Antiplatelet Medications | Mechanism of Action, Indications, Adverse Reactions, Contraindications

what's up ninja nerds in this video we're gonna talk about antiplatelet medications this video is brought to you by the great courses plus it's an on-demand video learning service that's gonna help you to further your knowledge and understanding in various different topics things that we are here an engineering science don't really cover things like cooking photography history so as a student and as someone who's trying to further my knowledge I'd love to use as many resources as possible to help me to be a very good clinician I think the great courses plus would be a great addition to you guys's repertoire so if you guys can't go check it out they have an eleven thousand plus video library where you guys can watch videos such as like something on the immune system by dr. Anthony a goodman the great courses plus is offering you a free trial so go check it out at great courses plus.com slash an engineered science also if you guys want we'll have a link in the description box all right so it's gonna get started alright engineers so let's go ahead and talk about these different antiplatelet medications and an order for us to really know all the different types of antiplatelet medications it's best to look at them based on their mechanism of action right so first thing we have to do before we really get into all these medications is just the most basic overview of hemostasis if you guys remember endothelial cells what was their function generally they were supposed to release specific chemical substances that keep the blood and Chi thrombotic right if you guys remember back from that video we had molecules like PGI two molecules like nitric oxide and if you guys remember what these little guys were doing is they were basically in activating the platelet right so they were keeping this little dude inactivated so that he doesn't attach to the endothelial lining and cause a clot that we don't want well if someone has let's say damage of the blood vessel lining right for whatever reason what's that going to do to the pgi2 and nitric oxide production it's going to decrease what's going to happen to the inhibition on the platelet it's going to be lost so what's the pletely going to want to do then it's gonna want to attach to the endothelial lining so let's say that there is damage and you guys know that never there is damage to the endothelial lining the underlying collagen becomes exposed this little blue stuff here right and what happens is there's a protein that binds within that collagen meshwork and if you guys look here I should be able to name it out it's called von Willebrand factor right it's made by the endothelial cells it can even be made by platelets what happens is this von Willebrand factor is like glue to the platelets the players love it they have a specific protein that allows for them to bind on to that von Willebrand's factor you know that little suckers called the little pink guy that is called gp1 B so these little pink proteins here are called G p1b proteins okay and what these allow for is they allow for this connection between the von Willebrand factor and the platelets so that's really important gp1 B is the connection between the von Willebrand factor and the platelet now when the von Willebrand factor binds with the platelet the platelet has to let other platelets know to come to this area of where injury is so that they can attach as well how does it do that if you guys remember we have little granules inside of these platelets different types of granules we're not gonna go into crazy detail there is alpha granules they release things like clotting factors and PDGF which is called platelet derived growth factor but the more important one is the delta granule or the dense granules in these Delta granules they release multiple different types of substances for example they can release three really important ones okay serotonin which is also kind of written as 5-hydroxytryptamine 5ht there's also another one called ADP and you can also release calcium but there is another one that's made by the membranes and we'll talk about that one and a little bit here called thromboxane a2 and if you guys remember from that hemostasis video these guys are platelet aggregate aggregation agents right so in other words they tell other platelets to come and come stick to this platelet but how does this platelet stick to this platelet there's got to be a way right well look here you see these little blue guys here these little blue guys here are called GP now hold onto your tail you to your seats these guys are long GP to be three a proteins ok so here's a GP to be three a protein on this platelet and here is a GP to be three a protein on this platelet what is this little stuff connecting between them this little stuff between them is called fibrinogen right so it's called fibrinogen fibrinogen is going to be like a little glue between these two proteins and it allows for the platelet plug to be stable so again platelet connect to platelet through there's GP 2 B 3 a proteins and again fibrinogen is like the glue between that so that's how they stick with one another how do you trigger their aggregation these little guys so we have medications that are so cool that you can block adp you can break down thromboxane a2 