Drugs for Hyperlipidemia

foreign what's up Ninja nerds in this video today we're going to be talking about lipid lowering medications lots of cooled meds to talk about if we if you guys do like this video If it makes sense you actually do enjoy it you learn a lot please support us by hitting that like button comment down the comment section and please subscribe also you guys want some amazing notes some illustrations that our Ninja new team have put together go down the description box below we have a link to our website you guys can check that out all

right so please do that all right let's get into talking about this so with lipit alluring medications we're treating hyperlipidemia as the whole process right and patients who have hyperlipidemia the basic problem with this disease is that they have very high LDL levels okay and we'll talk about all these molecules they also will have high triglyceride levels or they may have low HDL levels that's the basic concept of a patient who has hyperlipidemia if you guys want to know a little bit about these more in detail lipoprotein metabolism go check out that video in our

biochemistry playlist it's it's lipoprotein metabolism we go in way more detail we're going to kind of simplify it here so the basic concept of hyperlipidemia we have to understand the physiology first of lipoprotein metabolism so here's going to be the intestines right so this is going to be a part of your intestines like a part of your small intestines really this is where we have absorption absorption of a lot of different things so when we talk about this we have a lot of different molecules so one of the molecules that we actually absorb across the

GI tract that are important in lipid physiology is cholesterol the other one is going to be free fatty acids this is how we really get triglycerides across and then we need something in order to be able to get the cholesterol the free fatty acids across the actual gastrointestinal tract we need a very special molecule and that molecule is going to be called bile acids or bile salts so bile acids these are really essential because what they do is the bile acids actually bind onto the cholesterol they bind onto phospholipids and free fatty acids they foregrounded

like this coating that enable it to be absorbed across the GI wall and into the lymphatic system right and so whenever these actually go across they go in the form of these things called me cells and the missiles would get taken up into the enterocyte they'll be metabolized and put into the lymphatic system so here's going to be our lymphatic system now once we actually put this molecule containing so we're going to draw like a little vesicle or a little like structure here this molecule right here is going to contain a lot of different like

lipoproteins on its surface but it's carrying lots and lots of cholesterol lots and lots of triglycerides this molecule that's carrying lots of triglycerides and cholesterol via the lymphatic system that will get pushed off into your circulatory system this molecule here is called a kylo micron and chylomicrons have high amounts of triglycerides and they also have high amounts of cholesterol tons and tons of triglycerides they carry whenever these molecules cholesterol free fatty acids bile acids the bile acids are really helping to absorb the cholesterol and the triglycerides into the lymphatic system they get into the lymphatic

system and then they move into the actual circulation right via the thoracic duct once the chylomicrons are here inside of our actual circulatory system it'll move via the circulatory system and then it'll actually come into areas of extra hepatic tissue so this is going to be extra hepatic tissue so tissue that is not the liver and what's going to happen here at this extra hepatic tissue we're going to have adipose tissue and skeletal muscle tissue there's the special enzymes that are present on the endothelial surface and this enzyme here is called lipo protein lipase and

what lipoprotein lipase will do is here's our chylomicron here's our kylo Micron moving through the circulatory system what the lipoprotein lipase will do is it'll actually take and break down the triglycerides that are present in this chylomicron and release them so it'll take a lot of the triglycerides here right out and it'll break them down into what's called free fatty acids it'll break them down into free fatty acids and that can be taken up into the skeletal muscle cells be utilized for ATP or it can be taken up into the adipose tissue and be converted

back into triglycerides but either way that's how we help to remove triglycerides from the chylomicrons Via this enzyme lipoprotein lipase remember that now once that happens this molecule this chylomicron that actually relieved tons of triglycerides to get taken up into the extrapatic tissue is now called something else so it's got less of the triglycerides this is called a kylo Micron remnant this is called a kylo micron Remnant and again it doesn't have as much triglycerides but it does have a lot of cholesterol what it'll do is it'll bind onto these receptors that are present on

liver and it'll take this actual cholesterol triglycerides and put this into the liver okay it'll take up the actual triglycerides and cholesterol from this chylomicron and put it into the liver now something really interesting in the liver can happen the liver actually takes lots of different molecules we'll go into this pathway a lot more later but it uses things like acetyl COA acetyl COA and from the acetyl-coa it'll actually be utilized to make something called cholesterol we'll go into this pathway more a little bit later but it's utilized to make cholesterol now we know that

cholesterol can be utilized in many different things to make steroid hormones to make bile acids and it can also be utilized to be able to make lipoproteins one of the interesting things here is that triglycerides can actually be combined with the cholesterol and when they're combined with the actual cholesterol these two molecules here combine together just like a chylomicron and the liver actually excretes this molecule out into the actual bloodstream and this molecule here is called a vldl it's got lots and lots of triglycerides and it's got a lot of cholesterol but a lot of

triglycerides just like a chylomicron it's just this is made by the liver now the vldl will actually move via your circulation your systemic circulation when it moves via the systemic circulation it encounters another enzyme in your capillary system near the what near the extra hepatic tissues such as the adipose tissue and the skeletal muscle tissue and what happens is at these tissues there is that special enzyme the lipoprotein lipase when this enzyme is activated what it'll do is it'll take the vldl molecules and it'll rip out what it'll rip out tons of triglycerides and take

and convert those triglycerides into free fatty acids that'll get taken up to the adipose tissue and stored as what it'll be stored as triglycerides or it can be taken up into the skeletal muscles and utilized to generate ATP but the whole concept is that we're taking the vldl up and removing lots of triglycerides once that happens it then gets converted into another molecule and this molecule is called a IDL then in IDL well then eventually it'll actually relieve a couple more structures and actually becomes something called a LDL So eventually it'll become a LDL now

LDL is really interesting it's a lipoprotein that has lots and lots of cholesterol but not as much triglycerides so so far you've noticed a trend that vldls and chylomicrons those carry lots and lots of triglycerides not as much cholesterol so in patients who are going to have lots of these chylomicrons or lots of these vldls circulating around they're probably going to have lots of triglycerides within their bloodstream patients who have lots of LDL carry a lot of cholesterol within their bloodstream as a particular problem now this LDL is really interesting and one of the problems

with this LDL is that LDL loves to bind onto a lot of receptors that are present in extra hepatic tissues one is the gonads the adrenal cortex y why would LDL be important here carries a lot of cholesterol guess what this cholesterol can be used for to make things like steroids steroid hormones so the gonads can use this to make things like estrogen progesterone testosterone the adrenal cortex can use this to make things like aldosterone things like cortisol things like gonadocorticoids you get the point the LDL will actually take and give some of that cholesterol

within its structure to these extra hepatic tissue to make steroid hormones that's the benefit but what's the bad side the bad side of LDL is that it also can go to other extra hepatic tissues you know in our blood vessels in the intimal lining okay and the sub intimal lining there's lots and lots and lots of these things called macrophages and macrophages love to bind to ldm molecules so they have on their surface they have lots of these things called LDL receptors they have like these different types of receptors and what happens is when the

LDL will bind with these receptors on the macrophages so here's all the LDL molecules it'll get taken up and when it gets taken up into these macrophages which happen to kind of situate themselves in the actual blood vessel wall when it gets taken off it takes up all this LDL and becomes filled and filled and filled with the actual flat fat globules and then this macrophage gets converted into something called a foam cell and then what happens is this really starts to accumulate a lot and a lot within the blood vessel walls and so this

can lead to a lot of fatty plaques that develop within the vessel walls a lot of fatty plaques that actually start to develop within the vessel walls and a problem with this is that it can really increase the risk of what's called atherosclerotic cardiovascular disease that's one of the most dangerous components of this but you get the point so LDL whenever there's lots and lots of LDL there can be lots of cholesterol to go to these extra hepatic organs and be utilized to make steroid hormones but it also can be utilized by foam cells make

these fatty plaques within the vessel walls now once the LDL has been done with its job what happens is the LDL will not only do this but it'll take some of its LDL particles and go back to the liver and on the liver you have these things called LDL receptors which will take the LDL up and really utilize and reutilize that cholesterol to make more vldls to make more other molecules like cell membrane components bile acids all of those things we're recycling the cholesterol so that's one way that we can remove the LDL now there's

one more protein here we've talked about triglycerides really with the vldls and the chylomicrons we talked about the ldls what about the HDL where the heck is that one htls are also really cool they're made by the liver and so they not only are they made by the liver but they actually are made by they're actually there's something called an HDL pool so some other molecules like chylomicrons and vldls and idls they give a lot of proteins that help to make something called this HDL structure but the liver definitely plays a big role in this

and so the liver will actually make something called an HDL molecule so it'll make this HDL molecule hdls are interesting They Don't Really carry any cholesterol when they're first synthesized so let's actually draw that there's really nothing in this they're really just it's really just a protein so this is a protein structure what happens with the HDL is it'll actually go to the blood vessel wall so let's say here's a blood vessel wall I'll draw another blood vessel it'll go to this blood vessel that has lots of fatty plaques within it and it'll go near

those foam cells that are in this fatty plaque wall and yank and rip some of the cholesterol and the fat out of the blood vessel wall so this HDL which is empty will move through this circulatory area pull some of the actual fat and cholesterol out of this and now this HDL molecule help to remove some of the plaque so now what did it carry within it now it's carrying with some of the cholesterol and the fats isn't that a cool concept so HDL is really good at being able to do what in this situation

pull some of the plaques from the actual blood vessel walls so that's the HDL so it's going to be carrying with it cholesterol and fat molecules and then what it's going to do is it's going to take this to the liver and on the liver there's also going to be these different different receptors that bind to the HDL and take the HDL back up and utilize some of that cholesterol that it pulled away from the vessel wall to make more lipoprotein molecules to make more types of cell membrane components make bile acids Etc so if

