DIP Episode 432 - Pharmacology Blitz

Okay welcome my name is divine this is episode 432 of the divine intervention podcast into this podcast I'll be discussing a topic I like to call farm blitz from ecology blitz so I know some of you may wonder divine what do you mean by pharmacology blitz basically what I mean is over the next few minutes here I want to try to cover a lot of very high yield pharmacology that will be helpful for anyone taking step one step two or step three I'm just gonna try to tie many things together so I'm not gonna like dwell too much on any one point it's gonna be almost like a rapid review of pharmacology obviously I can cover every single pharmacology in this one podcast but at least I will try to make an attempt to cover as much as is humanly possible so what if they give you a question about a patient and they tell you that this patient has a myocardial infarction and the person got a drug for chest pain and then the person's blood pressure decreases precipitously what should you be thinking about I really hope you thinking about a nitrate remember nitrates they are very important drugs that are used in M Is to deal with the chest pain because you know when you have an amount of your heart is not working very well so you need you know as those myocardial cells are dying you you may experience a lot of pain so that pain one of the ways we treat that pain is with nitrates and nitrates they help by being puffle vino dilators since they are puffle vino dilators they would send less prelude to your heart so your heart doesn't have to work as hard since dealing with less fluid and it will help that's how nitrates help especially even in people that have angina they reduce myocardial oxygen demand but if you have an RCA infarct nitrates are not a good idea they are not a good idea so remember nitrates again the cause nitrate oxide release okay maybe let me explain so they're not a goo

d idea because in RCA infarcts you need pre-load bad so if you're taking a vino dilator you're killing that pre-load you're gonna get in a lot of trouble because those people are effectively not taking blood to the right side of the heart but the right side of the heart is already dysfunctional because they have an RCA infarct that's what caused this precipitus drop in blood pressure in this in this patient so remember nitrates they work by causing nitrate oxide release so they cause a lot of visual dilation again they are predominantly vino dilators and don't forget they work primarily through the cyclic GMP system the cyclic GMP system so they cause visual dilation but again more specifically they're working in in veins than arteries and remember these things because they are very powerful visual dilators they can cause a lot of like hypotension cause a lot of flushing cause a lot of headache right remember headache is medialed by visual dilation I believe that's a mechanism of explained I guess I'm kind of catching myself going off in all these directions now what I think is just better than just flying through things let me just make sure that you can understand at least even a little bit like talk about use this principle before again I'm gonna try to integrate with other drugs I've used this because this principle before I believe in an older podcast that visual dilation causes headaches visual constriction treats headaches for example I like to think of it this way nitrates they are visual dilators they can cause you to have headaches but look at people when you have a headache what do you take usually take an insect how do the insects work?

Insects are cycloxygenase inhibitors the inhibit cycloxygenase when inhibit cycloxygenase you'll make less prostaglandins prostaglandins are visual dilators so you're making less of a visual dilator by making less of a visual dilator you're gonna get visual constriction if you also look at it from the perspective of migraines like taking drugs like the sumatriptans and your gota means those things are very powerful visual constrictors they are very powerful visual constrictors remember those drugs by the way especially sumatriptan is a serotonin agonist it's not gonna be a very good idea in a person that has is taking a serotonergic agent so just be careful there a sumatriptan can be a cause of serotonin syndrome in a patient just be mindful of that so those drugs are very powerful visual constrictors since they're powerful visual constrictors they're very helpful for reducing the the migraine problems that people could have because again essentially causing like a visual constriction in the brain and then that should inform you why people that have a history of visual spastic disorders should not be on drugs like sumatriptan it will not be a good idea because again if you have a visual spastic disorder like Prince Meda-Langina which would cover and tangina these days or you have renounce phenomenon just if you have like visual spasim in a vessel it's not a good idea to be taking sumatriptan because again those things just as well as the cause of the visual constriction in a person's brain they also cause visual constriction in the very very that can cause problems if you have a visospastic disease so again I guess we've kind of talked about four or five drugs just from talking about nitrates but again nitrates we used them for angina and you get tolerance to nitrates very quickly that's why it's very important to take like a drug-free holiday of some sort now what if