and you can block this protein from linking to one another let's talk about some of those proteins so the first one that I want us to talk about is this thromboxane a2 now if you guys remember I said that the thromboxane a2 is coming from this platelet it's not really coming from the granule it's actually coming from a different type of like acid they call it arachidonic acid let's do this guy here and purple so you have this guy here called arachidonic acid we're gonna put a a here arachidonic acid arachidonic acid is actually going to be broken down through a specific enzyme into it's called prostaglandin g2 then it's metabolized again into prostaglandin h2 is actually going to be metabolized so he gets metabolized into two different components here right one component we're not super worried about it's like your PG e 2 PG f 2 PG d2 and there is another one called PG I those ones were not super super worried about right now the one that we do care about is called thromboxane a2 so it's made from arachidonic acid where does this arachidonic acid come from well you guys know within this platelet you have a phospholipid bilayer that phospholipid bilayer can actually get broken down into different types of fatty acids like a call this Anna Coast annoyed and that arachidonic acid from the membrane can get converted all the way into thromboxane a2 ain't that cool all right so what does thromboxane need to do well when it binds on to this receptor the star on boxing a chi receptor it can activate multiple different types of interesting in the pathways right so it has the ability to activate like a GQ pathway right so GQ if you guys remember will actually shuffle along the membrane and bind on to a specific membrane bound protein here which is called phospholipase C look at this cute little guy yo you know so phospholipase C is actually going to get stimulated by this GQ protein now down to this phospholipase C it's going to break down the specific membrane bound structure here which is called pip2 when it breaks down pip2 it breaks it into two components right one is called ip3 the other one is called da G this is ina SCYTL triphosphate and diacylglycerol ip3 binds on to this little endoplasmic reticulum like Network and stimulates protein channels to allow for calcium to be shuttled out and then the calcium will do what the calcium will then come down here and stimulate these granules and cause these granules to start fusing with the actual cell membrane once it fuses with the cell membrane what happens it starts to release out these little molecules such as ADP such as serotonin such as calcium and again you're going to get more but ilysm of from boxing a to what's gonna happen that's gonna cause more platelet aggregation at the same time da G is also activated what can this little guy do da G can also activate protein kinase is like protein kinase C protein kinase C can then go and regulate this specific protein here which is that GP 2 B 3 a protein and what does that allow for it allows for this protein on this playlet to stick with this protein on this platelet through the fibrinogen glue that's a beautiful thing right so what do we need to block this whole action well we have a drug a very commonly utilized drug that basically inhibits one of the enzymes in this pathway right now watch you know arachidonic acid there's a specific enzyme called a cyclooxygenase that's shortened to Cox and there's different isomers there's a Cox one and a Cox - okay there's a specific drug that can inhibit both isomers okay and it's a beautiful drug a very commonly utilized drug and it's called aspirin or acetyl salicylic acid and what this guy does is if he inhibits he irreversibly inhibits this Cox enzyme let's follow this along if a rock anodic acid can't get broken down to PGG - it can't get broken down to PGH - and it can't get broken down to thromboxane a2 if there is decrease thromboxane a2 there's decreased stimulation of the phospholipase c there's decrease production of i p3 decreased production of d AG decrease calcium getting released from this little endoplasmic reticulum structure and decrease degranulation so decreased degranulation in other words if you decrease the degranulation you decrease the aggregation and activation of other platelets at the same time you decrease protein kinase C and you inhibit okay this actual there's no more stimulation so there's inhibition now and now this GP 2 B 3 a protein on this platelet boat act with the gp2 v3 a protein on the other platelet so there's no stabilization of that clot or that platelet plug that's a beautiful mechanism love that so darn cool okay so we got one one of the big ones here is throne box in a - what about the ADP how does that one important let's go over here so ADP what is this little guy do so he comes over here right you know you have a little protein here there's actually a very beautiful receptor here let's write this receptors name this receptor is called the p2 y12 receptor they call us a p2 y12 that ADP binds on to so what happens is ATP gets released right it binds on to this receptor now this receptor can go two different ways we're going to quickly fly through the pathway one of the proteins that it activates is called AG inhibitory protein that gene hibbett or e protein is going to do a couple different things it's gonna move along the actual