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Okay. Okay, then. So, um hi, guys. I'm basically going to be talking through pharmacology today. Just, um, the just like a brief summary of a few drugs. So let's just get started. Yeah. So Hi, my name is a sheet for the or Sri, and I'm part of Brooklyn. Easy. So this is what we'll be covering in today's session, just like the basics of each. So keep terminology and said's cardiac drugs. I won't go into too much depth just enough so that we can, like, understand, and break it down one by one. Great. So the first one is key terminology. So before I actually start talking about the drugs, um, I want to stab lists. The main terms that we need to know in pharmacology. So the first one is pharmacokinetics. So pharmacokinetics is basically the movement of the drug within your body. So when you swallow it where it goes, where acts cetera, then the next one is started IQ index, which is a very high yield terms. And make sure you really understand this. The therapeutic index is basically the ratio of maximum tolerated dose. So minimum it's effective dose. So basically, how much of the drug you can give to the patient without poisoning them and allowing it to have its highest therapeutic effect. Then the next one is pharmacodynamics, which is basically how the drug works. So what part it acts on and how it's a tablet ized. Our next one is adverse drug reactions. So your address drug reactions are basically any harmful side effects as a result of taking the drug and finally, your contraindications. So your contraindications are basically anything that limits the user from taking the drug. So, for instance, aged. So they may be too young to take the drug, maybe pregnant, so they can't take the drug. They could be allergic to the drugs. Obviously, you don't want to induce an allergic reaction. So basically, contraindications are anything that limits the user from taking the drug. Great. So first we'll start off with our nonsteroidal anti inflammatory drugs and, um, analgesics. So I sort of created a flow chart just to make it easier to understand and to like, break it down a component component. So first we start off with our phospholipid violator. So an enzyme known as fossil I paid eight to will act on her phospholipid violator on released a molecule, Numbness or academic acid. You're our economic acid will then be acted on by another enzyme called prostaglandin age Synthes or PG HS. And this enzyme has two components. The Cox Domain and the Peroxidase domain. So the way and said's work are it's defined, basically, by inhibiting the Cox domain off the PHS enzymes. So that's basically the definition of a definition of NSAID, so anything that inhibits the Cox two main. So once you're PHS acts on our economic acid, it's going to release a molecule minutes. Prostaglandin age two or PG age too, which has three components. So that's gonna be your prostate gland and 82 or P G E, too, from bucks in a two and prostaglandin item or PG I to so your PDE to their main functions are paid. Facilitating pain, Um, allowing G I and renal protection and causing you turn contraction. So this component is the main one will be talking about for for the sake of NSAID, are there a box and a two and p g. I. To our may need to be with play that aggregation so remarks and 82 causes platelet aggregation and local nasal constriction on the way. I like to remember this is that T e x A to has letter A in it. So it causes platelet aggregation, whereas PG I to, um it inhibits platelet aggregation and causes local reason constriction. So the way I like to remember this is a PG I to has a letter. I in it so inhibits figure aggregation. Great. So, um, the three main and said I'm gonna talk about our profin aspirin and paracetamol. So obviously, if your cocks domain is inhibited by the NSAID No, um, the the roles that the P G two will not occur anymore, so pain will not be mediated anymore, which is why it acts as a pain killer on your you try and contractions will also be prevented. Your GI I and renal protection also not be present anymore because your Cox two main is being inhibited. And I'll talk about that a bit further and our adverse drug reactions. So, yeah, moving back to ibuprofen, aspirin and paracetamol. The way your ibuprofen works is it is a reversible inhibitor of the cox remains. So it competitively binds to the active site of the Cox Domain. Where's your aspirin? Would be an irreversible inhibitor of the Cox domain because it causes acid relation of the active site of cocks, which basically in simply, in simpler terms, it causes a confirmation. I'll change to the active side of the Cox two me, which is why it acts as an irreversible inhibitor. Now your paracetamol is quite a controversial one because, um, it's not really classified as an NSAID, since it doesn't actually inhibit the cox domain. Instead, it inhibits the peroxidase domain, but it still is termed as a pain killer, because I'm sure if you guys have gone for like over the counter drugs, if you have a headache, you can be prescribed paracetamol because it still does act as a pain killer is just not an NSAID good. So now the contraindications. So what limits the user from taking this drug so they're already on an NSAID. It's recommended not to be on a combination of incense. If they're pregnant, it can have a negative impact on the growing fetus, so it's not recommended to take it and said, obviously, if they haven't answered allergy, do you don't want to induce any allergic reactions on Finally, if they're under 16, so they're still developing. They're still neurological growth occurring, so they don't usually recommend you to take an NSAID if you're under 60. Finally, your address. Drug reactions. So, like I mentioned, your p G two is responsible for your GI I and renal protection. So if your cocks domain is inhibited, that means your GI I and renal protection will no longer occur. Which is why some of the side effects or adverse drug reactions include gastric alteration and bleeding or impaired renal function. Great. So that was just a beef, um, summary of what and sense in analgesia are and how they work. So let's move on to the pain ladder. So the pain letter is basically a concept that was established by the World Health Organization that basically stated that you should prescribe a drug based on the severity of the symptoms. So obviously the pain letter will start from your mild symptoms going to your moderate to strong, strong and in severe pain. So for your mild pain, you usually prescribe Passy, Tomorrowland and said's. And if that doesn't work and the the symptoms are getting stronger. You move on to cocoa tamal, which, um which is basically stronger than your paracetamol in and said's If that doesn't work again, you move onto weaker opioid such as a codeine and dihydrocodein. If that doesn't work, you move on to your stronger opioids itches a tramadol on methadone on find me. If none of this works and you're in severe pain, then the used i morphine fentanyl instead a shin. So the basic thing that you need to know from this is just the order in which the drugs occur. So if you're positive, paracetamol in and says don't work, what do you take your coat? A mold so you don't skip immediately to you're weaker opioids. You just go step by step up the ladder. Great. So I've just given an SBA to refresh your memory on what I've just talked in the previous slides. I'll give around 30 to 40 seconds. If a pole isn't launched, then you could just put the answer of the check. Great. So, um, lots of people are typing in the right answer, which is a