they give you a question about a person that is on a bunch of cardiac drugs and you notice you know let's say they have metabolic disease or diabetes or whatever and they notice that those people have radiating well again I'll really be thinking about statins so remember how do statins work statins the inhibit-h-energy queer inductees the inhibit-h-energy queer inductees so because the inhibit-h-energy queer inductees they're gonna prevent the synthesis of cholesterol that's how they're hypolypidemic agents they're basically gonna reduce the synthesis of LDL so if you reduce the synthesis of LDL within the hepatocyte for example then the thing that's gonna happen is your intracellular hepatocyte LDL concentration goes down so what is like man I'm gonna need more LDL from the very very so you're gonna express more LDL receptors on the surfaces of your hepatocytes and that's gonna cause you to bring in more cholesterol more LDL cholesterol into the cell and if that happens if that happens then your blood cholesterol levels are gonna go down remember the statins they are the best at reducing LDL but don't forget these things they are gonna decrease the synthesis of coins and Q so you can have some muscle dysfunction if your muscles are not working properly you're gonna have an abdominal myelosis those muscles cells are gonna start breaking down if they break down you're gonna have red urine you're gonna have red urine you're gonna be seeing a little myoglobin in the urine so you're gonna see like three or four plus blood but you're not gonna see a commensurate number of red blood cells because of that's that's an induced toxicity so that's something you kind of want to make sure you keep at the back of your mind for exams and then what if they give you a question about a person that is taking a supplement because they want to try to get healthy because let's say the doc

tor told them that oh your your LDL is really high and your HDL is really low so instead of taking a supplement well I really hope you're thinking about an ISN in that circumstance so ISN remember it's very good at lowering LDL but it's the best at raising HDL in fact one thing our friends at the MBM is love to test on exams is they love to test who is the best at doing XYZ there are certain things you need to know here in terms of raising your luring your LDL luring your LDL starting at the best in terms of raising your HDL niacin is the best in terms of luring your triglycerides your fibres are the are the very best your fibres are the very best at luring your triglycerides just want to keep that in mind for any of the exams so remember niacin again it's the big thing there the big story days are is in HDL and again the thing is niacin can cause flush it niacin can absolutely cause flush it niacin can absolutely cause flush it one of the easy ways to remember that is that if you think of a person that has a lot of serotonin being meeting their buddies because they have carcinoid syndrome remember one of the things that happens with carcinoid syndrome is that they have bronchospasib they are flushing they have diarrhea and they have right side of heart problems flushing because they have that serotonin excess where the serotonin comes from serotonin comes from triptophan serotonin comes from triptophan and niacin is also derived in a way from triptophan as well so you can kind of see an interrelationship there that may be the easiest way I would say for you to remember that when a person takes a lot of niacin they can actually get flush in flush in as a side effect and then what if they give you a question about a person and they tell you that this person you know they were studied on statins for the diet for for hyperlipidemia but the LL was not brought to an accept

able range so another drug was added was since that drug was added they've been having a lot of false million stools they've been having a lot of floating stools but if you see stuff like that I want you to think about the bile acid binding reasons so something like cholesterol remain cholesterol cholesterol am this is a bile acid binding reasons so they they basically bind bile acids in your GI tract in the lumen of your GI tract which is good which is good because if you bind those bile acids then you're basically messing up this process of enter a hepatic recirculation if you remember maybe from early med school you probably remember learning about this thing known as enter a hepatic recirculation where you basically start with that some of the bile you make you're gonna actually reabsorb some of it in the GI tract so the thing that happens is if you bind up those the bile with the bile acid binding reasons like cholesterol cholesterol or cholesterol or cholesterol or cholesterol or cholesterol you're not gonna recirculate it back you're not gonna reabsorb it back so if that happens is almost like if you're thinking in terms of Lushakli's principle you're driving the more excretion of bile acids so your body is gonna be like wow I'm not seeing bile acids here let me keep making more keep making more as you make more more bile acids what do you think bile acids come from they come from cholesterol they do come from from cholesterol they do come from cholesterol so in that way you're gonna be lowering your cholesterol in your body and progressively because it's almost like you're I just think of it as an equation bile acids on one side of the equation cholesterol on the other side of the equation if you keep that's recirculate those recirculating bile acids almost keep like a equilibrium of some sort so your body is gonna be like wow okay these bile acids I'm not see