cell membrane and it's going to inhibit this enzyme all right what is this enzyme here called it's called adenylate cyclase adenylate cyclase function is designed to be able to take ATP and convert it into cyclic AMP E and then cyclic AMP e will activate a specific enzyme called protein kinase a protein kinase a will then phosphorylate another enzyme let's think of it a really beautiful color for this one oh here's another one this is called vasodilator stimulatory protein vasp okay now what happens is vasp is going to get phosphorylated into what's called vasp p right so it's going to get its phosphorylation there here's what's really interesting with vas whenever it has that phosphorus group bound to it it's interestingly inactive and when it doesn't have that it is active here's what's really interesting what did we say ADP does it stimulates let's follow the whole process here it stimulates the gene hibbott or e protein which inhibits adenylate cyclase that means there's less ATP converted into cyclic A&P there's less protein kinase a and there's less of this vast P being formed okay when this is active what does it do it stimulates the GP to b3 a follow that gene Debra Tori protein less cyclic a and P less protein kinase a less phosphorylation of the vasp into vas P if this is active it's going to stimulate this protein now we just need a drug that can block that receptor and have the opposite effect an antagonistic effect what are some of those drugs I'm glad you asked guys so some of these drugs are called clopidogrel it's a very commonly utilized one brand name is also called plavix okay there's another one called prasugrel which is called eviant there's another one called Tyco a girl or which is called bRILINTA and there's another one that's not commonly used as much anymore because of some of the problems it has you know developed such as T TTP and we'll talk a little bit about that in a TRS but these drugs are basically inhibiting this receptor so if they inhibit this receptor what does that mean that means that there's less jane hibbott or e protein that means that there's less inhibition of adenylate cyclase so that means that instead of having decreased ATP there's actually a slight increase in ATP that means that a little bit more ATP is converted into cyclic AMP e that means you get a little bit more protein kinase a if there's a little bit more protein kinase a then more of this reaction is heading towards this direction and there's actually going to be more of this vast pia and less of the vast so now this is not going to be able to stimulate this anymore so what does that mean there's no stimulation if there's no stimulation then it's going to start to become inhibited and what does that mean that means that the GP to be three a protein of this politely can't bind to the GP to be three a protein of the other platelet it's a beautiful mechanism right there's also another thing that you would just briefly talk about here is that the gene hibbott or e protein is one of the pathways but this ABP receptor pathway can also activate another kind of like structure here and what is it it can also activate GQ and if you guys remember GQ will stimulate a specific enzyme called phospholipase C phospholipase C does what it breaks down pip2 into ip3 and D AG ip3 does what it binds on to these receptors and triggers the release of calcium and calcium will then try to cause degranulation in class platelet aggregation and D AG again we know that this will activate protein kinase C and protein kinase C will also regulate the activity of the gp2 b3a so if you give clopidogrel prasugrel Tyco haggler Tecopa dean what's it gonna do it's gonna inhibit GQ right if you inhibit GQ you get less ip3 less calcium less degranulation less aggregation and platelet activation if you get less d AG you get less phosphorylation of the gp2 b3a which means less interaction between platelets awesome it's a beautiful mechanism right so we have aspirin we have clopidogrel pursue growth like a griller to Khloponin what else do we have what if we had something that directly bound and blocked these guys we do we do guys so what are these drugs that inhibit these their GP to be a3 inhibitors so things like AB 6 and mad tyro fivin an app to FIBA tied okay now these guys will do what they will inhibit the GP to be 3a interaction if there is no interaction between the GP to be a to p3 a proteins what's going to happen less platelet interaction and less stabilization of the clot that is a beautiful mechanism so you have your GP to be 3a inhibitors you have your ADP receptor inhibitors you have your cyclooxygenase inhibitor like aspirin there's actually one more remember this we haven't talked about this little tube yet this little jheri curl like enzyme and this enzyme is called PDE okay phosphodiesterase it's actually a tight it's a type 3 if we really want to be specific so it's called phosphodiesterase 3 and there is drugs that are utilized to inhibit that enzyme and what are some of these drugs well you have a drug which is called salats dissol okay we're gonna put them over here and why not bring an arrow to them okay so you have another drug called SCI lost us all and diaper animal and what these drugs can do is is they have the ability to inhibit this enzyme okay now let's explain why that's important what does phosphodiesterase is