you kind of think about this when a patient has hyperlipidemia the disease process that really comes out of this is that if you have low HDL you have an increased risk of not being able to remove as many of these plaques from The Vessel wall if the patient has high amounts of LDL you have lots of fatty plaques that can be potentially formed and in patients who have high triglycerides again triglycerides are also deposited into the fat walls if patients have lots and lots of vldls lots and lots of chylomicrons again that also can play

a role into these fatty plaque formations as well as other organ dysfunction that we'll talk about so in this concept here this is really where we have hyperlipidemia now the question that you probably have is what is the the actual downside what's the negativity what's the problematic issue with having high LDL high triglycerides low HDL well we know one of them is the fatty plaque development within the vessel walls but you know you can also have deposition into solid organs what would that look like let's talk about that now all right so if a patient

has lots of ldls or lots of you know cholesterol triglyceride deposition into the vessel wall again they have lots of triglycerides lots of that can get deposited into the vessel wall or into solid organs less HDL to pull some of the triglycerides and cholesterol from The Vessel walls some of these as well as some of these solid organs what's the downside of that well if we start depositing this into some of the actual tissue in the actual skin this can lead to these things called xanthomas so you can see these things called xanthoma as you

can see other things particularly um sometimes you can actually see a lot of these skin findings sometimes around depending upon particular areas around like tenderness areas so you're going to see a lot of xanthomas another thing that you could see is you can can see a lot of plaque deposits around the medial portion of the eye lots of fat deposit around there and that's called xanthelasma so you can see something called xantha plasma a lot of fat deposits really that you can see not just here and the actual skin and around joints but you can

see this around the medial portion of the eye you can also see a lot of fat deposition around the cornea and they call this a corneal arcus this is a corneal arcus corneal Arcus the other thing is you can see lots and lots of fat deposition into the liver and then this can actually lead to like non-alcoholic fatty liver disease or hepatic steatosis and this can actually be a pretty nasty disease as well if you have lots and lots of this fat deposition so watch out for other things called a paddock hepatic steatosis and then

the last thing is whenever patients have extremely extremely high triglycerides this can really wreak a lot of havoc on the actual pancreas and it can lead to something called pancreatitis so watch out for pancreatitis seen with extremely high triglyceride levels usually as we're starting to see like greater than 500 or a thousand milligrams per deal we start seeing a higher risk of hyperlipidemia induced pancreatitis concept here so if a patient has high LDL high triglycerides and low HDL this could be some of the actual clinical features that we could see the other one which I

think is the actual more fearful one in the actual dangerous life-threatening types is that if we get a lot of these plaques within the vessel wall so if you have lots of triglycerides that are getting deposited here if you have high amounts of LDL you're depositing lots of cholesterol and triglycerides into here and if you have low HDL you're not pulling as much of the plaque and fat into some of the cholesterol triglycerides away from the actual vessel wall so you increase the risk of these fatty plaques and again this can lead to something called

atherosclerotic cardiovascular disease so if I start plaquing up these vessel walls that can really lead to a lot of problems especially perfusion past that kind of plaque area so generally this is going to reduce the blood flow around this area so imagine if this blood vessel is actually supposed to be delivering oxygen to parts of the brain what's going to happen now you're not going to begin delivering oxygen to what to the tissues of the brain and so you can start seeing things like Strokes so watch out now because now the patient has an increased

risk of something called a TIA they have an increased risk of a CVA so these are some nasty nasty things that you could potentially see the thing is if it's not perfusing The myocardium of the heart so now I'm not getting enough oxygen supply to The myocardium of the heart this can start to die what is this called this can lead to things like an end stemi this can lead to things like a stemi or this can lead to just your basic kind of coronary artery disease so your angina whether it be a stable angina

unstable engine Etc but you'll see a form of coronary artery diseases of another complication the other thing is if I've worn plaques and I don't Supply blood to the actual tissues of the lower extremities because they have plaques Within These vessel walls then I can start having like these cold non-well perfused extremities with lots of lots of claudication during exertional exercises and this could be something called peripheral artery disease with a very high risk of an acute limb ischemia so these are some really big things that you need to be able to recognize and realize

is a very potential complication from this disease now the last thing that you really want to be asking is what in the world increases LDL what's the thing that increases triglyceride what causes a decrease in HDL the basic reason of why this got this stuff happens is really beyond the scope of this lecture that's more of the pathophysiology but this could be genetic so this could be due to some type of familial type of process here or it could be acquired it could be due to certain disease processes like diabetes like hypothyroidism like nephrotic syndrome

medications weight increasing in weight obesity all of these things dietary changes so it's important to realize that there's a lot of things that can do this but what we need to figure out is how do I change this so my goal is to figure out a lipid lowering medication strategy that can work to either decrease my LDL decrease my triglycerides and increase my HDL so I have a lot of different lipid lowering medications that are going to work in this process to help me with that and the ones that we're going to go through step

by step here are going to be the HMG COA reductase Inhibitors this is the primary one and they're really good at dropping your LDL niacin really good at dropping the LDL but really really good at increasing your HDL and a little bit of the triglycerides it can decrease them fibrates they drop your trigs really really well and they have a little bit of an effect on again increasing your HDL bile acids to questions and cholesterol absorption numbers they're really good at dropping your LDL and then pcsk9 Inhibitors super expensive but they're really really good at

dropping LDL so we'll talk about a lot of these drugs in detail some of their adverse effects and then we'll go through how do we have a very straightforward guideline approach by the ACC aha guidelines of how we should treat a patient who has hyperlipidemia they have high LDL they have high triglycerides and low HDL and my goal is to do this how do I do that what's the therapy what's the particular patient population that I need to be aware of and go through that in a lot of details let's get to it all right

my friend so we're going to go through each particular drug we've built a foundation now we know how the lipoprotein metabolism Works we're going to kind of take parts of that diagram and focus on how some of these drugs work in particular areas right so we'll kind of keep going back to it talking about mechanism of action tying it to the pathophysiology what I really want you to understand all of these drugs will have an effect on at some point any of those three parameters the triglycerides the HDL the LDL that is the case yes

what I really want us to focus on primarily with each one of these drugs is what is the primary one or two of them that it really really focuses and fixes and patients who have hyperlipidemia okay so we're going to go over the mechanism of action and then which one of those three triglycerides HDL does it primarily affect is there something else we should know okay statins is the HMG COA reductase inhibitor category so this is going to be my friends this is that terminology that you probably heard the statins and there is a lot

of drugs in this category what I want to do is I want to actually break it into two parts one is called high intensity statins and the other one is called your moderate intensity statins I'm not going to go over all the dosages I don't think it's really necessary I'm going to go over two drugs that and that's the only ones I'll really talk about dosages for So within this drug category the first one that I'm going to talk about I'm going to use this up Arrow this or let's put high intensity high intensity statins

and there's really only two drugs that I want you to know here okay one is called rosuvastatin okay rasuvastatin and this drug if the patient is taking 20 plus milligrams of versuvastatin a day so I'm going to put 20 plus milligrams that is a high intensity Statin if they are taking atorvastatin atorvastatin and they are taking 40 plus milligrams per day of atorvastatin that is a high intensity Statin you'll you'll see later why I'm differentiating these these Concepts the next one is going to be your moderate intensity statins your moderate intensity statins now a receiver

Statin and atorvastatin are in part of that category but it's lower dosages okay so this would be rasuvastatin and guess what it just has to be less than 20 milligrams just less than 20 milligrams if it's going to be atorvastatin it's going to be less than 40 milligrams not hard right not hard to imagine now the other drugs that I want you guys to think about that are a part of this category one is called Lovastatin so one is called Lovastatin the other one is called fluvastatin another one is called Simvastatin and then the last

one that I want you guys to think about is called Pravastatin pravastatin okay but you get the point I really think the easiest thing to think about here is that these are the statins you see that name you know that it's one of these drug categories okay and then you'll know another mechanism of action in a section second but the big thing is really understanding because we'll talk about this when we get into the treatment guidelines the differences between high intensity statins and moderate intensity statins okay so all of these are moderate intensity their dosages

are different okay I'm not going to go through all of that I don't think it's that important I really just want you to know that these are going to be likely the most commonly utilized drugs receivastatin and the torvastatin they're going to be the most common in this dosage range they're high intensity in this dosage range they're moderate intensity and then any of these drugs are considered a moderate intensity type of Statin okay that's enough of that what we now need to talk about is how do these drugs work what is their mechanism of action

it's actually really stinking cool so here we have an hepatocyte so I'm taking the liver cell and I'm zooming in on it okay so in this liver cell remember I told you I used this like basic kind of concept that acetyl COA was utilized to make cholesterol that is true but the process of how it does that is actually a little bit more intense so acetyl COA is actually going to be first worked and converted into something called mevolonate so it's converted into something called I'm sorry it's actually converted into what's called hmg-coa first apologize

so first it's converted into what's called HMG COA then HMG COA is converted into mevalonate and then mevolonate is converted into cholesterol now we already know that cholesterol can be combined with something like triglycerides right so if we for example if I wanted to make this into something called a vldl what would I need to combine with the cholesterol to make this I would have to add in some triglycerides and I could make vldl right that's one thing here's something else that's really interesting cholesterol acts as a modulator of LDL receptor synthesis so here on

the outside surface here is what's called an LDL receptor believe it or not the number of LDL receptors is dependent upon the amount of cholesterol that is present with inside of the cell so generally here for example on our DNA we maybe have a specific Gene let's say here's the specific Gene that makes the LDL receptor here we'll actually do this let's take this and just in this blue I'm going to put there's the LDL receptor Gene cholesterol will modulate this activity and if we take this Gene that makes LDL receptors and just go ahead

and transcribe it and make mRNA and then on this mRNA transcript whoops sorry there's going to be a particular coding there there's going to be a particular coating there that is going to be used to make the LDL receptor then what I'll do is I'll take that mRNA and I'll take it to the ribosomes and I'll translate it and then I'm going to translate from this a particular protein structure so here I'm going to translate from these ribosomes a particular protein and this particular protein that I'm going to synthesize is going to get taken up

by the Golgi and it's going to get packaged and put into a very specific component here of a vesicle so here I'm going to have this vesicle here and this vesicle is going to go and fuse with the actual cell membrane and pump up the LDL receptor pretty cool right all right cool here's where the actual statins come into play there's a special enzyme that works right here that converts HMG COA into mevalonate this enzyme is called HMG co-a or a doctase not too hard to think about there right what I'm going to do when