code, um, also again, this is just testing your knowledge on the pain letter. Um, so obviously you're paracetamol didn't work. And the next step above that would be your cocoa tomorrow. Great. So now that was just a brief Sarria of NSAID analogy. Six. Now I'm going to be moving on to cardiac drugs, and these are the main ones I'll be covering. So before I actually talk about each of these drugs, I think we need to establish with the terms chronotropic I neutral bar. So you're chronotropic is basically your rate of contractions or your heart rate whereas you're on a trip is the force of contractions, right? So if you have anything that causes a negative chronotropic effect, that's basically anything that's reducing the rate of contractions. Whereas if you have a negative in a traffic effect, that's basically anything reducing the force of the contraction. So here I basically given a vascular smooth muscle cell on, but we have three drugs that sort of work in a similar way, So our first one is our organic nitrates. So all these drugs are basically given for people with hypertension or like high BP. So you're organic nitrates. What it does is it. It releases nitric oxide, which is a vasodilator, and what it's going to do is it's going to, um, stimulate your guanosine iculs cascade, which is a whole side Celtic middling cascade that you don't need him to be aware of. But you just need to know that once your bottle cycles is stimulated, it's going to increase your potassium if lugs, which will cause hyper polarization of the cell. So now, once you're sell is hyper polarized, that's going to reduce your calcium influx. And if your calcium influx is reduced, then you're going to have reduced amount of muscle contractions, which is what will ultimately lead to the basal dilation. So why does reduce calcium concentration? Reduce your contractions well, calcium during muscle contraction. Whether it's cardiac scan, little or smooth muscle contractions, it's It plays a very heavy role in the actual muscle muscle contraction. So it's released by your T to build on sarcolemma on. So if you have a reduced concentration of your calcium, then you're going to have a reduced rate of contractions. And obviously, if you're cell is no longer able to contract, it's going to cause these a dilation. So the next drug is your beta blockers, so in pharmacology. What occurs is you'll have very similar side effects is based on the class of the drugs, so your beta blockers, most of them, will end with the Suffolk soul. Also bisoprolol, metoprolol, atenolol and the way in which are better beat of lockers. Work is they reduce the electrical impulses am in a ting from your sign of atrial note, which means you'll have a reduced rates of contractions on what that means is it's going to act as a negative chronotropic. But it also reduces the county in concentration in your myositis. So that means it's going to act as a negative on a trip because again, if you don't have as much calcium, that means your force of contractions will also be reduced. So again, since it acts as a negative current trip on a negative on a tropical ultimately leads to vasodilation. And then your final one is your calcium channel blockers. So your calcium channel blockers, basically, I I think it's the easiest one to get your head around because it just prevents any calcium influx from entering the cell. And like I mentioned previously, if you have a reduced calcium concentration, you're gonna have a reduced rate and force of contractions on that's going to ultimately lead to visit violation. And an example of this kind of drug is doubt. Is, um, right? So now these final two drugs, like Randall and everybody's So neck around a lactose a coronary vasodilator. So it's basically used to park in any occlusions in the coronary arteries on a words quite similarly to the organic nitrates. So it again stimulates that guanosine i Clay's cascade, which will increase your potassium e flux, causing hyper polarization of the cell on this hyper polarization is going to reduce your calcium influx. And if your calcium influx is reduced, then you're going to have a reduced rate and force of contractions, ultimately causing raise a violation. And finally your I ever bribing, which is a rate limiters of acts as a negative chronotropic. You know, it decreases the heart rate and the rate of contractions on the way in which it does. This is it sort of prevents the face for funny currents, which is basically the sodium influx into the cell on go yet actors. A negative chronotropic. If the rate of contractions is limited than it answers a negative control. So yeah, this statement, it basically sums up this whole slide. So all these drugs ultimately lead to a negative chronotropic or negative ana Tropic effect that's causing nasal violation now moving on to or a sin hitters and diuretic. So again, these drugs are targeted towards people with hypertension or high BP. So before I move on to a sin hip bitters, I think we need to, um, go over the rest system, which is basically, um, used to facilitate BP or any changes in blood pressure. So, say, for instance, are BP drops. This will be sensed by ourselves in the Jackson Glomerular, a parentis which will stimulate your liver to release a molecule known as angiotensinogen. Now, once you're angiotensinogen is released, Brennan will act upon this and break down under 10 cenegenics 100 tens and one Brennan is released by the kidneys and then find me. You live your lungs release and you're tense. And one converting enzyme, which will convert your angiotensin 100 tens into now understands into has multiple effects. So the first one is it'll. If under tension too stimulated, it will increase the secretion of aldosterone in the collecting ducts ducts of the nephron. So if your aldosterone secretion is increased, it's going to increase your sodium reabsorption back into the blood. And obviously your water moves in the way in which the ions moving the same direction as the ions moving. So if there's an increased reabsorption of sodium, there's gonna be an increased reabsorption of water back into the blood, which will increase your blood volume on. Therefore, it'll increase your BP. So again I'll go over that again if that was too fast. So what happens is when you're angiotensin two concentration increases. Your aldosterone secretion is increased and so your sodium reabsorption back into the collecting ducts will increase. This will increase the amount of water that's for your absorbed back into collecting ducts, which will increase blood volume and therefore, in case increased BP. So you're a singer bitters. How they act is they inhibit the angiotensin one converting enzyme, which prevents the angiotensin one being converted to angiotensin two. So if that happens, then you're gonna have a reduced concentration of angiotensin two, which means not as much aldosterone is gonna be secreted from your collecting ducts between less sodium is reabsorbed back into the collecting ducts, and so less water will be reabsorbed back into the collecting ducts. This will be crazier blood volume and thus decrease your BP again. A sin hip bitters are given for people with high BP, so obviously the end goal is to try and reduce the BP. An example of an ACE inhibitor would be ramipril, and a common side effect is a dry cough. You also have your angiotensin two receptor blockers, or ARB so, and they work in a similar way. Except instead of inhibiting and enzymes, they're going to actually block the receptor that angiotensin two binds to. So if the receptors blocked and obviously again, you're going to have