ing anything on the other side of the equation so I'm gonna keep driving their formation so if you're driving the formation of more more bile acids well guess what you're gonna be utilizing your cholesterol more and more so you're gonna be lowering your cholesterol more and more that's literally how bile acid binding reasons work and actually being very good for for lowering the presence of LDL for example but again you can already begin to see that this could potentially cause problems because if your body is then generating more more bile acids we remember those bile acids are generated in your liver and all those bile acids are gonna be excreted into bilirubin they're gonna be excreted into the stuff that comes out through your through your ducts your bilirium system all the way to the duodenum so if you're making more more bile acids those bile acids that you're making more and more of because your body is like wow I'm not seeing them be recirculated back you make it more and more of them it can saturate it can saturate your bilirifluid and you can get gold stones you can get those deep pigmented those unpigmented gold stones and again obviously bile acids if you're hanging out in your GI tract for longer than these should hang out it's gonna cause you to have a malabsorption you're gonna have a nasty diarrhea so it's not necessarily the best thing in the world and then don't forget that cholesterol means it's actually a very good adjunct you can add in a person that has cdif colitis it's actually very good at binding on the cdif toxin so if we're talking about cdif what do we use to treat cdif or remember we treat cdif with oral vancomycin or you can use phidaxomycin vancomycin I'm gonna give it orally because it has to concentrate within the lumen of the GI tract to kill the cdif has to concentrate within the lumen of the GI tract to kill the cdif so I guess my

question for you then is how does vancomycin work how does vancomycin work?

Well vancomycin the way it works is that it essentially binds to diala diala and when it binds to diala diala which is found in the cell wall of especially your gram positive organisms it binds to diala diala when it binds to diala diala then your enzymes that help you build your cell wall like transpeptidys they will not be able to bind to it because literally transpeptidys it's job is it takes diala takes diala kind of brings them together and bone makes a new cell wall but if for some reason there's someone hanging out on diala diala and transpeptidys cannot bind to it then you're gonna get in a lot of trouble you're gonna get in a lot of trouble you're gonna get in a lot of trouble not you but those bugs who get in a lot of trouble so the critical thing then is our friends at the NBM is the contents okay well you know the mechanism of action of vancomycin great and then they give you a question about a person the person has a significant gram positive infection gram positive sepsis and the person got vancomycin what days after getting vancomycin therapy the person's clinical condition is getting worse they're still having fevers they're still having leukocyteosis they're still having all these problems and then you can see what's the make what's the most likely theology of this of this phenomenon that you observe it but I would really hope you're saying that's that diala diala was converted to diala de laac right so again remember you need two alamines next to each other for vancomycin to bind if you have alamine a lactate next to each other then vancomycin cannot bind that's how you get vancomycin resistance that's how this whole term of versa vancomycin resistance staphoreos OVR even coma is a resistant interococcus kind of comes to light so that's something I want to keep in mind again one people do integrate these things together one people will put all these

things together so that's how vancomycin works that's how vancomycin works that is exactly how vancomycin works and then what if they give you a question about a person they tell you that this patient comes to the emergency room because they've been having a bigastric pain that's radiating to the back and then they tell you that this person does not have a history of alcoholism but that the person is very obese and they you notice that this person's triglyceroid is in the thousands well what's going on there well I hope you're telling me that would a vine this sounds an awful lot like hyper triglyceridemia induced pancreatitis so what are we gonna use to treat hyper triglyceridemia induced pancreatitis well you're gonna go ahead and use a fiber it's a fiber it's remember fiber it's they have like a pretty classic name in skin you know they all end in either fiber it or the end in fiber so like phenol fiber it's chlorophyberate gem fiber cell those are their classic names I remember these things how do they work how do they work well the way they work is that they operate like upper protein lipes so by operating like upper protein lipes well like upper protein lipes what in the world does it do is job is to bring down triglycerides so if you bring down triglycerides more and more and more if you bring down triglycerides more and more and more then you reduce the on levels because remember hyper triglyceridemia can absolutely cause pancreatitis again don't think only of gallstones and alcoholism as the only causes of pancreatitis you could see on your exams there are many things that can cause pancreatitis they are drugs that can cause pancreatitis especially some of the diabetes drugs you'll see if you want to get a DPP for inhibitors they can cause pancreatitis you'll HIV drugs stavidine didano syndrome they can cause pancreatitis mom's the virus so you can give you a