I give a Statin is a Statin is going to inhibit this enzyme I will no longer be able to take HMG COA and convert it into mevolani what happens to the level of mevolony now it goes down if I don't make as much mavalani I don't make as much cholesterol if I don't make as much cholesterol and complex that with triglycerides I don't make as much vldl and so therefore vldls carry what type of molecule again triglycerides and so what would I effectively maybe do to my triglyceride level I may drop my triglyceride level because

I'm not going to be carrying as many vldls in the blood but here's where it's really cool okay less cholesterol says to something to this LDL receptor says hey I'm hurting I need to bring in as many LDL molecules because they have lots of cholesterol I need to bring as many of those LDL molecules inside because I need more cholesterol I don't have enough of it right now that's what the actual cell thinks so here you have an LDL molecule out here and let's say that you have a lot of them here's a lot of

these LDL molecules sitting out here and you want to bring these in but I don't have enough receptors well guess what this low cholesterol stimulates this stink out of the transcription of this particular Gene that is actually containing the LDL receptor so that I enhance and I make more mRNA I make more of the LDL receptors I transport more of the LDL receptors onto the cell membrane now look at this look at this I'm gonna pump out tons and tons of LDL receptors all over this dang cell membrane if I increase the expression of LDL

receptors what am I going to take out of the bloodstream LDL I'm going to rip LDL out of the bloodstream and so the LDL levels are going to do what they're going to fall and so I'm going to significantly drop my LDL levels so you see how Stan's one of the best things for them is that they drop your LDL levels they have a minor ability to drop your triglycerides there's one more thing how this mechanism actually works I don't know there's no particular potential literature on this but there is some thought here that cholesterol

may also whenever there's decreased amounts May somehow increase the synthesis of HDL that whenever there's less cholesterol may increase the synthesis of HDL so that the HDL can go out pick up more cholesterol from the peripheral plaques and the vessel walls and other organs and bring it back to him bring it back to deliver so it can make more so it has more cholesterol there and so theoretically you may increase your HDL levels but again the mechanism of how it does this I there's no potential answer to that but it may increase your HDL but

here's what I really want you to think about with statins the big thing that I really want you to remember is that these are going to be your first line hyperlipidemia medication and the primary thing that they will be good at reducing is LDL so their main thing that they will reduce is LDL they will have a minor benefit at reducing things like triglycerides and a minor increase in HDL but this is the big thing that I really want us to focus on okay that's why I want us to focus on what's the primary thing

that it can affect but that's statins and these are going to be your first line medications now what's some of the adverse effects that you want to be careful of because a lot of drugs are metabolized and actually specifically since statins actually go through the liver so statins are really metabolized pretty decently through the actual liver there can be some degree of metabolism that's occurring here that can actually cause some degree of increased cellular usage that can increase the patient's lft so it may cause a minor little hepatotoxicity that you want to be careful of

so watch for any increase in lfts there's one more thing stands have also been shown that what they do is they deplete a very specific molecule present in the skeletal muscles and we see this in a lot of different statins especially especially simvastatin you may even see this with atorvastatin you don't see it as much with with fluvastatin and pravastatin and we'll talk about this but what we see with some of the statins is that they really deplete this molecule called coenzyme Q now you probably will know that coenzyme Q is actually important within the

electron transport chain it's an important component of the electron transport chain so whenever a patient with who has you know the skeletal muscle you're supposed to take and utilize oxygen right and that oxygen will get taken up utilized by the skeletal muscles and then pump out ATP to allow for muscle contraction we know these things but if you have less coenzyme Q you're not going to have as much activity by the electron transport chain and so this will end up inhibiting this process and so you'll have less ATP to be able to allow for the

muscles to contract and to perform regular functions and this can lead to myopathy so one of the things that you want to watch out for in this particular disease is that this can really cause an intense myopathy which can maybe presented in a couple different ways one is it may just be pain it may be weakness What's worst case scenario is that you actually get what's called rhabdo rhabdo myolysis this is the worst case scenario where sometimes this can actually be so bad that you want to watch out that the patient does have doesn't have

elevated levels of creatinine kinase because the creatinine kinase can actually be one of the enzymes that actually leaks out of these muscles when it's super injured so watch out for that another thing is that if the muscle gets injured enough it can actually leak out something called myoglobin myoglobin and myoglobin is really hurtful to the kidneys and if it gets stuck in the kidneys the kidneys actually can really develop a pretty nasty injury to to this from myoglobin so another thing is watch out because whenever a patient starts hurting their muscles they can leak CK

out but they can also leak out myoglobin and that can lead to an acute kidney injury so the things that you really want to be thoughtful of with utilizing statins is monitor the patient's lfts it can cause a little bit of a hepatitis not too bad though but the main thing is that it can actually cause myopathy by depleting coenzyme Q10 and this can lead to less energy utilization within the skeletal muscles which can lead to myopathy which can present maybe only as pain weakness tenderness of the muscles but if it gets really really bad

it can lead to full-on Rhabdomyolysis of the muscles where they pop open release things like CK myoglobin that can be somewhat painful and in actually at high risk of an acute kidney injury so be careful the ones that have less risk of rhabdomyolysis or myopathy is going to be pravastatin and fluvastatin so these ones have less of the myopathy risk so if a patient starts developing problems consider switching them over to one of the fluvastatin approved pravastatin because those have less of a myopathy risk all right that covers this drug category the hmg-coa reductase Inhibitors

or the statins we know their mechanism of action we know the different categories we know the names we know some of the adverse drug reactions and we know the profound effect that they'll have on the hyperlipidemia profile now let's go to the next category and that's going to be nice and our nicotinic acid all right so the next one is niacin this one's actually an interesting drug now one of the things I think that's important to remember we didn't actually go through this diagram a ton but within adipose tissue it obviously holds tons and tons

of something called triglycerides okay it holds tons and tons of triglycerides now triglycerides or we've kind of abbreviated them TG can be broken down into something called free fatty acids and there's a special enzyme that does do that and that enzyme we're going to put here in red is called hormone sensitive lipase and naturally what it does it stimulates this pathway okay so it'll stimulate the actual conversion of triglycerides into free fatty acids by the adipose tissue now what happens is this free fatty acids can then be pushed out into the circulation when they're pushed

out into the circulation they then can go to the liver so this is going to be a liver cell this is a parasite the free fatty acids are then taken up into the liver cell okay now once it's taken up into the liver cell your free fatty acids in the liver will then be converted back into triglycerides okay to be converted back into triglycerides why is that important well triglycerides if combined with cholesterol make what type of molecule vldl right so it's going to pump out a molecule called vldl so let's actually pump this one

out here so if it combines with what if it combines with the cholesterol the triglycerides and the cholesterol make a molecule called VL DL and then what we know is that vldl would can eventually be converted into IDL and then eventually into LDL okay that's the concept that we have here we know this thing now what also is really really interesting now is that if I give the drug niacin what niacin is going to do is niacin is going to work too inhibit hormone sensitive lipase if I inhibit hormone sensitive lipase I inhibit the conversion

of triglycerides into free fatty acids that means I make less free fatty acids that means less free fatty acids get pushed out into the circulation that means less of them get taken up into the liver make less triglycerides less triglycerides combined with less cholesterol and if I have less triglycerides and less cholesterol combine I lead to less vldls and if I have less vldl to remember what do vldls give up what do they release into the extra Paddock tissue triglycerides and so what am I technically going to lower with the blood I'm going to lower

triglycerides so I will lower triglycerides the other thing is that if I have less vldl what else do I lower I lower my LDL so I can lower triglycerides and if by virtue I have less VL deal that's being synthesized I'll have less LDL that'll be synthesized so I have less of the LDL to actually bind onto these different plaques within the actual vessel walls so so far what I'm noticing with niacin is it's able to drop the vldls which can drop your triglycerides and by virtue if you have less vldl you have less ldls

that you're going to make okay here's where it's really really interesting and profound really when you think about it we know that the liver makes that molecule called HDL right and what's really interesting about HDL is that HDL it can take right here so we took here this vessel here's this vessel and here it has a plaque within the vessel wall right there's a plaque within this vessel wall and what we know is is that HDL will actually try try to go to these plaque where these macrophages are these foam cells lots and lots of

foam remember lots and lots of cholesterol kind of held Within These macrophages and what it's going to try to do is it's going to try to pull and rip out some of the cholesterol out of these macrophages it does it because it binds onto these things like scavenger receptors I'm just going to put Sr so these are scavenger receptors what happens is the HDL will bind with the scavenger receptors and sometimes what can happen is the macrophage can do two things one is it can actually lead to the catabolism of these HDL molecules so generally

