same good. All right, good. Anyone else? Yeah. So yeah, you're all correct. So it is metabolic acidosis. OK? Um The reason why just to go through it. So it's, it's gonna be acidosis because the PH is low. OK? Um 7.31. Then we look at the PC two C three. Well, the PC two, OK. Some of you, someone did say that it could be respiratory compensation, potentially it could be, I think it's very, very close to the threshold. So 4.5. So I probably say it wouldn't be respiratory compensation but it's on the verge of it being respiratory compensation. Ih three as the biggest one right is 60. It's very low and that would be the reason why it would be metabolic acidosis. And the po two, they just put it in, but it's not really significant. And it said another thing, an important um uh giveaway is that this patient has acute severe diarrhea. So if we just go back to what we said about metabolic acidosis, OK. Um is that this could also be a giveaway. So if there's, let's say um this because this patient has got diarrhea and this could also be another giveaway. OK. So let's now move on to the second case study if that's all. OK. So this is Mr G. OK. I just read through it. So a 75 year old gentleman living in the community is being assessed for home oxygen. His ABG as follows ph of 7.36 PC 27.6 po two of eight ho three minus 31 base excess of plus five. OK. And now the values are within normal range. So just tell me what you think could be the possible diagnosis. Put you in the, in the chat when you're ready. Yeah. OK. So it's a question about uh let's see. OK. There's a question about what is base access. OK. Well, the base excess, OK. It's an indication of the metabolic component of acid base status. So if you've got a high base excess, OK. That means there's lots of base and the base in this case is the bicarbonate. OK? If you've got lots of base that's gonna be indicative of um a metabolic acidosis of alkalosis. Sorry, if you've got a low base excess, let's say it's minus, let's say it was minus uh five, for example. So it's, there's a negative base excess that means it's a metabolic, there's metabolic acidosis. Ok. So the base excess just, it just summarizes what the bicarbonate is uh saying, OK. And it's more easier in easier way. Does that make sense? It's a metabolic alkalosis again, a few more answers in, see a minute. So what I'd say is so first of all, think about uh look at the PA it's 7.36. OK. Yeah, good answers in. So 7.36 right? That's on the verge. It's in within the threshold now, but it's on the, on the verge of the low, on the low side. OK. So there's gonna be something that's an acidosis going on. OK. Then you want to compare that with the PC two and HC three, the PC two is very high. OK. And that is indicative of an acidosis. OK. A high bicarbonate does not mean there's gonna be acidosis there being alkalosis. So therefore, it's gonna be respiratory acidosis with um with uh compensation. OK? There's gonna be compensated, respiratory acidosis and you, as some of you said, it's respiratory acidosis with renal compensation. So that's really good. Yeah. Really good. So I hope that makes sense like a tricky one but the first thing to do, as we said in the guide, I've got the guide here, I'll send you all these slides afterwards. Ok. First thing to do is to look at the PH OK. Is the patient acidotic alkalotic then go to the PACO two. Does that tell you anything? And then go to the bicarbonate? Ok. And just remember that high CO2 lots of CT will mean um, an acidotic patient. OK. And a low um a a high bicarbonate. So bicarbonate is alkaline will mean there's an alkalosis, that's the way I'd remember it. OK. So just going back, we've done case two. Yeah, hopefully base excess makes sense to you if you come across that. So base excess just modifies what the bicarbonate is. Saying a high base excess means there's high bicarbonate, a low base excess means there's low bicarbonate. So let's go on to the next case. Case three. Mh OK. So using the previous two cases, hopefully that's helped. You must have gone on to the third case. So 22 year old woman presents feeling acutely lightheaded and short of breath. She has a final university exams next week. Her ABG is as follows PH of 7.48 A P CO2 of 3.5 po two of 12.1 bicarbonate of 22. A base excess of plus two. So have a think about this one. Everyone spend two minutes on that before we go through it, these are the sort of questions you'll get good. OK. Any one else. Yeah, so good. Hold on. So yeah, this, this is an example of respiratory alkalosis. So the PH is um high 7.48 the PC two is is low. So therefore it's going to be a respiratory problem and a low CO2 will mean that there is gonna be um a high Ph, OK. The bicarbonate is not really significant, the base is not really significant. There's not really any compensation going on yet. Ok. Good. Well done. Let's look at the next case. Four. So final case of this talk. So Mr M OK. So this is the case. So a 67 year old man with a history of peptic ulcer disease presents with persistent vomiting. His ABG is as follows ph of 7.56 PC two of 5.0 po two of 10.7 bicarbonate of 31. A base excess of plus five other values are normal. So have a think about that. What's going on? Is there any compensation going on? Ok. I OK. The OK. Anyone else? Mm The Yeah, good. So yeah, well done. Yeah, it is metabolic alkalosis. OK? Because of the high Ph and then also the bicarbonate is very high. OK? P CO2 is not really significant in this case and this patient it presents with persistent vomiting. So as we said, for metabolic alkalosis, let's go back to this. OK. It could be due to too much acid excreted, which is excess vomiting. So if you do know what some of the examples of these key areas are, so that say metabolic alkalosis, acidosis, respiratory alkalosis acidosis that can help you. Um just to come up with your answer for an ABG. OK. So that is um yeah, that is pretty much that for case four, we've done case four and that's the end of the talk. Does anyone have any questions? And please do fill out the feedback um Before I will put it in the chart. Thank you so much. That, that's absolutely brilliant. Um Yeah, guys, just a reminder if you could put that feedback form, if you could fill out that feedback form. Uh The one that's just on the wrong hand slide. So that's great. That's for getting the note back and then at the end of this talk, um Well, it should actually be available now. Um You will have this feedback form um which if you can fill that out, that would be absolutely amazing. That will just give you access to the lecture slides, to the lecture recordings and to the unseen S pa s which um you guys have had throughout the day. So thank you so much to all of the lecturers for if you guys have any questions and please put them on the chat now or send them to the individual lecturers and just to remind you guys, we have the gastro all you need to know crash course coming up in a couple of weeks as well. So keep an eye out for that and make sure you attend. Thanks guys have, have a good rest of your day. Make sure you fill out the feedback form. Thank you. Bye bye.