question about a child with big big um big jaw and big testicles and of course they'll put fragile X syndrome as one of those answers which will be wrong but then they'll put moms moms can also cause acute pancreatitis so remember there are many things that can cause acute pancreatitis but hyper triglyceridemia remember even acute pancreatitis it can give it to you as a question and I'll get back to the fibres in a bit but again I'm trying to mix some more integrations here but it can give you a question about a child that hits his belly on a table and then they start in this epigastry period it's into the back again that can be a cause of pancreatitis remember these handlebar injuries if you hit your belly especially your epigastrum very forcefully on a hard surface that can cause like it's like blunt force trauma to the pancreas that can absolutely positively cause acute pancreatitis it's something you just want to keep at the back of your mind for example so remember fibres how do they work again fibres they operate lipoprotein lipase remember lipoprotein lipase it's job is to bring down triglycerides so if your lipoprotein lipase is revved up your triglycerides are gonna go down because they have been more effectively metabolized they've been more effectively metabolized but again remember these drugs they can cause a myopathy just like statins they can cause a myopathy in fact combining a statin and a fibrate is usually not a stellar idea on the US Meli exams because that can absolutely cause problems problems with the patient so remember statins and fibres they can cause a myopathy and they can also be hepato toxic they can cause a myopathy and they can also be hepato toxic they can cause a myopathy and they can also be hepato toxic to be honest with you some of you may be like divine how do you remember these side effects so well to be honest with you sometimes

one of the best ways to remember side effects of things is to just remember what organs in the like riddles this drug actually work like for example I'll give you a classic example like metformin many people are like oh gee if your liver doesn't work well can't take metformin if your kidneys don't work if you have like chronic kidney disease or whatever can't take metformin hmm what do you think that is well ask yourself how exactly those metformin work how exactly does metformin work we know that metformin works by inhibiting hepatic glucose in eugenesis basically the big thing to know about metformin is that it inhibits gluconeogenesis okay well let me ask you a question we're in the world those gluconeogenesis happen we know that gluconeogenesis for sure happens in the liver and we also know that gluconeogenesis for sure happens in the kidneys many people forget this but the kidneys actually capable of gluconeogenesis they are capable of making glucose that can be distributed to other organs in the body they are capable of doing those things so if we know that metformin sites of action primarily and the muscle I mean sorry I'm in the kidneys and in the liver then it would make sense that if your kidneys don't work well or your liver doesn't work well you're gonna be pretty exposed to metformin toxicity and since we've kind of talked about metformin remember sometimes is a put in metformin as an answer in the exams you know our friends at the NBA knees they love this whole concept of derivatives they're gonna use the term big one-ites big one-ites that's the drug class for metformin again our friends at the NBA knees they just occasionally like using terms that are different from what you're used to so don't forget metformin metformin metformin can essentially inhibit a gluconeogenesis so if you inhibit gluconeogenesis then it's basically increasing your glucose se

nsitivity in a sense actually there's another thing there with an amp-dependent kidneys that metformin also activates that amp-dependent kidneys mix your body use glucose without insulin because remember the big problem with diabetes is that your body is unable to use insulin effectively you either have no insulin that's type 1 diabetes you have an insulin resistance that's type 2 diabetes although over time if you have type 2 diabetes you know ameloid is gonna build up in your pancreas in the form of amelene and then it's gonna mess up your pancreas so you're gonna at some points develop an insulin deficiency that's why if people have type 2 diabetes for long enough they're gonna need insulin at some point so the thing is metformin essentially provides your body an alternate pathway to utilizing glucose in a non-insulin dependent fashion that non-insulin dependent fashion is by this amp-kindness amp-kindness is a kindness that causes you to use glucose without needing insulin literally without needing insulin if I'm not mistaken actually believe that amp-kindness is something that comes into use when you're exercising because when you're exercising you need a lot of glucose and you need that glucose really fast so you know your body one of the ways it tries to really revel how much glucose you have available is by using that amp-kindness that amp-kindness actually a pervulated when you exercise that's actually a truism I don't know if truism is a term but whatever but essentially if you're using that amp-kindness more and more and more and more then it's almost like your body is able to deal with that hyperglycemia problem that you have in diabetes but it's not using insulin to do that so in that case you become more insulin sensitive in that case you become actually less dependent on insulin because your body is like getting all this good utilization of glucose even