HCL is going to want to try to suck some of the cholesterol out of the macrophages so but sometimes what can happen is is we can actually catabolize these puppies so we can sometimes catabolize the HDL and what would that do to the effective amount of HDL within the bloodstream that would lower the HDL within the bloodstream that's one thing the second thing is if the HDL is successful and it rips some of the plaque out of that vessel wall so here's the HDL the HDL after I ripped some of the plaque maybe from The

Vessel wall then what it does is supposed to go to the liver it's supposed to go to the liver and bind onto the liver here's the HDL molecules and then B kind of re-uptake and then kind of sometimes recycled into the liver right so then from here they'll get taken up into the liver and what would that do to the amount of HDL within the bloodstream that would effectively lower the HDL levels within the bloodstream here's what niacin decides to do niacin says I'm going to go ahead and I'm going to inhibit the catabolism of

HDL at the scavenger receptors so I'm going to decrease the catabolism of HDL if I decrease the catabolism of HDL I'm going to allow for more of the HDL to be present within the bloodstream oh here's the other thing niacin does Niacin also inhibits the re-uptaker the kind of like utilization of the liver from hdls and so then what do I do I don't take up as much HDL and I keep more of the HDL within the bloodstream so I'm increasing my HDL molecules so really when you think about what niacin is actually doing here

what is niacin really doing niacin is pretty decent at being able to do what it's not your first line medication it's more of an add-on therapy and really the most profound effect that's really interesting here is that it can increase HDL by reducing its catabolism and by reducing its reuptake so that's one of the most profound and interesting concept here is it can increase your HDL it can increase your HDL molecules not many other drugs will be able to do that so it increases your HDL the other thing that it can do is it also

has the ability to decrease your vldl which will decrease your triglycerides so also drop your triglycerides and it also can drop your LDL it can also drop your LDL so there's three profound effects of this drug one is it can increase HDL they want otherwise it can drop your triglycerides and it also can drop your LDL you can drop your LDL so that's how niacin will be utilized in this situation and I want you to remember the primary one here which is going to be it can increase HDL but it also can drop your triglycerides

and drop your LDL now with niacin again it's not a first line it's usually an add-on so if a patient has like you know they're on a Statin right and they're utilizing it to lower the LDL and the LDL still isn't in goal you can consider niacin especially if you want to drop the triglycerides too and increase their HDL that might be a beneficial situation but what's the downside what's the actual adverse effects which is the problematic thing with niacin one is that in the proximal convoluted tubule within your kidneys there's a transporter called an

organic acid anion transporter and what it does is it takes a molecule called uric acid I'm going to use a u here uric acid and it excretes uric acid so that uric acid could end up into the urine so here would be uric acid we would want to increase the uric acid in the urine okay now with niacin niacin has the ability to inhibit this process it's a son of a gun isn't it niacin can inhibit that transporter now you can't excrete uric acid so uric acid doesn't end up in the urine so there's less

uric acid that ends up in the urine and more of the uric acid actually stays in the bloodstream if more of the uric acid is not actually being excreted and more of it stays into the bloodstream now we have what's called high uric acid in the blood and this is called hyperuricemia what is a risk factor if you have high uric acid what can that do that can deposit into the big old toe and increase the risk of gout so that is one potential problem out of this disease is that it can cause hyperuricemia we

can increase the risk of gout so I would not give that to a patient who already has gout niacin okay second thing with niacin is that niacin has also potentially been shown to inhibit the insulin release or maybe even cause insulin resistance in some way shape or form so now if I am not making insulin or if the insulin that's actually being released is not responding but you know your receptors aren't responding to the insulin that's a problem so let's say that there's less insulin or there's less insulin response generally what that's supposed to do

is take glucose and bring glucose into the actual cells but if I have less insulin or I have what less responsiveness of the insulin on the receptor I don't bring as much glucose into the cell and so what happens to the blood glucose levels they increase so another adverse effect with niacin is that it can actually cause hyper glycemia okay one more it happens to be the most interesting concept here you know there's a pathway here where you take a molecule called arachidonic acid and generally One path is you convert into leukotrians the other one

is you convert into prostaglandins well what niacin has been shown to do is niacin can actually stimulate the arachidonic acid Pathway to form lots and lots of these prostaglandin molecules and if you make lots and lots of these prostaglandin molecules what this does is this acts on your blood vessels in the skin and causes them to vasodilate and increase capillary permeability and what that can do is that can actually cause a lot of flushing of the skin and so one of the things that you want to watch out for here is that it can lead

to Flushing it also can activate some of the mast cells and lead to histamine release which can lead to puritis so watch out for any kind of flushing puritis types of Sensations as well that you can see potentially with niacin so with niacin the big things to think about is it inhibits hormone sensitive lipase which actually inhibits triglyceride free fatty acid breakdown less free fatty acids is taken up by the liver less of it can be utilized to make triglycerides in the liver less combines with cholesterol to drop the vldl if you have less VL

deals within the blood you don't have as much triglycerides within the blood so you drop your triglycerides also if you have less vldl you'd make less LDL so it drops your LDL within the blood and it inhibits the actual the scavenger receptor so inhibits the catabolism of HDL and it inhibits the re-uptake of HDL which increases HDL within the blood all of these things will be somewhat beneficial in a patient with hyperlipidemia not first line though watch out for hyperuricemia watch out for hyperglycemia and watch out for a lot of this problem with vasodilatory effects

such as flushing puritis a lot of the itching that you can see with that you can treat this with aspirin and ibuprofen so aspirin ibuprofen are are basically a part of the Cox enzyme process so if I gave a patient such as something like aspirin so I can actually prevent this I can treat this with aspirin or ibuprofen because they're going to inhibit the arachidonic acid pathway by inhibiting the Cox enzymes okay keep your mind clear all right now that we've talked about niacin let's move into the next drug category which is going to be

our fibrates all right so now fibrates fibrates are actually going to be two drug particular names that you want to remember here one of them is called fenofibrate so one is called phenofibrate it's actually not too bad right because that's kind of within the name of the drug class and the other one is called gem fibrosal gym fibrosal with these two drugs okay what is the basic kind of mechanism of action how are they working what are they doing it's actually really sinking cool so you know your liver we obviously know that it will take

things like acetyl-coa utilize that to make cholesterol and then if it takes the cholesterol combines it with triglycerides it makes something called vldl we know that's the main lipoprotein that's made by the liver okay now once this vldl which is made by the liver is going to be moving through the circulation we know it encounters a very special enzyme in the extra Paddock tissues so this could be in the skeletal muscle area this could be in the adipose tissue we're just happening to pick the adipose tissue in this particular example but you could have some

skeletal muscles here as well we know there's a special enzyme here called lipoprotein lipase and we know that what it does it takes the triglycerides from the vldl and from what other molecule good question so from the intestines you absorb a molecule here that carries a lot of triglycerides and a lot of cholesterol as well and this molecule is called that carries a lot of triglycerides and a lot of the trig cholesterol is called kylo microns I'm going to put chyl okay but this is going to be a kylo Micron this is coming from the

git so from the git they're going to absorb this chylomicron and again these both if you look at the vldl and the kylo we know that they carry tons and tons and tons of triglycerides they carry cholesterol but not as much as they do triglycerides now this enzyme when it's active what it does it takes from the VL deal we know the vldls will eventually get converted into IDL and then into LDL and we know the chylomicrons will eventually get converted into something called kylo Micron remnants right so we know these Concepts we already talked

about in the Fizz what we did say also is that from these molecules what we would do is we would rip from them what triglycerides then the triglycerides when acted on by the lipoprotein lipase does what converts it into free fatty acids which is taken up by the what adipose tissue so it takes it up as free fatty acids because the lipoprotein lipase is going to convert that into free fatty acids so all of these free fatty acids will get taken up into the adipose tissue the skeletal muscle tissue utilize to make more triglycerides so

we know that within this adipose tissue it'll take the free fatty acids and make triglycerides if it was in the skeletal muscle would use it for energy right concept there done LPL is utilized in this step here so what LPL does is we'll do with this red arrow or this red situation here LPL works here to stimulate this particular pathway that's what it does what if I had a drug that could really enhance the activity of this lipoprotein lipase and it just takes and sucks all the triglycerides away from the vld on the chylomicrons puts

it into adipose tissue or puts it into skeletal muscle to be utilized for energy because again just for the sake of it I want you to also understand that there is again some skeletal muscle out here that I can also utilize it so here could be some triglycerides that'll be taken up into the Atwell again it'd be free fatty acids take it up into the skeletal muscle and be burned to make ATP so we could utilize it in those two ways what if I had a drug that could enhance the activity of the lipoprotein lipase

wouldn't that be cool guess what the fire breeds do that's what they do my friends so fibrates are pretty darn cool that they basically work to enhance or stimulate the activity of the lipoprotein lipase and so that stimulates the actually breaking down of triglycerides so that we're taking a lot more of these triglycerides and breaking it down into free fatty acid to be taken up into the adipose tissue or into the skeletal muscles so what happens to the total level of triglycerides within the bloodstream that's what I want you guys to think about what happens

this triglyceride level is going to plummet so the triglyceride levels are going to plummet so that's why this drug fibrates are in the absolute best at dropping the patient's triglyceride levels Now by virtue if you drop their amount If You Yank as you actually convert a lot of their vldls and break them a lot down you could also drop the patient's LDL right so you may also see that as well there's one more mechanism that's really cool though what it fibrates they love to stimulate the liver and they love to tell the liver hey libba