do they break down cyclic A&P and whenever cyclic AMP is broken down can it get converted into protein can activate protein kinase a No so if you inhibit this enzyme you inhibit the breakdown of cyclic a and P if you inhibit the breakdown of cyclic AMP P what does that mean you get increased cyclic AMP E which means you get increased protein kinase a which means you get increased phosphorylation of vas P which means that this is no longer going to be able to stimulate this protein and so now it's going to be in tremely inhibited so there's going to be extra inhibition that's so darn cool so that's one of the mechanisms of these guys so they have the ability to inhibit this guy they can also through other mechanisms inhibit these degranulation as well but one of the big things is they they inhibit this gp2 b3a alright so the last thing i want to talk about with the losses all and die pretty MO which is a really cool action of them and that's why they have another indication that we'll talk about a little bit afterwards called peripheral artery disease is they can also cause smooth muscle relaxation and blood vessels that's really important because it can dilate the blood vessel and increase the blood flow around any type of like maybe plaque or even thrombi so that's what's really cool about this drug so go ahead and take a look at how they actually do that so if you remember we have the endothelial lining here right and just underneath it you're gonna have that tunica media so if you guys remember your Anatomy you have Tunica interna which is basically simple squamous epithelial tissue with a little bit of loose areolar connective tissue underneath it then you have if you really want to be specific and internally elastic lamina after that then you have your tunica media which is a smooth muscle layer right what happens is selasa Zahl and diaper animal what did I tell you they do they inhibit this little jheri curl like pac-man and again that is what's really important because this is a P D e3 inhibitor right and this is a PD III enzyme so if you take some loss dissol and diaper it Amol and again inhibit this enzyme that's important so how does that work basically if you guys remember another thing for these particularly diaper animal is you have another molecule called adenosine an adenosine can actually bind onto these receptors they can activate a g-protein like G stimulatory protein which will then activate a dental aid cyclase adenylate cyclase when it's stimulated again we know that it takes ATP and converts it into cyclic A&P and cyclic AMP II then activates protein kinase a protein kinase a then acts on what's called myosin light-chain kinase and what's interesting is that whenever you take myosin light-chain kinase and phosphorylate it it's actually inhibited so in the phosphorylated form it's inhibited and so it's actually not going to be able to do what it's not going to be able to cause smooth muscle contraction so if we give a drug okay like selasa salt or diaper at a mall it's going to inhibit PB III that means that this enzyme is no longer going to be able to break down the cyclic AMP II right so that's gone so cyclic A&P production will start to rise protein kinase a production will start to rise increase phosphorylation of myosin light-chain kinase will increase and now the ability to cause smooth muscle contraction is inhibited so now what happens to this crossbridge formation there's not gonna be any phosphorylation of myosin there's not going to be any cocking and pulling or any of those reactions so because of that you get smooth muscle relaxation and that cool and that the smooth muscle relaxants what happens to the blood vessel it dilates so these kind of have like a little dual function they can inhibit platelet activation and aggregation as well as causing smooth muscle dilation so that is one of the beautiful things about these medications so there's a couple groups of medications that i want you guys to remember big one aspirin this is a really really important one okay second group is your antiplatelet medications particularly they call these themö pyridine derivatives okay don't worry about that I just want you to remember clopidogrel pursue 'grill Tyco haggler de clippety okay those are your adb receptor inhibitors your GP to be 3a inhibitors is ab 6mm Tyrel 5n and f2 v tide and the last one that i want you to remember which is your PD three inhibitors which helps to inhibit platelet activation as well as cause smooth muscle relaxation via vasodilation is selasa zahl and diaper animal okay so we covered their mechanism of action we covered what groups there and now let's talk about what we use them for all right guys so now that we talked about the mechanism of action and how it's basically designed to inhibit clot formation that's one of the big things is that it's thrombo embolic basically anti thromboembolic okay so we're trying to be able to prevent that so what are some different thromboembolic conditions that we have to protect these people from and that's why they should go in these medications well one of the big big big ones that you guys got to remember is acute coronary syndrome now if you guys remember acute coronary syndrome we can actually break down into three components right so we call it acute coronary syndrome or ACS we have unstable angina we have in STEMI and we