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Okay. That's just s 0 100. Emily know he's going to start. I'm heartbroken. Physiology off, aging family. Sign it. I'll, um I am here. Talk to you today by aging frailty I'm prescribing for the field elderly. A subject close to my heart. Yeah. So what we're gonna try to do today is think a little bit by a gyn aging, um, going to talk about the physiology of aging because I think it's really important to know what happens to our bodies that we can understand some off the pathological disease process that we go through. We're going to talk by what frailty actually is and what it means. I know you've covered it that already, but we're gonna talk a lot more about that. And then we're gonna talk about prescribing in the field elderly because there are special considerations there. We're not gonna do it all at once. We're going to stop after shot, but physiology for coffee, because it's quite a lot to digest. Okay, So why do we need whatever all this? Well, the world is growing old. And for all you working in need, either will not come as a shock. Um, the last 100 years, there has been a dramatic rise in the elderly night. Currently the wh you still climbs. The elderly is over 65 but it's being changed. The elderly will be over 75 middle age. Most my mother specifically was very happy to know has been extended to 75 on the old old, which is currently If I was over 75 will be over 85. We sort of better medicine, better sanitation, better housing we use the population are getting are able to live longer. Um, not just our population, but the population all over the world over 60 is going to double in the next 30 years, which is gonna massively change the medical needs in all countries. Um, the old old over 75 but really over 85 is rising very rapidly. Um, they're probably going to double the initial estimations over every 30 years. It's probably gonna be a little bit less than that. And in the UK, specifically, people aged over 65 I those who retired, none of us are gonna be retiring at 65. Um, not right. Number those. You're still in education, which means that we are probably gonna have a very mushroom shaped, um, population, and that's gonna have huge, huge criteria for work force for caring, especially. And it's gonna make us need to think about where we're going to care for our old old are freeloaders. Let's talk about what happened. This is the age. So we changed from the sales up. Our self physiology changes are tissue structures change our immune response changes. So our ability to respond to you in threats changes homeostasis where the body's ability documented and it's internal, um, environment changes on there's big changes in formal pharmacokinetic pharmacokinetics informative Deconamine. I eat what drugs do the body on, what the body does two drugs and we're gonna talk about that as well. So that's talk about the aging sale. So most embryonic sales conveyed about 50 times on. Obviously, as we get older, our sales get older, too, and they can't divide as much. Previously, we thought that some sales, like my cardio, um, you're on's didn't replicate on those cells. They did last a lifetime. But the more we learn about it, um, microscopic cells, the more that's probably not true, and actually, we do get some urine regeneration. You do get some cardiac generation as well. So some. There is some replication in these cells that you thought previously didn't replicate. High day cells replicated. Um, so we're talking really about cell division, going back to biology for GCS and level, which for me was about to go nine. So chromosomes need to be on zipped in order to be replicated at the top of each chromosome. You've got your telomeres, but it's you're sort of nonsense DNA, which is there to protect the coding. Deanna Till, uh, Maria's is the enzyme that actually is supposed to protect your telomeres as a rep. With you, it's, it's back up on it protects the teen years. Unfortunate. As we get older artillery, a Z gets less active and is less useful on back. Chew away this convicted Tina shortening, which is what is associate it with aging. The signs of aging me see an office with your disease. Because this process get, sources may get older. You get unemployed. A variable comes, um, numbers in different sales on this complete two things like cancers that we see more of an older age. You also get increases in usually rely, which are a little mini Get the I making have root DNA in them which can can lead to run themselves vision. Um, I'm constantly generation. Our sales are generally quite good at dealing with free radical damage. And again, as we get older, we're not able to do this so well, we're not able to mop up our free radical swell on again. If our sales are vulnerable to damage, they're more likely to display of normal characteristics and again come turned towards cancerous changes. We use on my back on real itchy and to make energy to get our energy from food breakfast again, this gets less efficient, we get older. So what we put in when we're 50 number 20 you're not gonna use the same way, and you're not gonna get out. So you actually are going to be changing the way your body metabolize things because off this chair and breaking going on, that means you're much more vulnerable to small changes. A lot of the lies assumes that we have in our cells, which was supposed to help break down fats still working as well on you actually get a little factor. Opt. Let's pull like a few skin, um, gathering up in the sales. These are late two things like Alzheimer's Parkinson's macular degeneration