if your insulin may be very limited that is around so that's how metformin actually increases insulin sensitivity and that's also why if you exercise you can actually reverse diabetes because by exercising you know I operate more amp-kindness about regulating more amp-kindness you're gonna be utilizing glucose more effectively using more effectively and you're not gonna have that much of a blood sugar problem that can actually really help over time in diabetes especially when you do it with some level of consistency so many people also memorize that oh divine you know I've learned that metformin and coltlactica sedoses well let me ask you this how do you think it causes lactic acidosis we think about it again it all comes back to understand in the biochemistry all come back to understand the biochemistry we know we know we know that metformin inhibits gluconeogenesis so because metformin inhibits gluconeogenesis think about it when do we operate gligligluconeogenesis we operate gligligluconeogenesis when we're in situations when we don't have enough energy and lactic acid is a good marker in the body for not enough energy it's a good marker in the body for not enough energy because if you think about it why would you be generating lactic acid you be generating a ton of lactic acid because you've depleted you've been running is almost like you're like man I need I need energy bad so you know what even if I cannot block the day for its relation I'm gonna at least look like all of this and make a lot of lactic acid so what does your body do with that lactic acid or your body takes that lactic acid converts it back to pyruvate and then takes it up that gluconeogenesis pathway to go back and reform glucose in the process of gluconeogenesis so think about it if you short down gluconeogenesis then everything that feeds into that gluconeogenetic pathway is gonna stop buildin

g up it's literally gonna stop building up and if those things that build up that's gonna cause you a lot of problems it's gonna cause you a lot of problems and then one of those things that can build up is lactic acid one of those things that literally can build up is lactic acid so that can cause a problem that's actually how metformin causes a lactic acid doses that's a logical way to visualize it in your mind.

One thing I want to say real quick as before I continue is again if you like the way that I integrate things then you may be interested in some of the review courses I offer for people that are taking the USMD step one exam actually have a course coming up next week actually I believe starts next week Thursday it's gonna be from the fifth to the seventh of January and from the ninth to the tenth of January I believe we're gonna do it Thursday Friday Saturday and then we're gonna take a break on Sunday and we're gonna meet on Monday and Tuesday it's five hours each day is 25 hours total and again if you like the way integrate things across many disciplines the way I present things in a form that is not just a lecture but I present you a clinical context and scenarios then that step one class may be something that you're looking for so 25 hour class and also if you're a person that just is taking step two or step three and you have an awful basic science foundation the step one class is precisely what you need and then by the way I also have a few other classes running in the month of January I have an MB Me test against strategies class is for step two and step three but it's also intended for booticking step one because step one has a lot of clinical questions and allows in those clinical questions appropriately this test against strategies class will help you for that that's gonna be taking place on the 20th of January and then I have social sciences and ethics class it's a five hour class taking place on the 12th of January social sciences and ethics for all the USMD exams is not about 10 to 20 percent of each of each form of each exam so if you want to get a very solid basis and again I'm not gonna be giving lectures gonna be presenting scenarios and showing you how to apply and integrate the knowledge then this class may be something you're you're looking for and t