have STEMI okay so unstable angina and stemming which is your non-st segment elevation myocardial infarction and STEMI which is your ST segment elevation myocardial infarction these medications are commonly utilized in ACS but more particularly a combo usually you're giving something like aspirin plus something like maybe clip it a grill or prasugrel or you're giving something like Tyco a girl or and in rare situations you might use something like a GP to b3a inhibitor specifically like AB 6m AB okay but really the only time where you're really going to want to use this one as if the patient has are extremely high risk so what I mean you might be used this to the patient's like greater than 75 so like okay well here we write down a couple reasons if they're greater than 75 if they're a diabetic if you see ST segment changes ST segment deviations on the EKG if you see really height rope levels if they have if you do an echo and their left ventricular ejection fraction is like less than 40 percent or if they have a lot of pulmonary edema okay then that would be reasons of why you want to use that six and that the reason why you don't give up six amount commonly for people who are going to be getting PCI because they have it acute in mine is because it has a very high bleeding risk okay you got to remember that the GP to be three inhibitors have the highest bleeding risk next thing how would I determine which one to use between clopidogrel pursue grow and Tyco haggler all right so with utilizing these medications and knowing which combinations to give to these patients whenever they're having an acute coronary syndrome it comes with kind of learning about the clinical scenario so and also their bleeding risk you got to remember their level of potency okay so when we talk about these starting with the most potent at one ab six a map is extremely potent as a high bleeding risk okay so all of your GP to b3 inhibitors are gonna be extremely potent the most potent the second one is going to be out of these pursue growth so it actually has a blackbox warning and you got to be careful because of its bleeding risk after that you have Tyco a girl or and then after that you have clopidogrel and some will even say that these are pretty much equal and in that ability but then the last one here which has the least amount of bleeding risk is aspirin so we have to realize here when we're talking about potency if you have someone in a cute coronary syndrome they're not extremely complicated other words not greater than 75 they're not a diabetic they don't have chest pain that's been lasting for more than twenty minutes they don't have any ST segment deviations the tropes aren't super elevated they're left ventricular ejection fraction isn't super low they don't have any pulmonary edema you don't really need to give up six in that okay well then what about the other ones pursued rule again you got to be careful whenever you're giving this medication it is a high bleeding risk so you're going to want to chance that now so we don't really do that one unless we absolutely need to it comes down to really complete Capital Grille and Tyco haggler these are kind of more commonly utilized ones okay tyke Aguilar is a little bit more effective and more utilize a little bit more just because there is the risk with clopidogrel of what's called TTP we'll talk about that also with Capital Grille another thing you have to be careful of is that there is certain individuals who are poor metabolizers so they have what's called a cyp2c19 mutation they're poor metabolizers of Capital Grille and in those situations pursue grow or tyke a grower would be the more likely option so ACS is going to be one indication and it's usually a combo what else well so again if someone has an acute coronary syndrome any of these things so any blockage so if they're having any type of thrombus which is including the myocardium this is going to be a good good and good drugs to give another thing that we want to remember is that these are usually medications that you can give pre and post ACS so you can give these medications both pre so we talked about giving these medications pre PCI so in other words before they go to the cath lab and they get angioplasty they balloon up the vessel and they're good post PCI okay and again it's usually a combo of aspirin and something else more likely than not it's aspirin and clopidogrel long term aspirin and Tyco a girl or for the pre PCI and then super needed situation aspirin in that six of Matt if needed pre PCI but usually post PCI a spring clip integral okay what about some type of CVA so certain situations where there's actually blood clots that are actually going to be going to different types of structures within the brain that could be another indication for givingness so again remember that cerebrovascular accidents this is also a good combo to give on things like aspirin and things like Klaipeda Grill another important thing here with CVS is sometimes if someone is getting a stent in the carotid artery so another thing to remember about is if someone's getting what's called carotid artery stenting you can actually give aspirin and clopidogrel you can give it pre and sometimes even post carotid artery stenosis okay so it helps with that process so if someone has a CVA or post CVA ask for a nickel pretty girl or good