a level I need you to make lots and lots of HDL so one of the other cool Concepts here is that this fibrates also will increase the production of HDL so fibroids have the ability to also stimulate the liver to increase the synthesis of HDL so what I really want you to understand with fibrates is if I were to kind of highlight what they're really really doing with their mechanism of action because we already know that when we talked about the statins they really dropped the LDL that was the primary mechanism niacin it drops triglycerides

it drops LDL but the biggest thing is that it really increases HDL with the fibrates what are the two things that it's really doing it's increasing HDL and it's decreasing triglycerides that's the big thing here so it's increasing HDL and it's also decreasing triglycerides so it's similar if you think about it to niacin it's similar if you think about it to niacin because niacin also increases the patient's HDL and it also dropped the patient's triglycerides because what did it do it decreased the synthetic it decreased the amount of vldl because then the liver didn't have

as much triglycerides to bind with the cholesterol to make vldl so niacin and fibrates if you think about it acts similarly that they both increase HDL and drop triglycerides but which one's better at dropping triglycerides fibroids are going to be better at dropping triglycerides than niacin but both of these will help too decrease LDL increase HDL and increase triglycerides but which one's better dropping triglycerides again the fibration comparison to niacin all right that's a pretty cool concept there of how these drugs actually work what's the downside well one of the downsides is is if you

have a patient who's on a Statin so if you have a patient who's on a Statin and they're on a fibrate the downside is that the muscles will not be a very big fan of you the reason why statins are basically going to be taken and metabolized by the cytochrome p450 system right that's how they work to get metabolized via the cytochrome p450 system if you give a fibrate what a fibrate does is it works as a kind of a cyp450 inhibitor and it's going to inhibit the actual cytochrome p450 system from breaking down Statin

to the inactive metabolite and so what essentially happens is is you increase the amount of Statin now okay and if a patient is having myopathy as it is now you're going to have a higher Statin level and what that's going to do is it's going to deplete the amount of coenzyme Q so the Coq is going to Boop and what's this going to lead to this is going to lead to myopathy worsening myopathy so watch out for these patients to have worsening myopathy with a Statin and a fibrate combo so if a patient is on

a Statin and they're also taking a fibrate watch out for myopathy as well as watch out for maybe a slight bump in the lfts this may also increase the lfts a little bit as well okay so another potential adverse effect here is slight transaminitis but primarily myopathy there's one more okay so with hmg-core reductase this was increased lft's myopathy with niacin it was the flushing puritis due to the vasodilatory from increased prostaglandins hyperuricemia and hyperglycemia with fibrates it's concomitant use with statins increased myopathy increases LTS so it's just basically Statin adrs but one more gallstones

you're like what the gallstones fibrates are really interesting so there's an enzyme that's involved in making something called bile acid so we have this molecule called bile acids and then another thing that's a part of bile so bile is actually made up of two primary things one is cholesterol and the other one here is going to be bile acids so you'll have things like cholesterol and bile acids and phospholipids these are the big big components though of bile so this is really what kind of makes bile okay now when I give a fibrate what a

fibrate does is there's a special enzyme that's involved in the bile acid synthesis okay and this enzyme is going to be inhibited so what fibrates do is they inhibit this particular enzyme and what is this enzyme here's this enzyme that is important here this is called seven Alpha hydroxylase I'm going to kind of abbreviate here what fibrate does is it inhibits the seven Alpha hydroxylase this is inhibited so now the synthesis of bile acids is going to decrease if I have less bile acids now I'm going to have relatively relative more cholesterol this imbalance between

less bile acids and high cholesterol leads to a supersaturation kind of event and precipitation of what gallstones and this can increase the risk of cholelithiasis so watch out that fibrates be very careful and cautious that these patients may have an increasing risk of cholelithiasis because it inhibits the seven Alpha hydroxylase which is an enzyme involved in bile acid synthesis if you have less bile acids and a relative increase in cholesterol the combination or the ratio here that's important in bile production will lead to an increased risk of gallstones which can be sometimes problematic and increase

the risk of cholecystitis or cholidocolithiasis so watch out for that all right so that is our fibers we now know the drug Two drugs we know the mechanism of action here we know what's the primary effect that they're going to do on the lipid profile and we know the adverse drug reactions let's move on to the next category which is the bile acidity questions all right Bob asks these questions these are pretty interesting drugs so there's a couple of them one is going to be what's called cholesteramine cholesterolamine another one is called callistopal and then

there's another one called coal sevelem now these drugs are relatively interesting now one of the things about bile acids equestrants is that again they're not first line obviously statins are the first line but what they do is really really cool so if we go back to the git so here was where we're at the git within the intestines right I told you that there was three particular molecules that were involved here one is we had something like cholesterol so we had well the first one was bile acids we actually did that one green so let's

actually write that one down here so we have but actually we'll put it here so there's going to be bile acids which were combined with what else what else were they combined with they were also combined with free fatty acids and they were also combined with cholesterol and the whole concept is that these would be absorbed and when they were absorbed again bile acids would basically facilitate the absorption of cholesterol and free fatty acids which would help to make a particular molecule called chylomicrons and then chylomicrons would eventually get into the bloodstream right that's what

we know bile acids don't necessarily they don't actually get absorbed with this process they just are Incorporated because remember cholesterol and free fatty acid in order for them to be able to get to the actual intestine parasite and to get absorbed they need to be combined with bile acids to allow for them to be better absorbed into the intestinal fluid so bile acids help to make those molecules called me cells which helps in Aid and fat absorption but what's really interesting in bile acids is that these are negatively charged molecules so what I'm going to

do is I'm going to give a drug I'm going to give a drug because naturally what happens is bile acids after they're they're done helping with fat absorption to make chylomicrons and to get cholesterol and triglycerides into the bloodstream what they're supposed to do is they naturally are absorbed okay into What's called the entero hepatic circulation the enteropathic circulation this is basically a circulation where from the intestines the bile acids are taken up and then brought to the liver so this is going to be the liver and then from the liver what we know is

that the liver is going to be taking molecules like cholesterol right it takes molecules like cholesterol and then synthesizes things like bile acids we also know that it does a lot of other things with the cholesterol not only does it make bile acids and make things that are important with the cell membrane it makes things like vldl we know that whole concept but bile acids are generally really interesting in that there's one thing that we can do is that we can relatively recycle these and then if we recycle these what we'll do with these bile

acids is that will put them back into the biliary circulation so we'll put this into the bile so here's the biliary circulation so this is going to be a part of our bile and then from here we'll put them back into the intestine so there's just this kind of continuous cycle with bile acids that they're made by the liver they're put into the git they're helpful in absorbing fat molecules such as cholesterol and fatty free fatty acids into the actual lymphatic system and then eventually they get into the circulation after bile acids are done helping

with fat absorption as they get to the distal part of the small intestine they get reabsorbed when they get reabsorbed they go back via the blood to the liver via the enteropathic circulation and get taken up by the liver and then again from there they go back into the bile so it's just a nice nice recycling of this this molecule what if I gave a drug that didn't allow for that process so what I'm going to do is I'm going to I'm going to give another drug I'm going to give them a bile acid sequesterant

and this bile acids the question is extremely positively charged so it's a cationic molecule and what it does is it binds onto the bile acids and when it binds onto the bile acids the bile is then going to be lost in the poo poo so then what I'm going to do is I'm going to excrete the bile acids into the feces so now these bile acids are gone so my bile acids are going to be bound to this bile acid sequestrant and they're going to be lost into the poop so now what that does is

that leads to less bile acids that are actually going to be reabsorbed into the enteropathic circulation so that means that what I'm going to do is I'm going to inhibit I'm going to bind these together they're going to be fused together and I'm going to poop it out so they're going to go into the feces then I have less of the bile acids that are actually going to be brought and recycled be the enteropathic circulation so now what happens to the amount of bile acids that are present in the enteropathic circulation if I bind these

up it drops so I have less bile acids in the blood that means less bile acids are brought here to the liver to be incorporated into the bile and then be reutilized so now I got a problem I'm not going to be able to absorb cholesterol and fat as well so the liver says oh dang it okay well I was diverting my cholesterol into utilizing this for other things such as vldl and such as making cell membranes and other lipoproteins well I guess I got to start taking this cholesterol and synthesizing more bile acids so

the cholesterol that we were utilizing to try to make more more bile acids guess what happens to it it diverts it away from other Pathways we'll talk about what those pathways are in a second but now cholesterol is going to have to go to make bile acids so that it can put more of that bile acids into the biliary circulation to absorb more fats because we're not recycling it right now we're pooping it out what happens to the level of the cholesterol now it's going to plummet I'm going to drop the level of cholesterol on

the liver because I'm using it to make bile acids do you guys remember that process that I told you that if we go back to the hepatocyte if we were to go back to the hepatocyte here and the hepatocyte what we were noticing is that whenever a patient had lower levels of cholesterol so they had low cholesterol what that did is is that stimulated DNA to RNA RNA II proteins and then what we did is we expressed a very specific type of protein on the cell membrane to make more of these proteins to pull more

of the specific molecule back into this cell so if there's less cholesterol because we're diverting it into making bile acids that's going to stimulate the DNA the genes that make LDL receptors that'll increase the RNA increase the proteins and increase the number of LDL receptors if I increase the number of LDL receptors all of these LDL molecules will be taken up into the liver and I'll effectively drop my LDL levels I'll drop the LDL levels so one of the concepts here is that low cholesterol That was supposed to be um you know it's all being