that reduced under tension to concentration on like I mentioned for for Before, it'll decrease your secretion of all go strong on go decrease sodium reabsorption, decreased water reabsorption decrease blood volume and therefore decrease BP. Good. So that's just a singer. Bitters and airbase moving onto diarrhetics. So, um, diet takes, most of them were working the same principal. The only difference is where they actually act in the nephron. So our first one is our loop acting diarrhetics. So furosemide, which is the most powerful one. Then we have our distal convoluted to acting diuretic such a spender from it aside and that those ones are moderately powerful. So they're not as powerful as on furosemide. And finally we have spironolactone, which acts on are collecting ducts and these are potassium sparing. So the way in which these direct six work is they block the sodium potassium chloride channels in the nephron. And so these ions or not being a re absorbed back into the blood. So again, if these ions are not being absorbed into the blood, then the water is not going to be reabsorbed back into the blood, which will decrease your blood volume and therefore the decrease your BP. Now your cable aspiring once act a little differently. So instead of blocking the iron channels to block the elbows receptors, so that means not as much. Aldosterone is being secreted. And so, if less aldosterone is being secreted, less sodium is being reabsorbed, so less water will be re absorbed on so your blood volume will decrease. Great. So I'm finally for our cardiac drugs are anti platelet, anti quieted and fibrillating drugs, so we'll start off with warfarin, which is an anticoagulant. The method of action for warfarin is that it's a competitive inhibitor of vitamin K, so Vitamin K is actually responsible for producing clotting factors to 79 and 10. So obviously a vitamin case and it is inhibited. Then it can't go on to producing these clotting factors, so this will reduce the rate or likelihood of clotting occurring in the blood. So your anticoagulants anti platelets, they're mainly given to people who face clotting in the blood. So you want something that will either break down the clots or prevent block a clock growth and development. So then we have a big shebang, which is another anti coagulant, so it also it also affects the clotting cascade. But instead of inhibiting vitamin K, it'll inhibit factor 10 8. So the role of factor 10 and the clotting cascade is the conversion of prodrome into thrombin. So obviously, if this conversion can occur than clots will not be able to form. So again, just to reiterate you're picks a ban, it inhibits factor 10 8 and factor Penny is responsible for the conversion of prodrome into thrombin. So this if this conversion can't occur, then clots will not be able to form, which is good because you're trying to prevent clot group. Then we have topical, which is an anti platelet drug. Antiplatelet drugs are basically ones that prevent platelet aggregation or platelets from clumping together. So they're a little different from anticoagulants in that anticoagulants work at a slower rate. And then finally, are fibula tick drugs, which is also place. So the way in which these work is if your clots have already been formed, they try to break down these clots to buy for been a lysis. So just to reiterate, they dissolve the clock by fibrinolysin. So they just break down any clots that are already been form. Great. So that was it for cardiac drugs. This is just another SBA to pester knowledge on that. Great. So I think I'll end the pole there since most review of started answering. So the answer for that was 15, um, warfarin. And the reason for that is because, um, like it says here, the patient should be given an anti coagulant s. Oh, I know. Some people went for a which is all the place. And I understand because you already have blood clots. So you want to try and break down these blood clots? But the main the main giveaway was that it said anticoagulants. And the only anticoagulate in this list is warfarin. So out alteplase is actually for being a little drug. Um, your beta blockers ramipril is for an elective, an arm or for hypertension rather than, um, any clotting induced diseases. So you hope that clear set up so just quickly moving onto respiratory drugs. So before I actually move on to, uh, these drugs, I'll talk about the innovation of the lungs. So our parasympathetic and sympathetic supply. So our parasympathetic supply of the lungs is mainly responsible for bronchoconstriction, whereas your sympathetic supply is responsible for bronchodilation. So the drugs that I'm about to mention are ones targeted towards asthmatic. So people who uh So if they're friends since exposed to an allergen, then they can have bronchoconstriction or they can experience bronchospasms. So you obviously want a drug that will prevent bronchoconstriction from recurring or will allow bronchodilation time curve. So our first one is beta agonist, so these ones What they do is they will stimulate the sympathetic supply so they will stimulate bronchodilation, um, and prevent any bronchoconstriction. So we have short acting and long acting beta agonist. So you're Sabah is salbutamol your labs or sell metro. And again, the way they work is they activate the sympathetic system to cause bronchodilation. And I am muscarinic antagonised work in exactly the opposite way. So what they do is they will prevent the parasympathetic system from being stimulated, so they will prevent bronchoconstriction from occurring. So again, you'll have your short acting and long acting must must chronic antagonised. So your short acting with the ipratropium and your long acting would be to drop the, um and again they block the person. But that extenuation those preventing bronchoconstriction. And finally you have fluticasone, which is just an anti inflammatory drug, and they're usually given in combination with either your beta agonists or your muscarinic antagonised, so they're not usually prescribed by themselves. Great. So now moving on to antibiotics, I think loads of people actually struggle with antibiotics, So I've sort of made, like, a visual way of learning it hopefully to, like, try and clear that up and make it easier to learn. So let's start with our first class of antibiotics, which is our cell inhibitors, or ARB eat a lectins. So, um, firstly, the structure here that I represented is your penicillin binding protein. So your function of your penicillin binding protein is to basically form cross linkages in the peptidoglycan layer of the cell wall of the bacteria of the bacterial cell. So how these antibiotics work is they have a beta lactamase things. So, for instance, penicillin, it has a bit elective bring that will bind to the penicillin binding protein and inhibited. So if your penicillin binding protein is inhibited, it can no longer serve its function, so it it will no longer be able to form these cross linkages in the peptidoglycan cell layer. So obviously, if these cross linkages are no longer being formed, the cell will weaken, and it will no longer be able to support the organelles and structures within the bacterial cell, causing the bacterial cell to just burst. So that's just how your penicillin, um, and your antibiotics, where your beta lactamase work. Sorry. So what happens in antibiotic resistance is that there's an enzyme known as beta lactamase, which will cleaved the beta lactamase that the penicillin and beta lectins use. So if this beta lactamase is no longer present than the penicillin binding protein continue to do what it's function