combinations to give if someone's getting carotid artery stenting where they're putting a little stint into the carotid artery it's also good to have these anti thrombotic agents as well okay another thing is if someone has already had an mi all right let's say that they have already had an mi they have heart failure something of that nature right there's also some risk sometimes so sometimes if someone has a already have been diagnosed with coronary artery disease okay so someone has already been diagnosed with coronary artery disease it's been shown that aspirin has the ability to reduce the significance of any other comorbidity so aspirin is also a really good indication for individuals with chronic coronary artery disease and it's just good prophylactic treatment so prophylaxis so basically preventing them from having another myocardial infarction or another CVA okay another really interesting indication for these medications specifically aspirin is in certain individuals who get what's called giant cell arteritis you know there's a vessel here called the temporal artery and what happens is the temporal artery it gives off some different branches so you have the Tim poor artery which can actually supply it parts of the forehead right the temples and but it also has these branches off the internal carotid artery called the ophthalmic artery and you also have vessels that are going to the muscles of mastication in certain situations people with giant cell arteritis if they have inflammation of those vessels they call it a vasculitis and you got to remember that vasculitis is a risk factor for developing clots and sometimes it can cause clots that develop within the ophthalmic artery or clots that develop within the vessels going to the mouth right to the jaw muscles and this can cause jaw claudication it can cause even vision loss and a lot of pain on the temporal region so a good medication that they give to individuals to prevent them from actually you know having some of these symptoms is aspirin so aspirin is another good medication that's utilized for peace by patients with giant cell arteritis so we have acute coronary syndrome whenever someone's having it in line and they're going to PCI post PCI we talked about that CVA same thing a spring clip integral whoo one thing I remember when because we don't give if people having a stroke within the first three to four and a half hours we don't give aspirin and clopidogrel it's after that time what do you give generally before the three to four and a half hours you give TPA so you got to remember that this for the CVA stuff it's actually particularly when it's greater than three to four and a half hours okay that's when you're really actually giving someone aspirin and clopidogrel combination so I want to make sure that we're perfectly clear on that okay giant cell arteritis again we talked about it syndication and if someone has diagnosis of coronary artery disease and it's a chronic condition you give them this aspirin to prophylactically prevent them from having another heart attack or having any other type of cardiac event okay another indication sometimes aspirin and clopidogrel can be used for PA D but remember there was a nice drug we talked about remember with PA D you have vessels here that run through the legs right okay and sometimes what can happen is they can actually develop plaques or thrombi or maybe different types of clots that can develop within these vessels and that includes the blood flow to the surrounding tissues it's like it's such as the muscles into the feet what can happen as a result of that you can get ulcers around that area of the body you can start getting a lot of what maybe even gangrene okay because you're not getting enough oxygen and nutrients to the tissues and so they start dying what else the muscles need oxygen order to contract so you can get tightness and pain within those muscles they call that claudication so this is common symptoms of someone who is struggling with what's called peripheral artery disease or PA D peripheral artery disease when we give medications we can give medications like aspirin so aspirin has a good medication to give to someone with peripheral artery disease but what else is another medication that we can give guys we already talked about its elasticity mall so I lost is also lost is always going to be a big one okay that is the more commonly utilized one so selasa is all and aspirin are good medications to give to patients with peripheral artery disease beautiful thing right what's super interesting and I found extremely interesting when I was actually doing some research is that aspirin has a prophylactic protection from colorectal cancer so whenever you're giving somebody aspirin they've shown that this can actually decrease the risk of colorectal cancer particularly a type of colorectal cancer called Lynch syndrome and if you guys know a little bit about Lynch syndrome it's basically a tumor that can actually form within multiple tumors that form with the multiple areas of the body like colorectal endometrial ovarian renal pancreatic so a lot of different things can happen with this and there's very different variants like Turco syndrome and Gardner syndrome so again they've shown that aspirin has the ability to decrease the risk of colorectal cancer significantly okay the last thing I'm going