and are actually a really, really big topic. A moment for research. I want to talk about cells, in essence, because this is probably the thing that is causing the free allele daily symptoms that we're seeing Sales, in essence, is what happens to our sales actually stop dividing. So when ourselves are no longer useful, they're no longer working. They are spokes to undergo apoptosis, like the very old summarize they're supposed to fall in their swords on their spoke to do the honorable thing on commit suicide when they're no longer useful. Sometimes genetic changes means that sales don't actually have able to do this instead of being cleared up. I'm getting bingo, you know, being got rid off, they stop dividing. But instead of going away, they actually just sit there really common in adipose tissue, um, on the skin as well. So you have these suggested sales are no longer useful. They're no longer dividing or no longer actually contributing to healthy tissue. But they're sitting there on they still secrete things like side of kinds. Both factors funny proteases. And this is like a secreto called S E S P. This is associated with all the things that we know in family sided kinds. Do so that can be associated with, um, information they can be associated with, um, auto immune disease. They can be associated with, um, free, radical, damaging things that that as well. So what's supposed to happen is that natural killer sales and macrophage were supposed to come along and clearly senescence sales. But sometimes this doesn't happen very efficiently. There's some really interesting research going on a moment where they're looking at nice on they have in Some mostly have managed to enhance the natural killer cells so that they are able to find these nests in sales more efficiently on in other mice they have completely knocked out. It's the ability of the immune system to clear them. So you have some super mice who have very efficient clearance of your senescence. Sales on you have some mice that don't clear them a tall so these mines, all on average, will live about the same age. But the super nice, the ones who can really clearly, really well, clearly. Snacks and cells. They are the major Rebus lights. They are, you know, the body builders of the mice world. They are, you know, they have good teeth. They have good hair. They have good cardiovascular function. The most don't clear the Cenestin tissues. They are the free lights. They have no muscle mass. They're much more susceptible to disease. They do tend to die earlier. A little bit, some of them do have two, roughly the same age is that is the good nice. But it's just proof of showing that, actually, this is probably where the frailty syndrome is coming from on. It's really interesting area of research. So what happens to are connected tissues? We get older. So a lot off the changes that we see associated with aging and, um, frailty are actually because of our connective tissue changes. So we get stiffer. I'm definitely getting stiffer. There's loss of assisted eight, so the collagen molecules, instead of sliding across each other, become linked with sulfide bonds on. That makes us a lot less supple, so it's a bit like when you wet leather and liver opens sun. It becomes much more, um, rough and crackly. And it doesn't start stretching. Go back as well. So if you think about it James of aging. So we think about the changes that we see in our skin. Um, loss of colleges in the scheduling of the wrinkling and changes of aging, which is obviously something off Crestor. Um, you think about our vision. The loss of elasticity in the tens of the lands means that we often become much more excited because we come to actually adjust our land size in the eye. And that changes our vision as we get older. If we think about our blood vessels, they lose their elasticity were more likely to get hypertension and cardiovascular disease and three progressive disease. Our tendons aren't as good. So instead of actually being able, Teo very quickly snap back whenever say, we have a stumble or a trip. Um, instead of being able to tense, are muscles tense Encore So that we stay upright. That happens much more slowly, and we're more likely to fall on. That leads to a lot of the problems we see associated with Real Elder. What about aging? An immunity. So as we age our famous becomes smaller and eventually disappears. This actually start really early on in life. But there is still some fine making a time make involvement even in sort of early middle age. Unfortunately than R T sales do not work as well as he did. So you can get reactivation off infections off childhood. That's really important in the elderly. The moment I think as we clear things that tuberculosis, it'll become less important. But no, I I This is why we started to see in the feeling old people, you cannot get reactivation off. Disease is off early age, such as TV. Um, it has to be a plus side to everything was always a glass half full approach. You do get less Still a type. Hypersensitivity reactions. Um, are you tomorrow quite often becomes less efficient. It gets more fibro's. You don't produce your B cells so well, you're mature. Lymphocytes are already circulating. Stopped working so well. So you're not actually going to make the same antibodies that you did, Which is why you're more susceptible to things like flu, even though you may have had them when you were younger. A swell um, you will get more or 20 but he's produced some of this is uncertain whether it actually has any change in physical functioning, but it just is a sign that our immune systems are