shunted into making bile acids what it's going to do is it's going to stimulate the formation of an increase in LDL receptors and by making all of these LDL receptors we're effectively going to lower the patient's LDL because we're going to pull more LDL into the actual hepatocytes and so less of them are going to be within the circulation isn't that stinking cool so one of the things that I really want you to remember about biosity questions is you bind onto them you poop them out you don't reabsorb them less of it is in therapeutic

circulation less if it's taken back up and deliver that means that now you have less of it to add into the bile that means that you won't absorb cholesterol and fat as well your liver says okay I'll divert my cholesterol away from something else into making more of you when I make more of you though now now I'm going to create that that feedback loop that tries to increase LDL receptors if you increase LDL receptors you pour more LDL into the hepatocytes why because ldls carry cholesterol if I pour more LDL in I have more

cholesterol to use to make bile salts and other different things so that's the cool concept behind this the other unfortunate side effect out of this and it's not well understood but in this process of making bile acids it may activate certain fatty acid enzymes that are important or certain enzymes that are important in fatty acid synthesis and so as a potential adverse effect here's something that we may see is an increase in triglycerides there may be an increase in triglyceride synthesis slightly and so one of the things that you also want to watch out for

this is actually a downside to this drug is it may slightly increase triglycerides so again two potential Concepts to understand here one bile acids they're bound to buy lots of questions that get pooped out less of it gets recycled that means less of it can get put into the bottle it means you'll have less cholesterol fat absorption cholesterol says okay I'll divert myself all into you and so I'll make a lot of you so as you start utilizing cholesterol to make more bile acids you deplete the cholesterol within the hepatocytes if there's less cholesterol they

stimulate the synthesis of LDL receptors if I make more LDL receptors I pull more LDL into the hepatocyte lowering the LDL levels because I want to take the cholesterol from LDL and make more cholesterol as a downside to this because a lot of the enzymes that are utilized to make bile acids they're also utilized to make triglycerides so triglycerides might also unfortunately bump as a result of this drug so to take away from this bile asks us to questions their basic effect on the lipid profile bile acid sequestrants their basic effect on the lipid profile

is to do what two things one is they will significantly drop the LDL and they will slightly increase the triglycerides which is a down thing that's a downside right so they'll drop the LDL and they'll increase the triglyceride so one of the adverse effects of this drug is unfortunately hypertriglyceridemia may actually bump the triglyceride so it might be something that you want to avoid and a patient who has hypertriglyceridemia so that's one of the downsides okay so we understand three of these drugs we understand their mechanism of action that they inhibit bile acid reabsorption doesn't

get recycled cholesterol has to divert to making more bile acids so it leads to an increase in LDL receptors drops your LDL but because some of the enzymes that are making bile acids are also involved in fatty acid synthesis it can make more trigolous rights what's the other adverse effects besides hypertriglyceridemia well not only is cholesterol and free fatty acids and being absorbed important with bile acids but guess what else whenever you're absorbing any kind of fat whether that be cholesterol whether that be free fatty acids or anything like that guess what else combines with

that vitamins a d e and K and in order for this process to occur for us to absorb fat and to absorb fat soluble vitamins what do I need to facilitate this process I need bile acids so bile acids are extremely important two facilitate this process if I bind them up and poop them out am I going to be able to absorb fat and fat soluble vitamins no so when I give a bile acid sequestrant so now I'm going to give a bowel acid sequesterant that is going to inhibit bile acids the bile acids will

no longer be able to enhance the absorption of fat and fat soluble vitamins so what happens to the absorption you decrease the absorption of fat and you decrease the absorption of fat soluble vitamins there's one more downside another downside to this is that there's two drugs that are also really important and unfortunately can interact with bile acid questions they're unfortunately interacting with bile acid sequestions so here's going to be the git and here's going to be the circulation there's two drugs one is called digoxin which is going to be a drug that we can utilize

in heart failure as well as an afib another one is called Warframe which is basically an anticoagulant and Order when these drugs are absorbed guess who interacts with them while asking some questions they can bind on to them if bile acid see questions bind onto them they will inhibit the absorption of digoxin inhibit the absorption of Warfarin if you have less digoxin in the blood that actually may lead to the patient not being as well rate controlled and not be able to treat their heart failure if you have less Warfarin within the blood not the

patient's a higher risk of clotting so this is the downside to these drugs you know what is actually kind of a positive a patients decides to take too much digoxin they try to overdose on it or they take too much and they forgot guess what they could take to potentially bind that up and actually act as a kind of an antidote you can give them colosterone cholesterol co-celem because they'll bind onto the digoxin help it to get pooped out so we now know the names of the drugs the mechanism of action their effect on the

lipid profile and the Adverse Events which is hypertriglyceridemia and decreased absorption of fat soluble vitamins and decreasing drug concentrations of digoxin and Warfarin within the bloodstream okay my friends let's now move on to the next one which is your cholesterol absorption Inhibitors all right my friends cholesterol absorption Inhibitors these are pretty cool drugs as well they're actually very commonly utilize that I actually say that this is one of those like second line medications that you can add on with the Statin it's pretty decent and I actually like sometimes if a patient can't tolerate like a

Statin this is actually the second line drug so that's a really important thing to be able to remember and there's two reasons for that one is that they've been they have very little adverse effects and they can profoundly drop your LDL so for these drugs there's really just one and that is acetamin a Zeta MIB and how do these drugs actually work it's actually pretty cool so from your git so here's your git right so through your intestines you're going to have those different molecules so we already talked about them one is that you'll take

cholesterol and you'll also combine this with free fatty acids if you wanted to you can add in there the vitamins a d e k and then you can also in the last molecule that's important in being able to help with the absorption of these molecules across the git and this is your bile acids we already talked about how the bile acids equations will bind onto these prevent their reabsorption inhibiting the bile acid recirculation process and then we talked about all that already we don't need to go over that anymore now here's where it's really cool

now cholesterol free fatty acids all these things are basically absorbed across the GI tract and eventually what happens is they they actually technically have to go through we know that they go via the chylomicrons so they go via the chylomicron so here we'll put like your lymphatic system they actually move into the lymphatic circulation first so let's actually just follow cholesterol we know that they go through the actual lymphatic circulation first then they get into the actual blood and eventually we know that they're going to go to the liver so we know that the chylomicrons

especially the remnants especially the rim here we'll put kylo micron remnants we know that these are going to take and bring the remaining amount of cholesterol and a little bit of triglycerides so kylo remnants to the liver okay they bring it to the liver and when they bring it into the liver they push the cholesterol in here okay now what we know is is that cholesterol is obviously very important to be able to make a lot of different things okay we obviously know that it can make bile acids we obviously know that it can make

vldl we obviously know that depending upon the amount of it it also controls the the expression of LDL receptors so with this particular drug here's what we're going to see when we give a cholesterol absorption inhibitor such as acetamib it's going to inhibit the absorption of cholesterol that means that the amount of cholesterol being carried by the chylomicrons is less so there's going to be less cholesterol present Within These chylomicrons that means less cholesterol will be taken into the liver oh my gosh do we already know this mechanism if there is less cholesterol present within

the liver okay what's the downside to that well I guess actually it's a good thing one is it's going to increase the expression of what kind of receptors it's going to increase the expression of LDL receptors and so if we increase the expression of LDL receptors what are we going to do then I'm going to increase my number of LDL receptors because again we already talked about this before the whole mechanism is that it actually does what low cholesterol stimulates the synthesis of DNA to RNA rna2 proteins proteins such as LDL receptors are then packaged

send up to the cell membrane so they can bind ldls bring more ldls in so the ldls that have lots of cholesterol can try to increase the cholesterol on the liver that's the whole concept so if I increase the number of LDL receptors what I'm going to do is I'm going to bind way more LDL molecules and I'm going to bring them into the liver and remove them from the blood so I'm going to drop the LDL molecules oh that's pretty cool so that's one concept the other thing is that if I have less cholesterol

less of this cholesterol combined with triglycerides so if I have triglycerides that are actually available here if I have triglycerides that are actually available here there's going to be less cholesterol to bind with the triglycerides so this will effectively drop the number of vldl molecules so this may drop the vldl as well and if you drop the VL DL you may slightly drop the triglycerides in this patient population but it's not going to be profound so this may drop the triglycerides but I think one of the biggest things to think about here is the profound

effect that it's going to have on the LDL so when we talk about this again how do these drugs really work is that a MIB it works too inhibit the absorption of cholesterol across the git into the lymphatic circulation meaning you're going to have less chylomicrons that get absorbed if I have less chylomicrons so these are chylomicrons kylo microns I'm going to have less chylomicrons then after they go through the circulation and then they interact with the again we know that it interacts with what type of protein in the circulation here we'll just draw for

completeness sake there's an enzyme here which is around the extra hepatic tissues the lipoprotein lipase after it then gets metabolized it's then going to contain less triglycerides and mainly just cholesterol this is a kylo Micron remnant they will then go to the liver less cholesterol is taken up into the liver then less cholesterol is available to be able to make vldls meaning a mild drop in triglycerides less cholesterol stimulates the synthesis of LDL receptors to pull more LDL out of the blood and into the liver and so it'll really drop the LDL so what type

of effect will cholesterol absorption Inhibitors primarily have on the actual lipid profile the primary effect that a zetamib will have on the actual lipid profile is that it will profoundly drop the patient's LDL that's really the big thing that I want you to remember here it'll profoundly drop the patient's LDL with a very minor drop in there triglycerides but the primary thing is going to drop the LDL so this is why this is actually one of the first line medications of a patient can't tolerate a Statin because it can actually drop the LDL pretty well