hen I have the 20 hour review course that's for step two and step three and complex two and three also if you're a medical student you're 30 a semester you're like you know what I want solid performance shelves I want to see a lot of the high-quality information I'll show them myself exams in the 20 hour courses what you need it's gonna be taking place on the 23rd and 24th and on the 26th and 27th of January 20 hours five hours four days five hours each day for four days and then you know I also have the biostatistics bootcamp which is very popular many people have taken it and they found it to be tremendously helpful it's gonna be held on the 30th of January it's gonna be held on 30th of January so if you're interested in any of these classes just shoot me an email and I'll give you some more some more information and during these classes I make a point to spend time answering people's questions about one sixth of the total class time is been answering questions and I try to go at a very decent pace so people can take take a very very good very good notes so if you're interested in any of these things just shoot me an email and I'll be more than happy to point you in the right direction so we're talking about informing right so we're saying that informing Lactic acidosis is a big side effect and we're kind of talked about the mechanism behind those that that side effect so again how can our friends at the MBM is go after informing some more well when we they can go after informing some more is they can come after it from the perspective of contraindications but it will make it like a clear caught contraindication they'll make it like a round about contraindication like for example if a person comes into the hospital in shock and they have diabetes do you think he's gonna be a very good idea to be giving those people met forming probably not because again when you hav

e shock you're not profusing your system your system's tissues very well if you don't profuse them very well then you're gonna be depending a lot there's gonna be hypoxia if there's hypoxia well your electron transport gene is not gonna be working very well and if it doesn't work very well then your TCE cycle is not gonna be working great either so your body is gonna be like well I'm not getting enough oxygen I need to depend on something that can help me with my oxygen I need to make energy in some way that is non-oxygen dependent well what does that sound like that sounds a lot for look like glycolysis so when glycolysis is happening at an increased rate you're gonna generate more Lactic acid again that Lactic acidosis can potentiate the Lactic acidosis you can get from from met forming so just you you kind of want to be careful with that because if a person has a condition where they are generating more Lactic acid that's almost like a barometer for ooh this person's tissues are not being well profused well at least whatever little profusion your tissues have you want those tissues you want that blood moving around in your body even if it's little even if it's little even if it's little to have some measure of glucose in it so it's not particularly smart to be inhibiting glucose in your genesis at the precise time where your body needs more glucose so again met forming not a smart idea in people that I'm shocked met forming not a smart idea in people that are getting a remitted contrast if you're getting a remitted contrast you're literally giving something that can sacrifice a presence kidneys again if you're giving a kidney sacrificial agent you should not be giving people drugs that depend on proper metabolism in the kidneys to function again you just kind of want to be careful of of some of these some of these things and then again we've talked about in terms o

f the lipid drugs we've talked about the nitrates we've talked about the statins we've talked about niacin we've talked about the bilacid binding raisins we've talked about the fibrates we've well the nitrates they are not really a lipid drop but that's how I kind of kind of started I kind of started but again don't don't forget your azetamide pretty your drugs like azetamide is that a my is a drug that basically prevents the reabsorption of cholesterol again if you don't reabsorb cholesterol ultimately your hepatocytes are going to be like wow we don't have enough cholesterol going so what is going to express my LDO receptors on the surface of your hepatocytes and that's going to bring more LD Ls going to clear more LDL from the from the circulation so again one thing I think I want to say as I you know as I proceed further here is one thing our friends at the Mbim is love to do in terms of statins let me maybe throw this in here in terms of statins many times they will not put HMG query doctors inhibitor as the answer to how does a statin work they can literally put an answer that says increases the expression of LDL receptors on the surfaces of hepatocytes so that's something you want to keep in mind that may not be directly how it works but that's indirectly what it achieves because basically if you again make less cholesterol because you've killed HMG query doctors your hepatocytes will have a low intracellular cholesterol concentration that's going to cause them to say you know what since we can make cholesterol we got to get that cholesterol from the periphery so they will express more LDL receptors so you have increased cholesterol clearance from the bloodstream from the periphery that's how those things lower LDL that's how those things lower LDL that's how those things lower LDL so again instead of putting HMG query doctors inhibitor one answer they can easil