changing. Um, you get much, much more likely to have things like cll CML, proliferative disorders of lymphocytes, and, um, when I see just generally different sorts of fun, immunological malignancies, all those overall taken together means that we are not able to respond to the same way as we could when we were in her thirties twenties forties. To me in challenges on, I think we have really seen that the last year we've really seen with corporate, we're really seeing high, much more effects, the feeler, more elderly population. And that was a little that there, so homeostasis or the body's ability to maintain its own internal environment is really important. Home is this is the age also breaks. Doing on this leads to a lot of the problems that we see with the free level daily. Um, if you think about your sales, you need to maintain your pH very, very carefully, so your enzymes work. You need to be able to maintain your temperature There's lots and lots of different ways that we do this. Some of the hormonal feedback systems that we have don't work so well. So we actually end up a lot of the time with excess cortisol from our So they city age cortisol feedback clip, which can lead Teo. Um, a lot of the problems we see with adiposity and aging as well. We lose our autonomic nervous function. So our BP, our heart rate control and that can lead to things like falls. Um, our ability to respond to stress is much, much worse. This conveyed internal stressors such as immune challenges or temperature control or external stressors like falls or blood loss we just don't manage to cope with. It was a swell, Um, a lot of this leads to things like delirium, orthostatic, hypertension, constipation, all things that we're seeing more and more frequently. Noise. Um, it's like a rubber ball using its funds of it. Um, I want to go on until come by the pharmacokinetics and pharmacodynamics of aging. And I'm gonna do that night, and then we're going to take a break, um, for talking about it, um, sort of prescribing in the field elderly on what frailty is so pharmacogenetics. The effect of the body on the drug and then I mix the dog on the body are books affected by aging. If you think about our stomachs, they are slower to empty, so drugs will be at a lower pH for a lot longer, which will activate it. Some drugs on will will actually cause others to be less effective. Your muscle mass to your adipose tissue last changes, so you're more likely to have a bigger volume of fact than you are muscle mass. And this is going to change your volume of distribution for fat soluble meds, too, if you think about things even like, um, anesthetic agents were little anesthetic agents, you're gonna have a much bigger volume of distribution for those, which means they'll sleep into the tissues on the stay alone for a lot longer. Which is why often takes failure more elderly people longer to come running properly from anesthetic because the volume of distribution for those drugs are so much higher. Um, you know, it was much albumen generally in your bloodstream, which means that drugs that are carried buying the albumin are going to be increased. Lee freeze. You can have more of a free drug there, which may mean some drugs are again more likely to be running higher levels on Teo need lower doses. A lot of drugs are Have a first pass metabolism your liver doesn't metabolize. Eases efficiently on those drugs. Were kind around for longer when I was a nanny. Yes, a two. Um, I once had a 90 year old. None come in in SPT on I Waas told to give her. So the demos mean I have not done this before, but I was always told, When you're giving a tetanus in, don't bother with 3 mg, it never works. Go straight to the proper dose. So I very, really give this little numb 12 mg of adenosine on. I don't think she had a heartbeat promote 90 seconds because her ability to metabolize the dentist in with much less and she needed a much lower dose are kidney function doesn't work as well. So drugs that are clear green a ling we'll need to think about do suggest mint. This is really important for a lot of the drugs that we see all the time, such as thie new new wax. Such a. Some antibiotics, like taxes in which we do tend to use a lot. We need to be very thoughtful about renal function and not just easier. Far. We actually do think about creatinine clearance, which takes into account age sex of weight as well. So somebody in 92 who has a creatinine clearance off 30 has an e g f r. Sorry of 36. When you take into a client the fact that 45 kg and they're 90 to their creatinine clearance may well be much, much lower. More 15 16 on that really does affect what we need to think about prescribing. Um, receptors may be more or actually less sensitive to some drugs. Um, we need to think about that, especially things like Parkinson's. Describe it. I mean, we really also need to think about polio pharmacy on interactions of drugs. I'm gonna talk a lot about that later on tonight. I'm going to just be great for coffee, and I, um, on. Then I will going to talk about it more about prescribing in the field, elderly and frailty itself afterwards. If there's any questions I am happy to take them because I am aware. I have talked a lot for the last 20 minutes on I've covered a lot of ground. Thanks. Thanks for about generally, um, no questions. Problems at the moment. So why don't we go for coffee? It's almost for a possible Should we say with me? Not a bad time. I was well, so she would take 20 minutes for coffee. Um, on start back then at 25 too. Um, So you have to come back on that play five to your coughing. Thank you.