now one more thing to think about what are some of the adverse effects it actually is a very very mild effect on the lfts very mild very rare to actually have this at all to be honest with you so I'd actually I honestly remember that it's relatively rare but it's something we should mention and it also can cause a little bit of diarrhea but it's honestly not too bad it's very mild and not too common so with that being said this is a very well tolerated drug with very little adverse drug reactions which makes it

very appealing for these patient populations who have hyperlipidemia all right so pcsk9 Inhibitors these are actually really interesting proteins okay one of the drug names that didn't want to remember they're Sons of Guns there's like aloe rokumab and evolokumab now what you really want to remember about these particular drugs is how they actually work it's really really cool so here we have these molecules here what are these on the hepatocytes these are hepatocyte these are your LDL receptors now what's really cool is I'm going to draw this here like this like black circle here this

protein here is called the pcsk9 protein so what is this protein right here called This is called the pcsk 9 protein what happens with this PCS canine protein is it's kind of a signaling protein that really helps to take some of the LDL receptors and endocytose them to actually endocytose them so actually this will help with what's called endocytosis this is mediated via the pcsk9 protein once they're endocytosed they actually combine with something called lysosomes and lysosomes will actually fuse with this endosome and try to break down and degrade the LDL receptor so the lysosomes

will actually start eating up and then what they'll do is they'll degrade the LDL receptor and so the end effect there is that you have less LDL receptors that are present on the hepatocyte membrane to bind LDL and bring them into the actual cell what if I had a drug which I do a pcsk9 inhibitor will actually inhibit the PCS canine so what I'm going to do is I'm going to inhibit every single one of these proteins that are bound to the LDL receptor I'm going to inhibit the endocytosis because if these aren't functioning you

can't endocytose therefore I will not allow for any of this lysosome endosome fusion and I will decrease the degradation of LDL receptors and so then what happens in my number of LDL receptors that are present on the membrane I'm going to increase my number of LDL receptors that are present on the membrane so these are the drug category here so we'll just put the pcsk9 Inhibitors they inhibit this this actual protein thus the name and they excessively increase the number of LDL receptors they decrease the degradation so if you have a number of LDL receptors

that are normally this is a normal process your normal processes actually take and endocytose them degrade them and then help to make more but that means you have less of them available to binance the LDL if I use this drug I'll inhibit their endocytosis their degradation their recycling process and I'll keep more of them on the cell membrane so that means that I have more of these to bind onto LDL particles that are present outside of the hepatocyte and if they combine onto these LDL molecules now they can take more of the LDL molecules in

and so what are they going to do to the LDL levels then effectively so the LDL levels will be significantly reduced they'll be significantly reduced so that is the primary effect out of Allah rocomab and evalucumab the primary effect on the lipid profile is to reduce LDL significantly okay that is pretty much it there really isn't anything else that you guys should know for its effect it inhibits the PCS canine proteins which inhibits the endocytosis of the LDL receptors inhibits their degradation by lysosomes and keeps more of them on the cell membrane to poor pull

more LDL in that's the whole concept so if that happens that means what happens to the amount of LDL that is present within the bloodstream my friends the LDL within the bloodstream is going to and drop beautiful that is the basic concept that I want you guys to understand about this truck now with the respect to adverse drug reactions or effects it's very mild to be honest with you it may cause a little bit of myalgia and it may just cause a little bit of injection pain so a little bit of injection pain because it

is given subcutaneously so it's given subcutaneously so there may be a little bit of injection pain sometimes it may cause a very mild upper respiratory tract type of infection symptoms but for the most part the most common adverse drug reactions is myalgia and injection site pain that's really it so it's a very very good drug that has the ability to significantly decrease the patients LDL within the bloodstream okay that covers all of the categories of drugs we've covered the HMG Coe reduction Inhibitors we covered niacin we covered fibrates we covered bile acids questions we cover

cholesterol absorption Inhibitors and we finished off with pcsk9 Inhibitors we now know all of their mechanism of action we know what's their primary effect on the lipid profile we know their adverse drug reactions now the Latin we know their names what is the last thing that we should talk about a patient comes in they have hyperlipidemia whether it be due to high LDL low HDL high triglycerides how do we approach these patients what's the ways that I would know when to start lipid lowering agents which agents to start them on and when to add on

these other ones besides the Statin let's talk about it all right my friend so patient comes in they have some type of problem where you need to consider putting them on a lipid lowering agent when a patient comes in and they have any types of clinical atherosclerotic cardiovascular disease that is an indication to start them on some type of lipid lowering Med the most common one that you're going to put them on what's the first line I've already I said at the beginning of the video and I've said it throughout multiple processes that statins are

going to be your first line so we should focus our attention on statins here so patient comes in they have any type of clinical atherosclerotic cardiovascular disease what does that mean they suffer a stroke they suffer an MI they have peripheral artery disease any of these that are actually some type of event like that you start them on a Statin now with that being said if they suffered one of these events you have to think about the patient's age the older they are the more likely they are to experience side effects and that's the problem

especially myopathy so it's important to think about that is the patient greater than 75 years of age or are they less than 75 years of age at greater than 75 you probably don't want to be blasting these poor patients with high intensity statins so what I would say is for this patient population consider some type of moderate intensity Statin so this means that you can consider receiver Statin less than 20 milligrams atorvastatin less than 40 milligrams or Lovastatin fluvastatin simvastatin pravastatin okay just think about that and the reason why is the lot of the myopathic

effect all right and just the true benefit that they would gain being already above 75 years of age at this point if they're less than 75 you want to be aggressive you they they have a potential to live a lot longer and so because of that you don't want to play around and you want to put these patients on high intensity statins okay high intensity Statin so again at this situation you're putting one greater than 20 milligrams of receivastatin or greater than 40 milligrams of atorvastatin okay the next situation here is if the patient has

a whopping LDL that is greater than my gosh I could imagine this um greater than 190 milligrams per DL if that LDL is that high you have a very high risk of atherosclerotic cardiovascular disease okay because of that because your risk now you have a very high risk of high risk of atherosclerotic cardiovascular disease and many other complications here you really need to get on top of these patients you don't want to delay and so for these patients regardless of any other type of parameter you start them on high intensity statins high intensity Statin and

so this would be your receiver Statin greater than 20 milligrams or you're atorvastatin greater than 40 milligrams okay next category so this one's kind of a couple hitter here so we have a patient who has diabetes mellitus okay they also are 45 to 70 years of age so 45 to 70 years of age and then the last component here is you look at their atherosclerotic cardiovascular disease risks that's the third parameter that you add on here but that's going to lead to this dichotomy here so you take into consideration consideration a patient who's diabetic diabetes

definitely increases the risk of atherosclerotic cardiovascular disease right and hyperlipidemia it's really important because what it does it actually oxidizes LDL which increases a lot of those problematic plaques that you see Within These patients so diabetes is a very high risk factor for hyperlipidemia and it can lead to a lot of oxidized LDL particles which really can accelerate a lot of the plaque process and if a patient's like this age you really want to be careful with that so what you do is you rest stratify these patients into two categories and you look at their

atherosclerotic cardiovascular disease risk calculation so if you guys go into MD Cal can you put in their risk factor calculation their percentage based upon their atherosclerotic cardiovascular disease you're looking at a particular number what you want to know is is it greater than 7.5 percent or is it less than 7.5 percent if your risk is greater than 7.5 percent you're at high risk of a clinical atherosclerotic event so because of that you need to be on a high intensity Statin if your wrist is less than 7.5 you don't need to be as aggressive you're at

less risk of in a clinical event so for these patients you want to do high intensity Statin and then for this patient population you can relax a little bit and do a moderate intensity Statin the last category is you have a patient who is not diabetic but they are 45 to 70 years of age and again you're really just looking at this patient population and trying to figure out is this patient population are they greater than is there atherosclerotic cardiovascular disease so again for this one it's 45 and they have and atherosclerotic cardiovascular disease risk

greater than 7.5 percent if they do this patient will qualify for a moderate intensity Statin so let's recap this again patient comes in they have a clinical atherosclerotic cardiovascular disease event if they're greater than 75 you can do modern intensity if it's less than 75 moderate you can do high intensity if they're LDL is greater than 190 they're super high risk high intensity Statin if they have diabetes which now puts them at high risk for hyperlipidemia and atherosclerotic cardiovascular disease helps to cause excessive oxidation of LDL particles and really forms a lot of plaques these

patients are high risk determine their Risk by stratifying them and based upon their calculation is it less than 7.5 or greater than 7.5 if it's greater than 7.5 high intensity less moderate intensity and then the last one is a patient who doesn't have diabetes but their risk is greater than 7.5 percent for an event and they're 40 to 75 you do a moderate intensity Statin okay and that covers how we treat these patients so you can obviously see that the first drug that we talked about is going to be the drug of choice no matter

what we really want to think about is what if the patient is having an adverse drug reaction they can't tolerate their Statin and so we need an alternative then we can think about other drugs but I think the better thing is if a patient maybe is on a Statin and they're still not at goal you could add on another medication to have a combo therapy so it is important to realize yes if statins aren't working the next best choice could be one of the drugs that we talked about in these scenarios it could be things

like we talked about cholesterol absorption Inhibitors are really really good or maybe even something like you know your bile assets sequestions could be a potential option we'll go through all of these things but I think the easiest way to remember it is if you have to do a combo therapy or you can't do a Statin treat them based upon which parameter of the lipid Pro profile they improve so let's talk about that now all right so I want you to think about this in two ways combo therapy a patient who's on a Statin they're on

