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Lipid lowering drugs | Pharmacology | USMLE STEP 1

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Hello everyone today we will be discussing about lipid lowering drugs now these drugs are easy to understand but they are also easy to forget and they are extremely high for usmle step 1 so let’s try to understand it today and suppose this is our gi tract and lipid is absorbed in small intestine so let’s say cholesterol is being absorbed here okay and by lapse bile

Acid will be absorbed in the distal part of the small intestine now the easiest way to decrease the amount of cholesterol in the blood is to simply stop the absorption of cholesterol right here now the drug that does this is called acetamide it’s called is tmi now this is the easiest mechanism to lower the cholesterol there are no difficult mechanism involved no

Enzymes nothing it’s so easy to understand that’s why the name of the drug is easy t my try to understand it like this i try to remember it like this easy to my it means that is it is is this having the easiest mechanism like very simple mechanism to understand so that’s first mechanism by which we can lower the level of cholesterol in the blood another mechanism is

By simply stopping the reabsorption of bile acid if you stop the reabsorption of bile acid that means bile acid will not be able to go from small intestine into the lever and lever will try to produce more violent bile acid with the help of cholesterol so liver will start using the cholesterol now these this drug acetamide is stopping the absorption of cholesterol

And the drug that decreases the reabsorption of bile acid it is called bile acid resins so by acid resins now when when both of these drug works they they causes depletion of cholesterol and when liver needs more cholesterol try to take it from the blood in the form of ldl and this is the reason why as a team i’d and bile acid resins they decrease the level of ldl

So this was the simple mechanism of easy type and bile acid resins now let’s try to understand how which i’m in which protein the saami blocks so the name of the protein that is at ma as at m my blocks is called name and pick c one like one protein now these are not this is not a high thing but it is good to know that is that it might blocks niemann-pick c1 like

Root c but like one protein now how the bile is bile acid resins well let let’s try to understand that so bile acid resins they are positively charged sorry so by lassiter since they are positively charged while bile acids they are negatively charged so by lassiter since they are not absorbed in the small intestine but they combined with the bile acid resins i

Mean bile acid resins combined with bile acid in the small intestine and they form a complex which is not which can not be absorbed in the small intestine so it is unobservable and it is excreted in the feces so this is how bile acid resins work also it is good to know that after statins as 8mi are the second most commonly prescribed drug because it is it is showing

Good results in the recent studies published so that was about the by ezetimibe and bile acid resins now let’s try to understand the side effects of both the drugs the side effects are every medical students favorite side effect those are nausea vomiting and diarrhea these are the common side effect other than that bile acid resins will cause decrease in the fat

Soluble vitamins yeah that’s the main mechanism it decreases the fat soluble vitamin and yeah uh this as the time i’ve also causes the idea so this is it now one thing that you need to remember out of all this is that bile acid resins increases the triglyceride level and it is the only lipid lowering drug that that can cause increase in triglyceride levels so i

Try to remember it like this bile acid raisins raises the triglyceride this is how i try to remember it raisins it raises triglyceride now let’s try to understand briefly how that works so whenever there is decreasing bile acid reabsorption three enzymes are affected and those enzymes are phosphate ik acid phosphatase cholesterol seven alpha hydroxy less and hmg

Coenzyme a reductase out of all these phosphatidic acid phosphatase is responsible for triglyceride synthesis and this is the reason the activation of this enzyme that results in increase in triglyceride under the effect of bile acid resins so yeah that was all about acetamide and bile acid resins now let’s try to compare to mold drugs now before comparing the two

Motors let’s let’s try to understand one simple principle but it’s very very helpful to understand the mechanism of action of those two drugs let’s say this is blood vessel this is adipose tissue now there is triglyceride in the blood vessel that is triglyceride in the adipose tissue now if the triglyceride wants to move from blood vessel into the adipose tissue

The enzyme that will help this is called lipoprotein lipase right so lipoprotein lipase it breaks down the triglyceride into free fatty acid and glycerol and then it moves to adipose tissue the opposite is true for another enzyme if the triglyceride wants to move from adipose tissue into the blood vessels then it is done by an hormone which is called oh sorry by