y put is lowers intrahepatic concentration of cholesterol another answer they can put is increases the expression of LDL receptors on the surfaces of hepatocytes one other answer they can just put is increases LDL clearance from the periphery notice literally I'm seeing the exact same thing I just literally said it for different ways that's the concept of derivatives with the USML exams they take what you know and just put it in other forms just to see if you truly understand what's going on so again that's why you see me I keep telling people there's nothing wrong with Anki Anki is amazing even for me as a person that has been involved in education for a long time I see the intrinsic benefits of Anki but again don't just memorize stuff you need to understand what's going on many people already having their brain is their brain is filled with buzzwords if your brain is filled with buzzwords you could have done well on the USM Ls of back in the day but that's not the case with the USM Ls of this present time your brain you cannot have a buzzword field brain and succeed on your USM Ls no you need to have a brain that yes has buzzwords but also some of that space should probably more space than the space you're looking to the buzzwords should have understanding there because is that understanding and ability to integrate that can really really help you knock down questions on exams like you see some people they struggle bio stats because they have a formula field brain if you have a formula field brain yeah you may answer like a few of your bio stats questions on the exams or you may be lucky and get a form that has just plug and chalk but the thing is many of the bio stats questions these days are not plug and chalk if many of them do not involve math at all many of them are like word problems or you actually have to like raise it out and even realize that this is what the

y're testing from the scenario like literally there are questions that will show up on an exam on an exam on a USML exam you read them is a bio stats question and people do not even know that is a bio stats question or if they realize that it's a bio stats question they do not even realize the concept that's being tested they think that this question is talking about negative predictive value when the question is talking about specificity but the thing is all they know about specificity is the formula they don't know how to integrate specificity they don't know how to reason through specificity like literally the imbim is character a D-dimer question and it's literally a bio stats question again you got to learn to reason through these things you got to learn to reason through these things and since I guess we're talking about the LDR receptor we're saying that if you express more LDR receptors on the surfaces of your hepatocytes then you clear more LDL from your circulation if you clear more LDL from your circulation then you're going to lower your LDL so that means persistence of the LDR receptor on the surface of a hepatocyte is a good thing it's literally a good thing so what is the thing that makes those LDR receptors to be endocyte toast and recycled well it's an enzyme known as a an enzyme known as PCSK9 so PCSK9 you know it basically does what you don't want if you're trying to lower your LDL literally its job is to cause you to endocyte to set LDL receptor and then break it down your body doesn't just lose all the proteins and amino acids and everything in the LDL receptor it actually does recycle them so it kind of reduces the number of LDR receptors if you may on the surface of your hepatocyte so what is one effective with account of that problem well one effective with account of that problem is to shut down PCSK9 if you shut down PCSK9 then your LDL recep

tors will have almost like a bigger longer half life on the surface of your hepatocytes in a sense so that's where drugs that all end in cum up right like if a low cum up and a low cum up the PCSK9 inhibitors that we use to actually manage a presence hyper lipidemia okay so I think I'm gonna stop this farm blades podcast you know we'll see what happens in the future with timing my schedule and stuff I'll be happy to maybe have another farm blades podcast I think this is actually a pretty good format you get to review a lot of not just farm a lot of pathology a lot of physiology one of pathophysiology very very short time time time frame so I'm gonna go ahead and stop here again I go for one of one tutoring for the USM in exams step one to three pre-clean cool medical exams third year shelf exams I'll review courses for step one I literally have one study next week for step two and step three I literally have one studying next next month I have a biostatistics bootcamp I have a social sciences and ethics review and then I also help with applications mock interviews rec letters personal statements things like that so if interested in any of those things just shoot me an email and I'll be able to point you in the right direction I also have a this podcast on the three major podcasts apps Apple podcasts Google podcasts and Spotify at least the first the first three at least those major three three apps at least the most recent 150 podcasts are on there really if you want everything from episode one to four thirty two you got to go on the website those podcasts apps they just don't really let you put more than 150 episodes at the time and then I have a You Tube channel the right intervention you're semi-podcasts and videos that's why I post the videos I make and actually I've been uploading a lot of of my podcast material as well on that You Tube channel so please subscribe