that Statin to be able to lower their LDL to increase their HDL to decrease their triglycerides we know that that drug can do all three effects right there may be on the Statin but they're still not at their goal so we still haven't gotten that LDL below the goal that we want and obviously the LDL goals Can Depend I mean generally optimally you want it to be LDL less than 100 would be a nice goal in HDL greater than 60 would be a nice goal so I think that's important to think about that if you

have a patient who's on a Statin and you've maximize that without reducing without causing a lot of adverse drug reactions and they're still not hitting that goal then what drugs would I add on well it depends that's why I talked about the lipid profile so intensely what if I have a patient who still has a high LDL so then I want to think about which drugs really lower the LDL which drugs really lower the triglycerides and which drugs really increase my HDL because if I'm not meeting my goal it might be good to know which

drugs actually approach that and add those drugs on accordingly so I want to know now okay I have a patient who's on a Statin but their LDL is not a goal their triglycerides are not goal and then they're also HDL is not at a goal that I would like which drugs could I add on that's a pretty cool concept now and so really with these the first thing that I want you to think about is two particular drug categories one is if they're on a Statin they're not responding to it or they're let's say that

they're not even on a Statin you could consider a pcsk 9 inhibitor this is a really good drug that drops your LDL the other one is the cholesterol absorption inhibitor would be another really good one called acetamib now if the patient fails a zetamin or they can't take a zatamib then you can add on two other drugs then this would be the bile acid sequestrants just be careful if they have hydroglyceridemia and then the other one would be niacin because niacin has somewhat of a decent effect on dropping LDL but it's not going to be

the absolute best so here is the patient who is on a Statin right so this patient is on some type of Statin and you want to know what else could I add on to the mix or maybe they did a Statin couldn't tolerate it what other drug would be another option so if I'm trying to drop LDL PCS pcsk9 Inhibitors is one option the other one is acetamip if they fail a zatamib so if they fail is that a MIB so it's actually put here with a negative sign here they fail is at a MIB

then you can go to bile acid sequestions or niacin as an option okay patient has triglycerides that are still high at goal with their Statin or they can't tolerate a Statin which drugs would be able to be added on here we already know which ones which ones drop them niacin and fibrates that's it niacin and fibrates are great at dropping the triglycerides and they're also good at dropping what else the next drug category so the ones that increase HDL because niacin inhibits what inhibits the hormone sensitive lipase so you don't break down triglycerides into free

fatty acids don't get utilized by the liver to make vldl so you have less vldls to be utilized to drop off triglycerides so drops triglycerides it also inhibits this uh macrophages from catabolizing HDL and decreases reuptake fibrates stimulate LDL simulate HDL synthesis but it also stimulates so you break down a lot of the triglycerides from the vldls and chylomicron so these are great which one's better which one's better at dropping triglycerides though five rates will be better okay then the next thing is HDL if a patient has super high HDL they're two drugs that would

actually do that is the same ones that drop the triglycerides so niacin and fibrates niacin and fibrates so these are the ones that I really want you guys to think about now the question that you may have is how do I know which one to pick it depends upon the patient's history and their adverse drug reactions if I have a patient who's triglycerides or HDL is not a goal and I got to figure out okay which one do I do niacin or fibrates if they have if a patient has some underlying leviasis already that might

not be a good idea to maybe do something like a fibroid I'd better be very careful with that if a patient has some type of already they're already on a Statin I better be careful with giving them a fibroid because they may actually increase their myopathy if a patient's on niacin I better be careful that if they have gout or if they have hyperglycemia with diabetes or also be careful that they have a lot of the reaction of the flushing and the puritis and the redness you get the point with pcsk9 Inhibitors they're very well

tolerated with his edamame is really well tolerated but if they fail this one or they can't tolerate this one then you get into these two drugs and then bile asks the questions you got to be careful it can increase your triglycerides can reduce the absorption of fat soluble vitamins it can block the digoxin and Warfarin absorption that's a problematic thing so thinking about the adverse drug reactions and the problematic issues that can come from that will help you to determine which is the best option here I hope this made sense if it didn't let's actually

do some practice problems to reinforce it alright guys so here we go which of the following is the most common adverse effect of antihyperlipidemic drug therapy interesting elevated BP GI disturbance neurologic problems heart palpitations I think none of them mentioned anything about an elevated blood pressure if anything it might actually lower their blood pressure gastroenter gastrointestinal disturbances yes there was some of them at risk of diarrhea some of them could have gi upset some of them can have hepatitis there's so yes I'd say gastrointestinal sure neurologic if anything it's actually going to decrease the risk

of kind of strokes and then heart palpitations no it'll actually probably likely decrease the risk of heart palpitation so again I I don't think any of these other than gastrointestinal disturbance would be the correct answer uh which of these drugs decrease cholesterol synthesis by inhibiting the three hydroxy 3-methylgluterol coenzyme a reductase another name for this enzyme is called HMG COA reductase so it's the same thing which one of these would do that it has to be a Statin an hmg-core reduction so it's C Lovastatin which of the following non-statin drugs lowers ldlc most effectively just

lowers LDL it's got to be the pcsk9 Inhibitors because they just massively decrease the amount of LDL receptor degradation and increase the LDL receptors and cause massive decrease in LDL so it has to be pcsk9 that was the kumabs so B which of the following drugs binds bile acid so it has to be a biosity question in the intestine thus preventing the return to the liver via the enterobatic circulation and if your member less bile acids cholesterol has got to make a lot of it less LDL receptors um so it actually increased the synthesis of

LDL receptors you pull more LDL into the actual liver cell but it also can increase those synthesis of triglycerides this was the bile acid sequestions which one is this cholesterolamine cholesterol or coal Sevilla so it's got to be C colosteramine 65 year old man has Type 2 diabetes and LDL of 165 which of the best which of the following is the best option to lower LDL and decrease the risk of atherosclerotic cardiovascular disease vents in this patient population so for this patient again what's the first line drug to decrease atherosclerotic cardiovascular disease it's statins they

didn't mention in here what's the category and which one's the high intensity moderate intensity all of those things but again if it was a 65 year old so that's 40 to 75 they have diabetes and let's see that their atherosclerotic cardiovascular disease risk was less than 7.5 percent you could go with a moderate intensity and if it was greater than 7.5 it would be a high intensity but in general it's going to be a Statin versus Statin okay next one 62 year old female with hyperlipidemia hypothyroidism is prescribed cholesteramine and levothyroxine what advice would you

give her to avoid the drug interaction between these two well again remember cold stermine can bind drugs the two most common ones is going to be digoxin Warfarin and the third one would be levothyroxine so it's better to just give the levothyroxine first have it actually start getting absorbed first and then give the coal steering so it doesn't bind it up and inhibit its absorption so I'd take the drug first leave with thyroxine and then the cold stermine later so take levothyroxine one hour before cold steering yes uh adverse effective niacin okay so here we

go 72 year old male um started on sustained release niacin two weeks ago he reports uncomfortable flushing and itchiness that he thinks is related to the niacin definitely the case which of the following can help manage the adverse effect of niacin therapy will remember niacin increases prostaglandin synthesis causing vasodilation causing Acres capillary permeability causing flushing redness and as well as causing pruritus via the histamine release if we give a drug that inhibits the prostaglandin synthesis via the cox-2 enzyme aspirin ibuprofen you would give that patient that now the question that they're trying to trick you

is would you give it before or after give it before because once you give the drug it's going to likely hit that pathway so if you give it before again aspirin is going to have no other effect other than just inhibiting the prostagland synthesis it's not going to alter all the other effects of niacin that it has on the lipid lowering effect so just give it before you give the niacin so that it can shut that down so that niacin won't hit that pathway so it would be before taking knives medicine hyperlipidemia and renal insufficiency

okay so 72 year old man with hyperlipidemia and renal insufficiency has been treated with a high intensity atorvastatin so greater than 40 milligrams for six months is LDL is 131 still not a gold triglycerides oh my gosh 710 and HDL 32 he's in big trouble his position wishes to add on another agent for hyperlipidemia which is the best option to address the hyperlipidemia in this patient so they have um and a high LDL and they have a heck of a triglycerides they're already on a Statin so this is the combo therapy which one of these

drugs has the ability to lower triglycerides well fenofibrate yes it lowers triglycerides pretty significantly niacin will drop triglycerides cholesterol um no it actually will increase triglycerides and gemfibrosyl a very mild shrub drop in cholesterol I mean triglycerides so really it's b or a now I told you which one's better fibrates will significantly drop your triglycerides niacin will also but fibrates are definitely going to be better your answer would be like oh it's vibrates there's one downside niacin is not as much ringly excreted as compared to fibrate so fibrates are extremely really excreted and so the

patient has renal insufficiency that would be a potential contraindication or a downside to giving fibrates that's one thing that you got to be careful for so because they have renal insufficiency I would not give them a fibroid and instead I would give them niacin so that is the only other caveat to this all right last question which patient population is most likely to experience myalgia or myopathy with the use of hmg-coa reductase Inhibitors well anything that increases the amount of hmg-coa reductase Inhibitors so if a patient's renal failure it's really excreted so yes they will

have higher levels of that drug which means that they'll deplete the coenzyme q and then definitely cause myopathy patients with gout that has nothing to do with it hypertricular nothing to do with it patients taking Warfare nothing to do with it so patients with renal insufficiency yes because you're going to not excrete as much of the statins into the actual urine and you're going to have more of it kind of just flooding your bloodstream and causing depletion of coenzyme Q so yes a all right my friends that covers the questions and the cases that covers

the actual lecture on lipid lowering medications I hope it made sense hope that you guys enjoyed it and as always until next time see you in insurance [Music]