is, so it'll continue to form these cross linkages in the cell wall and basically allow the bacterial cell to thrive. So obviously we don't want that. We want the bacterial cell today, So we humans have come up with a drug called Amoxiclav, which is a mix of clavulanic acid and amoxicillin. So what you're clavulanic acid does is it mimics the structure of the beta lactamase that penicillin and other beta lactamase drugs have. So it'll fool the little activities. And the beta lactamase will cleave the beta lactamase of the clavulanic acid rather than the penicillin, allowing the penicillin to continue doing its job. So, um, if the penicillin concurrent in you doing its job, then obviously these across languages will no longer occur in the cell wall, and so the bacterial cell will rupture. If you guys need me to repeat that, um, repeat the whole process again, I don't mind. But I just made a slide again, just summarizing what I said in the previous slide. So the way in which are beta lactamase work is they insert of beta lactamase going in the penicillin binding protein, which inhibits penicillin binding protein from doing its function on the main function of penicillin. Binding protein is to form those cross linkages in the peptidoglycan layer, so obviously, if it's inhibited, then it can no longer form form these cross linkages. And so the cell wall is too weak to support the structures in the bacterial cell, causing the bacterial cell to rupture and burst. So these drugs are termed as bactericidal drugs, which basically means they kill the bacteria. We have another type of drugs for Ms Bacteriostatic, which just prevents the growth of the bacteria so it won't fully wipe out the bacterial cell inside. It'll just prevent it from progressing into, um, basically prevents it from growing. More and more so. Examples of our beta lack times are penicillin, cephalosporins, um, black, a peptide. Such a bank of my sandwiches basically used to combat MRSA or the Super Bug. And they could be synergize with aminoglycoside and fluoroquinolones, which are two classes of antibiotics that'll come into the mix lights. But synergism is basically when you have a combination of drugs, they're trying to increase the therapeutic effect of the drug. So rather than just using penicillin alone, you can use penicillin and then aminoglycoside such a gentleman I sent to sort of increase that therapeutic effect. Finally, we have the anti antibiotic resistance that I mentioned in the previous slide. So an enzyme known as beta lactamase will cleave the beta lactamase thing of the antibiotics on what this means is the beta lactamase will no longer be able to inhibit the penicillin binding protein. But now we have a call, um, oxycodone, which is just a mix of clavulanic acid and amoxicillin, which will mimic the structure of the bait elect, um, ring causing the beta lactamase to cleave the Byetta like, um, ring of the clavulanic acid rather than the penicillin, which allows the penicillin to continue doing its job. So moving on then to our protein synthesis inhibitor. So here I just put a diagram of arrivals, Um, just to eight my explanations, but basically they have various, uh, being it's various components. And if even one of the sub units or components are inhibited or not functional that will prevent protein synthesis from recurring. And a protein synthesis cannot occur. Then obviously the bacterial cells will die. So our first type is our, um you know, Black decides which basically block the 30 s subunit of the bribes owns, um, and does preventing a bacterial protein synthesis on an example of this kind of drug would be gentamicin. So now, gentamicin when you prescribed it to older people, you need to be quite careful because two of the side effects is auto toxicity, which is just toxicity to the ear on, um, impaired renal function or being old damage. So obviously, with older people, they they are more prone to hearing loss and renal damage. So you want to be careful when you're prescribing. Gentamicin may be giving it in smaller doses. Um, and this type of drug would be a bacteria sidled drugs. So it's sort of kills the bacteria rather than just stopping the broke. Then we have our tetracyclines. So our tetracyclines block the a binding site of the ribosome. So if you guys remember from biochemistry, you're a sight is where your p r n a molecules bind and bring their amino acids to form the amino acid change. So obviously, if this a side is blocked, then the proteins and this is cannot continue to occur. An example of this would be doxycycline and these kind of drugs are bacteria static. So instead of killing or wiping out the whole bacterial species, they're just going to prevent it from growing further. Then we have our macrolides, which block the 50 s subunit of the bacterial bribe zones, and examples of this would be a bedroom, I said, and clarithromycin our macrolides have a very important feature where they can penetrate the cell membrane, which is quite important for intracellular bacterial infections. Such a chlamydia. So our chlamydia, it basically it sort of divides and goes intracellular. Really? So you need a you need an antibiotic or drug that can penetrate the cell number and so that it can reach the interest cellular area to sort of stop it from growing or to just completely kill it. And then finally, we have our chloramphenicol and our kingdom eyes in. So our chloramphenicol is one of the only antibiotics that can actually cross the blood brain barrier. When the blood brain barrier is inflamed here. Penicillin and your beta lactamase can actually cross the blood brain barrier. But usually it's only chloramphenicol, Which is why I come in practical cannot be given in high doses because it can obviously cause a lot of practice. It e on finally clindamycin So clindamycin. Um so one of the side effects is that you can get crossed classroom difficile infections, which predisposes you to pseudomembranous colitis, which is just a fancy medical term for inflammation of the large intestine. Great. So now moving on to our DNA RNA, since this is inhibitors. So let's just I've given this sort of diagram to help me explain it. But basically what it does is it inhibits an enzyme numbers topoisomerase and papa summaries. It's main function is to unwind the DNA. He likes to allow the replication to occur. So obviously, if you're told by some races inhibited, then your DNA headaches will not be unwound, and so DNA replication will be prevented or just cannot occur. So these kind of drugs are bactericidal because DNA RNA synthesis is just completely stopped. Um, and examples of this would be if your kid alone's nitrofuran Toyne metronidazole and refund person finding moving on to herself undermines, which is the last class of antibiotics that will be talking about is the way they work is they inhibit Floyd synthesis. So I didn't until I made these lies. I didn't actually know what full it was, so let's briefly talk about what fully is. So what full it does is it donates a middle group to yourself, which is, um, a base. It's an RNA base on. Once it donates, it's middle group to your silk, it converts the yourself A dining on. Timing is a DNA based, So if you're full needs and this is cannot occur, then your RNA cannot be converted to D in it, which is why it is required for DNA RNA synthesis. So in a way, um, the cell phone in mind if they inhibit for folate synthesis, they also prevent Deanna and Arnie synthesis from occurring. So these kind of drugs are bacteria static, and examples of them would be a trimethoprim and sulfa med box is all, uh, trimethoprim