to that You Tube channel just every bit of support certainly helps and please spread the word if you've got any benefit from this podcast don't don't hide it you know don't hide it for yourself you know spread the word with other people and then I also have another website called divine intervention life lessons.com that's a website where I post the life lessons that I meet many people say that wow divine I love the life lessons that you post at the end of some of your mainstream podcasts but so I decided to make a new website divine intervention life lessons.com in fact there's an Apple podcast associated with it if you look on Apple podcasts it's called the divine intervention life lessons podcast and it's Bible based you know every week I post two podcasts that tend to 20 minutes long and they address like just a common problem that people face from a biblical perspective so again I really hope you find we find that to be to be helpful so thank you for listening to me today again as as we wrap up the year I mean that today is December 29th I'm just going to encourage you you know even if you've screwed up I mean today is December 29th so we've gone through like 362 days already around the 363rd day if there are things if there are stones that you've left unturned all throughout the year you still have three days to turn those stones if you're moving in the wrong direction all throughout the year you can make a change now the thing is many people believe so heavily new years resolutions again there's there's nothing wrong with new years resolutions so I guess there's a life lesson and there's nothing wrong with new years resolutions but the time to make a change is now not when the new year starts you see some people they literally want to wait till the new year let me tell you this the more time you spend going in the wrong direction the more time you will spend hav

ing to reverse those bad decisions that is the truth that's why to be honest with you again nothing wrong with the concept of a new year's resolution is fine but you don't have to wait till January 1st to start making a positive change in your life you can make a positive change in your life starting now there's even this part of the bible that says now is the time of salvation like literally now not tomorrow not next next year but you let me tell you this you you can guarantee tomorrow you literally cannot guarantee tomorrow and you may not even realize this an opportunity that you're like well prepare for that opportunity with my new years resolution it can be an opportunity that shows up for you on December 31st but if you are prepared on December 29th and 30th you can take advantage of that opportunity that shows up on the 31st so I'm telling you like maximize your time maximize your now don't waste your now don't keep looking looking looking looking to start maximizing the future and then you're under utilizing the present that's not a small idea because think about it see for example you're supposed to take an exit on a highway and then you don't take that exit and you keep driving driving driving till 10 exits later yes you can still get back to your original position but it's going to take you a longer time to get to your destination that's the same thing with people that keep saying well I will make a change next month I'll make a change next week I'll make a change next year that time will probably never come that time to make a positive change in your life is literally now take that exit now if you take the exit now at least whatever backtracking you need to do from the mistakes you've made all along the backtracking period will be shorter versus a longer backtracking period yeah because there's this intrinsic motivation you see people have like wow once th

e new year comes I'm going to change my ways I mean no it's not the new year comment that will make you change your ways is you truly changing your ways that will make you change your ways or you see some people they are like oh if I move to a new city you know all these problems will disappear now I mean yes there are sometimes rare movies warranted but many times all people need to do is sting the same spot they're in but just make a change sting the same city but make a change and their lives will get better but I think I'm going to go ahead and stop here you know this is almost 40 minutes already but just make a change you can start your resolution now you don't have to wait three more days to start that resolution so thank you for listening to me I hope you're blessed by this podcast I'll see you in the next episode God bless you bye for now thank you

Nitrates; they release nitric oxide (NO), causing potent vasodilation.

Because the profound venodilation will decrease preload, potentially leading to severe hypotension and worsening cardiac output.

Inhibition of HMG-CoA reductase, which prevents cholesterol synthesis within the hepatocyte.

Niacin (Nicotinic acid).

They activate lipoprotein lipase (LPL), enhancing the metabolism and clearance of circulating triglycerides.

Lactic acidosis, because inhibiting gluconeogenesis can lead to an accumulation of lactate if tissue perfusion is poor.

Statins (e.g., Atorvastatin).

They bind bile acids in the GI lumen, preventing enterohepatic recirculation and forcing increased excretion of cholesterol-derived bile acids.

Oral Vancomycin (or Fidaxomicin).

PCSK9 (Proprotein convertase subtilisin/kexin type 9).

Fibrates.

Hepatic gluconeogenesis.

Statins (e.g., Atorvastatin).

They bind bile acids in the GI lumen, preventing enterohepatic recirculation and forcing increased excretion of cholesterol-derived bile acids.

Oral Vancomycin (or Fidaxomicin).

PCSK9 (Proprotein convertase subtilisin/kexin type 9).

Fibrates.

Hepatic gluconeogenesis.