The enzymes which enzyme which is called hormone sensitive lipase so let’s try to think by common sense if we decree if we want to decrease triglyceride levels in the blood what should we do either we should increase the activity of lipoprotein lipase or we should decrease the activity of hormone-sensitive lipase and that’s what five dates and nia’s hinders

Fibrates basically increases the activity of lipoprotein lipase so more triglyceride is being transferred from blood vessel to adipose tissue and the triglyceride levels in the blood vessel will decrease exactly opposite is true for niacin niacin will inhibit the hormone sensitive lipase and this will cause a reduction in triglyceride in the blood vessel so

This was the simple mechanism of fibrates and niacin now let’s try to understand that in a big detail here i’ve written the mechanism of action of fibroids fibroids they bind with pper alpha which are basically transcription factor i don’t want to go into the detail of this thing because it is not that much held but definitely you need to know the mechanism how

It works so fiber it binds ppa ppa are alpha which causes activation of ppa or alpha now this combination of fibrate and ppa our alpha will affect the peroxisome proliferator response element and this peroxisome proliferator response element which will cause increased expression of lipoprotein lipase and that’s how it will decrease the triglyceride levels also

This thing increases the production of apple ipod protein even and fo lipoprotein a1 is a major component of hdl so this will cause increasing hdl production now let’s go to the fibrates side-effect the five first side effect is myopathy and it is extremely high also myopathy is more severe when it is come when these settings are sorry fibroids are combined with

Statins so you definitely do need to remember now i try to look about on the internet i tried to search various articles about the side effects of fibrates how does it cause myopathy but there is no clear and concise explanation anywhere so if i will find the explanation about myopathy i will definitely add it in the next video so yeah the first first side effect

Is myopathy now the second side effect is it forms cholesterol gallstones there are two main responsible two main mechanisms which are responsible for forming cholesterol gallstone that cost one is there is inhibition in seven alpha-hydroxy lives now what’s the purpose of seven and hydroxyl is 7 alpha hydroxyl is so 7 alpha hydroxyl is is the first enzyme is

The first enzyme involved in bile acid synthesis and it is also the rate-limiting enzyme it forms seven alpha hydroxy cholesterol and then later on it will form bile acid so when this enzyme is blocked by five rates there will be buildup of cholesterol and there will be reduction in bile acid and as we know whenever there is a reduction in bile acid the chances

Of forming cholesterol gallstone increases there’s one mechanism the other mechanism is fibrate simply increases the biliary cholesterol secretion and that causes formation of biliary call stones so these are the two main side effects that we need to remember about the fibers now let’s come to niazi let’s discuss the mechanism flexion of myosin the first thing is

It inhibits the hormone sensitive lipase which will decrease the triglyceride levels now when the trial is red levels will decrease it will cause reduction is in vldl and that will affect the levels of ldl this is the simple mechanism of action of niacin now let’s try to understand the side effects of niacin which are very very often lee asked and it is very high

So the first side effect is flushing flushing and through rytas now initially it was believed that the flushing and pure itis occurs due to predaking in and histamine but this is wrong it does do to prostaglandin especially pro stag lending d 2 and e 2 so that’s how nia sin will cause flushing now to reduce the flushing we can do certain things first thing is we

Can give a spear into the patient that causes detection in flushing also we can titrate that those slowly that will help ended up reducing the flushing and the last thing that we can do is we can use sustained these sustained-release sorry there is no enough space yeah so these are the three things that we can do to reduce the flushing that is associated with me

As in other side effects include hyperglycemia and hyperuricemia the mechanism of hyperglycemia is again not exactly understood there are many hypotheses which you can find on pubmed articles but the exact mechanism is not very clearly mentioned anywhere and in hyperuricemia it simply stops the secretion of power it decreases the secretion of uric acid in the unit

And this leads to increase in uric acid and sometimes it leads to gout gout attacks so this was all about the mechanism of action of fibroids and niacin in next video we will try to discuss other lipid lowering drugs

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Lipid lowering drugs | Pharmacology | USMLE STEP 1 By Meet patel