can be used for uncomplicated UTI is, but usually people use nitrofuran point for treating utx. Great. So now just another SBA. Based on those things, I think this one is a slightly harder one. I'll give you guys 30 to 40 seconds to answer it. Great. So I think I'll end it there. You guys pretty smashed it. Honestly, Um, if the answer is for from passing, um, think that's be on. The reason for that is because, um when you take her family's in, it's sort of causes the liver to release an enzyme that breaks down Easter Genetic faster rate on your birth control and contraceptive pills usually try to increase your estrogen concentrations. Obviously, it's a contract it. So that's why they try not to give her family's in along with the contraceptive or birth control pill, because it basically just breaks down the surgeon at a faster rate. Great. So now moving on to our Alzheimer's drugs? Um, before I actually talk about the drugs, let's talk about what Alzheimer's actually is and how it's caused. So your Alzheimer's, what it is is it's basically a last a lack of a subtle colon in your neurological and cognitive function, So acetylcholine plays a very important role in your cognitive function. Um, it causes motivation, memory, arousal, attention learning. It just plays a huge role in all of that. And so if you have a lack of acetylcholinesterase to decrease your cognitive function, the way this happens is there's an enzyme known as a seat of acetylcholinesterase, which breaks down your acetylcholine. And if you're a silicon and it's broken down, it can no longer. They can no longer play its role in your cognitive in urological function. So the way we tried Teo contract the Alzheimer's from occurring is by using acetylcholinesterase inhibitors. So these inhibitors, basically they inhibit the acetylcholinesterase enzyme, which then prevents the acetyl colon from being broken down on. This will then increase. Acetylcholine is half life so that it can continue playing. It's role in cognitive function, so things like memory, um, memory, learning, arousal, etcetera. So we have the way they prescribed the drugs is based on the severity of the symptoms. So, for first, the mild symptoms you're giving a drug room is donepezil. The knee, a mild to moderate. You're given gallon to mine and resting mean, and then finally, for your moderate to severe, you're given memantine, so your first two of the mild to moderate symptoms are a acetylcholinesterase inhibitors. So, like I like I mentioned the previous slide. They inhibit the acetylcholinesterase so your acetylcholine cannot be broken down, which increases the half life of acetylcholine so that it can continue to play its role in cognitive function. However, your moderate to severe so amendment team is actually an acetylcholine receptor blocker or antagonist. So you're probably thinking, isn't that country into counterintuitive because you want your seeds or colon to bind to this little cold in receptors so that it can play its role? But actually, if you're a sickle on receptors are blocked. What happens is your brain type tries to compensate, and so the increases thie or operate up regulates the amount of acetylcholinesterase brain. And so it sort of acts as a positive feedback loop. So again, just to reiterate that what happens is your acetylcholine receptors are blocked, and so your brain tries to compensate for that by increasing the concentration of this it'll colon. So it's sort of acts as a positive feedback loop. Great. So now finally, this is the last class of drugs will be talking about antacids, proton pump inhibitors and age to receptor antagonist. So these stores are mainly used to treat acid reflux, and it's just based on the Celebrex. A very piece of the first one is our alkaline antacids. So this is usually stuff you can get just over the counter, things like Gaviscon Rainey's Milk of Magnesium. Sure, you've you guys have heard of all of this on the way in which they work is they contain magnesium and calcium and they sort of mutual eyes your gastric acid s so that it doesn't cause that burning sensation of acid reflux. Then we have our H two receptor antagonist. So before I go on to how these work, let's talk about how gastric acid secretion actually occurs. So your gastric acid is actually secreted from the parietal cell and you have these H two receptors where histamine combined too. So once your histamine binds to your age two receptors, it increases the concentration of camp in your guest in your bridle cell. If your camp is increased, then it'll stimulate the age plus cape list hydrogen potassium ATPase pump to increase your age plus secretion. And if your age prosecution or your hydration secretion is increased, it will bind to the chlorine islands and the Lumen, which will increase your gastric acid secretion overall. So the way in which these H two receptor antagonists work is they block the H two receptor, so assuming can no longer buying to the receptor, which means your camp will decrease on. This means that your HB a secretion from your hydrogen potassium ATPase pump, will also decrease, which will done overall go to decrease or gastric acid secretion. So examples of these kind of drugs would be ranitidine cemented in from what I mean, and that's it. And so the common side effects for HMOs after antagonists is to be, um, now I've written and a neural ranitidine because it's no longer being sold or prescribe because it was found to have crossed the carcinogenic effects. So just something to be aware of so carcinogenic effects basically means anything that increases your likelihood of a risk of developing cancer. And then finally, we have our proton pump inhibitors. So how they work is they inhibit the hydrogen potassium ATPase pump, which means that it'll decrease your hydrogen secretions so less hydrogen will bind to the chloride I owns and the Lumen, which then goes to decrease your gastric acid suppression overall, um, so examples of these kinds of drugs would be a Meprazol and lansoprazole. And so, just to be, it's right. They block the hydrogen potassium ATPase pump, which means less hydrogen irons will be produced so less HDL secretion will be occurring from the parietal cells. Great. So I hope I didn't go too fast and that, but that is my last slide. So I hope that was really helpful for you guys. Please do fill out the feedback for me if you want the I first to the slides. And yeah, these are my references, so I'll just pass it back on some. Meghan, Thank you so much. That was ready. Good, Ready, Comprehensive. I've popped in the chat as well. There's the link to the feedback form, which we would love You guys ought to fill out. I've also put a link into our pre kidneys e mailing list. So if you want to get notified by email before our sessions, then I'm just feeling your details and we try and send emails out before each of our sessions to remind you with the ceilings, I'm just going to start sharing my screen and we'll go through some embryology, just finish off. So I'm not gonna be just going through some embryology. For those of you, that card of students entering here to this session will give you just a small introduction to get you a a step ahead, ready for K seven. But if you're not a card of student equally, this will be a really good introduction, hopefully to really Gee. So these are the topics I'm going to be covering today, but let's get straight into it. So I'm going to start my presentation by just stuffed. My starting point is going to be the end of sexual intercourse. So at this point, the gametes have been formed. They're starting to move together. S so you've got the you site or the female gammy, which is being wafted by ciliated epithelium towards the cavity of the uterus and the sperm, the mail gammy, which is swimming towards and into the you trying to so asparto, the star of early embryonic development. There are three main reactions that you need to know which occur before and during a personalization. So the first one I'm gonna go through is the capacity a shin reaction. So the capacity a shin reaction occurs as the sperm move through the female reproductive tract after ejaculation. And it's the last step in the process of sperm maturation before first ization takes place. Not at this point, you need to remember that Eastern is the hormone that's predominantly produced in the 1st 14 days of the menstrual cycle on bats in the run up, the ovulation. So when the PSA is released on the days when the female is the most fertile, so Easter gyn is, what it's turned is doing at this point is it's stimulating secretions from the walls of the uterus and the's secretions are really important because they destabilize the plasma membrane surrounding the head of the sperm on that causes the removal of the washing off of black of proteins, cholesterol on other proteins as well, from the plasma membrane of the sperm overlying the Aqua zone. Now, the Actos, um, is a really important structure that will come up quite a lot today. On this is a cap light structure covering the tip of the sperm head, which contains lots of hydrolytic, um, enzymes. So when this washing off takes place. This exposes the acrosome underneath, ready for the next part in fertilization, which is called the acrosome reaction, and only spend that of undergone capacity. A shin in the capacity a shin reaction compacts through the Corona Radiata, which is at the outer layer of the you site on undergo the next reaction as to say that present reaction. So just to recap, because I know this is a new topic for cardio students. So the capacity a shin reaction is the removal of the washing off of the glycoprotein, the proteins and the cholesterol from the head of the sperm. So now let's move on to the AC. Resent reaction. So in that prison reaction, that's both of undergoing capacity. A shin. They got rid of all those annoying proteins that are in the way. On they push through the Corona Radiata, which is a said, is the outer layer of the site on what they then do is they bind to receptors called Z P three receptors on the zone of police. It er now the zone A police stir is another layer to the site, and it's a glycoprotein layer sitting just below the Corona Radiata. Now on this phone need to bind to this receptor to ensure that first realization is occurring between two organisms of this paint same species. So it's a really good failsafe mechanism is different species. We have different receptors. So to make sure that fertilization is current between two humans, this band binds onto the CP three receptor. Now when the sperm binds onto the CP three receptor, this causes that acrosome with the hydrolytic enzymes in the spans head. To release those enzymes, the hydraulic hydrolytic enzymes released um, and those include like proteases, for example, to break down proteins. And what that does is when those enzymes are released. It creates a hole in the zone, a booster for the sperm to tunnel through. So to recap, the acrosome reaction is the release of those hydrolytic enzymes from the acrosome in the head of the sperm after finding to the Z P three receptors, allowing it to reach the cytoplasm of the use of underneath. Now find a reaction I want you to know about is the cortical reaction which, because when one sperm touches the plasma membrane of the secondary of the you site, so the president embrace laying just under the Soma police. Does he have the Corona Radiata Zone? A. Police starting in the president membrane and when that's bone touches the past remembering this opens channels on that memory and that causes positively charged sodium ions to flow into the site. Onda change in membrane potential that occurs there because you're having that movement of irons, repels other sperm and stops another sperm from binding to the plasma membrane. And that's really important because that could, if you have multiple sperm combining to the buzzer membrane, that could lead to something called police for me, which is basically the entrance off several sperm, several spermatozoon into one egg. Um, and this process of changing the membrane potential to repel of his thumb is called the first or the fast block to police for me. And that's because that's really quickly. It's a quick change in memory potential on it's the first attempt to stop multiples firm entering the site. So at this point that you cited the sperm cell membranes, fuse together, and that allows the sperm to release its haploid genetic material. So haploid referring to 23 creams and instead of 46 into the use I Now, as the stones genetic material moves in into the side president, the site it triggers special Granules to fuse with the plasma membrane of the site. And what that does is it releases enzymes from those contained within those Granules to break down the Z P three receptors on the zone, a police state that were critical to the acrosome reaction I just spoke about on This means that no other sperm have any ZP three receptors to attach to azelas breaking down those receptors. It also helps the holiday and the president membrane on that process of releasing those enzymes, making the present membrane hard on you not having any ZP three receptors. It's called the slow block or the second blocks. Probably spare me, um, illnesses because it takes more time. Um, it's much slower process. So, as I said, blocking smallest for me is really, really important because it can lead to cycle polyploid e, which is when you get a cell or nucleus containing more than two sets of chromosomes, and you want to stop that because that's not viable. You're not going to get life from that in humans. So to recap, the cortical reaction is the process of preventing police for me by the release of those Granules too hard in the plaza memory of the site on by the slow book and changes in the membrane potential by the parts faster. So when the genetic material off the female or male gamete is combined to form one cell, it's going to now be called his I go on that now has 46 chromosomes in it, a disappoint. Fertilization is complete, and a rapid cell division begins on this rapid cell division after the prednisone's of mixed together is called cleavage. However, the cell cycle during this process of cleavage is different toe what normally takes place when, ah, normal body cells divide. So just a little recap of the self cycle. There are four stages two mg one, the cell grows and Replicators organelles. Then end his essays Where be being a replication of us? Then? This out into the faithful G two, which is another growth phase where the cells increases in size. It makes him protein so that it's ready for so division, and then after that it goes into envies, which is mitosis insider kinesis, where the cells chrome zones inside to present divide into two daughter cells that are identical to the original. So no in cleavage, I said, This is slightly different on That's because the cells skip G one and you, too. So there is no cellular growth between each division on the cells rapidly alternate between synthesizing new DNA on but undergoing my toast. It's just that that into daughter cells. Now, as this division, because of just rapid, you're rapidly building new DNA and then splitting yourselves. You get very, very rapid cell division on so initially, this forms to cells and 12,016 cells. Um on each of these individual cells is called a blastomere. Now, at the 16 cell stage, which is is about 3 to 4 days, post first is a shin. This bowl of 16, roughly 16 last um, ears is called a more regular now once the more you'll of um, forms. Something called compaction occurs now in compaction. Some of those blasted is tightly adhere to each other, and they begin merging with each other, and they create something called the out to Selma's. Meanwhile, another group of last mayor's begin to migrate to one end of the cell, creating something called the NSL mess masses. So I'll go over that again. So the you what cleavage? Rapid a rapid growth. But there's no growth. It's just rapid. So division, um, you. So you're rapidly dividing themselves to 48 16. When you get 16 cells in each of those cells, it's called a blast in it. When you get that full of 16 cells, that's called a Muga compaction, then because where you form an outer and inner cell mass as the cells get closer together. So we've said that one of those, some of those boss made a migrating to one and itself creating the N s a mess. So the spaces between those Boston it as that compaction is occurring, decreases on the spaces between the inner and outer Selma's, um, accumulate basically to form one really large cavity inside the structure on, um, as you can imagine, all those spaces, a kind of aggregating into one area. Water also passes through the outer cell mass into this area. On this form, something called the blast is this cavity, which is this kind of blue area here on my diagram. Now, once this is complete, it forms something called a blastocyst. So the blastocyst, as you say it's from from the inner Selma's, which I'm now gonna call the embryo blast. That's because after after some further differentiations and further specialization, the NSL mess them gets refer to is the embryo lost? And that's the big that's coming from one side. And then you have the out summer, which is now called the Trophoblast, after of similar for the differentiation and that's forming the ring around the outside so that glass is is formed about 5 to 6 days. Post 1st, 1st is Asian, but it's still contained within that zone. A police stir that we spoke about earlier, which was the glycoprotein there, which originally had the Z P three receptors on. So to implant successfully in a female's uterus into the endometrium. The process it's needs to a hatch out or escape out of the zone of pollution. Now, proteins expressed on that out of cell mass, or is, it said, now called, the trophoblast layer of the buses allow it to attach to the endometrial of the uterus. Eso you've got proteins on there, and they are able to grab onto the endometrium. Um, without this, you'll find that the attachment off the off the process is to the endometrium fails and said the embryo will be lost. So those trade for ourselves. They wrapped into the end of endothelium, the stuck with the endothelium. Once they've attached, they start to pull the blastocyst into the underlying tissue. And at this point, the trophoblast cells then different you into two different collections or types of cells. So you have the cytotrophoblast. Now this cell type is you can see the individual cells in this cell type, so it's a collection of cells, and you can still individually make how each type of cell and this is the closer of the two layers to the embryo blast of the end of semester. We had our in a cell mass on the inside on one side. You then have the cytotrophoblast closest to it. A bit further out is our second layer of the trophoblast, which is called the same city. A trip for bass and as the name suggests, this forms of sin City, um, which basically means a single mass. It's like cytoplasm. So they're the cells that are making up this layer. Their cell membranes disintegrate on. They form a single mass, basically a single mass. It's like cytoplasm on The sensitive trophoblast diet aggressively invades the cells of the lining of the uterus. And eventually, on this in city, a trip last form, finger like protect projections, which reached a blood supply from the mother's blood supply to the uterus and eventually that goes on to form the placenta and supply the embryo with the nutrients it needs. This in city, a try for bus is also really important because it produces beat up HCG, which you may have heard off before on what beat HCG does. Is it signals to the Corpus Luteum, which is going back to some like reproductive physiology, is kind of the remnant left after ovulation. So after the egg leaves the ovary, the corpus Luteum is left on this. Since idiosyncratic balls produces the hates TG, which signals to that corpus luteum to keep producing progesterone in order to maintain their endothelial lining, make sure that it's not shed because if you can imagine if you lose that progesterone on the endothelium is sheds. Um, then you're gonna shut the embryo with it, and you're gonna lose your everywhere. I'm finally just complete. Implantation is usually complete by about 10 to 12 days. Post rest is a shin. So I realize that's a lot of new words, probably for a lot of you. In a lot of it could be a definite difficult on Sand and Realogy sometimes. So let's just recap. So the NSL mass that we had in the in a bit of our processes, different shapes and becomes more specialized on then gets turned. The embryo blast and this will go on to form the embryo, which I'll go into shortly the outer cell mass. Different. Jason becomes more specializing. Gets turned The trophoblast um, I'm from here differentiates into two different type cells which we said that side too trophoblast on arm or invasive since city a trophoblast, which both together go on the form parts of the placenta. So I'm now going to go into a process called gastrulation, which is really important in the formation off on embryo. So gas relation is defined as the process in which a trying a am try lamina embryo so made of three layers forms from a bile omitted laminated disk. So basically something with two layers. So let's break that done. That's explained how that happens. So the embryo blasts, which I said earlier came from the inner cell mass, has two layers to it. It has something called the blast and has link all the hype of last, which you can see in blue and green on my diagram on that together, the epi blasting the hyperplastic other is what's termed the bile am in a disk by meaning to lamina mean meaning layer, so it's got two layers to it. Now the star of gas relation is seen or is noted by the formation off a structure called the Primitive node. In the primitive streak on this occurs around 16 days post fertilization and these two structures are formed. A. The Kordel, or the bottom end of the Brilinta disk on these primitive structures form the body's access. So from Master Annus, the access is kind of in that line, which is formed while that primitive, streaking primitive note. So what? All the permitted street in the moment, if I'd The primitive streak is a thickening off the epi blast cells. So the blue in this diagram in a line basically it is a thickened line of the epi blast air, and the primitive node is very similar. It's a thickening, but this time it's a circular thickening of fubar cells at the cranial. When's that ahead And if you like, off the primitive streak. So this being your primitive node here, the cycle and in a primitive streak is this line here? Yeah. Now, after this thickening has taken place. The people are cells at the center of the structure of these two structures die which now forms the primitive groove on the primitive pet. So the primitive streak said the line the center cells die on. Then that becomes a grief on. You had the primitive note on when the cells die, that becomes a pit. So you're for me a space where the dead cells were basically so after these EpiPen ourselves of dye have died nearby. F u ourselves now start starts of creating a chemical called five grass grow growth factor eight laterally. So they're releasing this chemical and they're pushing it out to the sides. Basically. Now this fibro grew up fibroblast very fact eight is really important because it binds to Ecuador cells lateral, the way it's being released. So to say they're pushing it actually on that in him, it's the production of something called EKG. Had Herren's now eat cut. Here is a really important molecules on their adhesion molecule is that allow everybody sells to stick to the neighbors? Basically, So they're like adhesion miracles do they keep keep cells together. So if you're releasing this fiber grass growth factor eight and that is inhibiting the production of the cat here in's, these people are cells can now detached from each other. There's nothing holding them together. So then what they start to do is they start to full down. So I kind of I've kind of showed it on this diagram. Here they begin to full down that groove in that pit, Um, I showing on the image. Now what happens is as they fall down, these detached epi bar cells replace the hypoblast layer to form a new layer called the end of the end of the term. Sorry, that's not correct. With slide in the orange, that should say ended. Um, so to emphasize the hype of ourselves are replaced. The hope of us don't form the end of them. It's from the epi blast layer. But the epi blood cells are going to replace the hyperplastic cells to form the end of them. The epi bus continue to make more fiber grass growth factor eight. So more people are cells, fall through that gap in the same fashion and then make a middle a, uh which is called the Museum. I'm finally the Epitol still remaining is then turned the Actos. So this creates are try lamina embryo. We've got off relations, the extra derm, the means a derm and the end of them. And therefore now we've got all three layers and we formed out. Try lemon, a embryo. The process of gas relation is complete. So here's a little update version of our treatment. Um, so we know that the embryo grows different dates to form. We've got the bile a minute embryo, which is made of the epi boss and hypoblast, and the epi blast name goes on to form the three. Germany is the active down the measles, German. The end of them. The hypoblast doesn't for many of those three layers and its cells instead replaced by ended, um, which is derived from the epi blast air. I hope that makes sense. Guess relation is quite a difficult topic, so I hope that helps out. So we've got these three layers. Great. What's the point of it? So those three generators are really important because they go on to form different structures in the human body on it's really high yield to know some of the key structures that they're going to fall now. I'm not gonna run through all these. Now you will get the sides. But as a general rule, the extra dumb developed into our nervous system and any sensory organs that basically collect information about the outside world. So, for example, are epidemics are central nervous system peripheral nervous system, the lens in the retina in the eye. They're allowing us to collect information on the outside world world. Therefore, they're derived from the accident, and you have the means a dumb. This develops into structures maybe in the middle of our body related to the musculoskeletal system. So our bones and are three types of muscles as well as the genitourinary system such as our kidneys, our bladder And finally, the end of the, um mainly developed into our GI tract, um, our long digestive tude and all the organs coming off of it. So it's just the lungs, the liver and the pancreatic sector. So that's a scar as I'm gonna go today in terms of content, hopefully card of students. That's giving you a little taste of what's to come if he hasn't scared you, and it's just giving you a little bit of a heads up. If anyone has any questions are answered after this s t a certain gonna launch a pole where someone could launch the port for me. So an embryologist quizzes your knowledge of embryology and tells you about a recent recent patient case she saw about a patient who developed a condition under the umbrella term of gestational trophoblastic disease, or Duty day, the cells causing this disease and not part of the lineage yourselves that go on to develop into the embryo. So based on that description, which of the following day is is the most likely causing GT Day? You could just pop it in the chart. If the polls are working the bone should be always the poet. Okay. I can't see the pole. Sorry. I don't know why it's not coming up my screen, but yes. Are you Are you able to see the results? Know? I know. Okay, I'll call it in about 10 to 20 seconds. Okay. Um, I've just seen runnin your question on the chat. Is the music term formed from everybody sells to? Yes. So the epi blast forms a love the three germ layers in the trial. Um, embryo, my Oh, reveal the answer. Now, if that's okay, um so well done to those of you that today, that is the correct answer. Eso the question stem. If we break it down, explain the cells involved in the paper. Physiology behind GTD do not form one of the layers of the embryo. I'm going back to ourselves. Need you're not on our tree map that we had into the blastocyst from the Selma's. That's the collection of cells towards the one end of it on the outer cell mass, which is the ring around the outside. We then said that the NSL mask different shapes to form the embryo blasts, which then goes on formula embryo and the number of embryo blast is made up of two layers are by 11 or disc Our last note hypoblast and the last thing goes on for more freedom layers off the train a minute. Embryo the actor down the metered. Um, in the end of them. Therefore, option A, B, C and e a lot of the lineage of the embryo. However, the outer Selma's, um, which was the ring from the glass assist, um, forms the trophoblast um, which is a little bit of a clue in the name of the condition. And we said that further different rates into decide to turn balls in the city of her for boss, which both going to 4% of rather than the embryo to that full D is the correct answer. So thank you so much for this thing, his all our dates again for our future sessions to say this teaching was just a taste or into embryology. But if you'd like to know more on this topic, dryness for our session on the 11th and where will be Bill will be building on what you just learned. There's a set. Facebook event will go up shortly and for cardio students, the sessions about basic clinical sciences are to do with your PCs Onda Final plug. If you could fill out the feedback forms, that would be much appreciated on. I just want to have big thank you for joining us back to school. Siris. We hope it's been really useful, and we can't wait to teach you some more during the second year. I hope that's help loads of you. If you guys can share our our events that that would be amazing. Um, yeah. And, uh, at the beginning, we put out a call for ah, university representative. So if you guys I want to be a reunified city representative representatives, we have a few spots open. What? Yeah, initial. You still there? You can stop the recording, Megan.