to talk about we're not gonna go into a ton of detail on it but diaper rhythm all remember I told you that it causes vasodilation right they use it as a specific test so I'm people who have maybe coronary artery disease and you want to diagnose it they do stress testing right so they do stress tests to see how good the perfusion is to the myocardium so you have them exercise well in certain individuals where they can't exercise for whatever reason they give them a drug called diaper animal and what diaper animal does is is it dilates the vessels going to the myocardium so that you can see the perfusion on the imaging techniques that you're utilizing but it increases the blood flow through the normal vessels but not very much through those actual fixed or stenotic vessels so that's why diaper animal is also good for stress testing if you wanted to remember that as well one of the big things with all these drugs is that some people say what about knowing the dosage is important but you know you can always look those things up and it's important to make sure that you do look those things up so that you don't make a mistake whenever you're giving someone the medications obviously knowing someone who is having some type of acute coronary syndrome is important to know that you should give them 325 milligrams of aspirin have them chew it and then swallow it but more for your daily prophylaxis it's more along the lines of like 81 milligrams per day clopidogrel the big thing that you should know dosage wise of this one is if you are giving it to someone who's going to be going to get a PCI or some type of carotid artery stenting or they have had a CVA that's been greater than this is the period of you know three to four and a half hours then you can give a loading dose of 300 milligrams and then from that point on you give them 75 milligrams every day but what I want you guys to remember is that these medications are basically designed to be able to prevent from what conditions or treat acute coronary syndromes CVAs outside of the range of receiving TPA people who are going to be getting carotid artery stenting or they're utilizing this basically as an adjunct to stenting CA D prophylaxis preventing them from having another myocardial event again aspirin for giant cell arteritis which is at a particular type of vasculitis pa D the good ones so losses all and decreases the risk of colorectal cancer significantly and again diaper at a mall it's used for specific types of cardiac stress tests to look at myocardial perfusion imaging alright so those are the indications of these medications alright guys so let's talk about the last two things here which is going to be the adverse drug reactions that can happen sometimes whenever you're taking these medications you got to be you know you got to watch out for as a clinician it's important for us to be able to recognize what is some normal side effects but what are the things that we don't want to miss so when you're putting people on these medications these antiplatelet medications there is a couple things that we do really have to be aware of and we have to watch out for so you have to think about these things one of the big things that you want to watch out for is you're putting some people on antiplatelet medications anti thrombotic medications you're trying to stop blood clots so sometimes if maybe you receive too much of the then you give them too much of the medication or they have some type of just severe adverse drug reaction where there are a rapid metabolizers of the drug they can have excessive bleeding and we want to watch out for that so what are some of the things that we could see that actually elude us - oh they might we might have them on too much of this medication we got to watch out we got to discontinue this medication so things like this would be bleeding bleeding from orifices are bleeding into the surfaces of tissues so one of the big ones that you got to watch out for is if someone is bleeding from their nose what do you call that epistaxis right so you want to watch out for what's called anterior epistaxis so that could be one type of indication it's letting you know oh they might have there might be bleeding too much and I need to discontinue this medication one is if they're bleeding from their gingiva from their gums so what if somebody shows signs of gingival bleeding so you start seeing bleeding from their gums okay that could be an indication so if you see gingival bleeding that could be an indication saying move they might be on too much of this medication we got to discontinue what if you see little pinpoint bleeding like little dots little pinpoint hemorrhaging little suckers on the skin what could that be indicative of they call this petechiae so if you see petechiae eye or you see very large types of heme pinpoint hemorrhaging that could be indicative of some type of purpura or maybe they're really large bruising and that could be ecchymosis so if you start seeing a lot of bruising on the skin petechia preparer ecchymosis that could be indicative or if there's blood that's actually coming out through their mouth hole right so if there's someone is actually vomiting up blood so if they have um if someone is having hematemesis right that could be an indication so someone's vomiting up blood or they're having Malena so they're having blood coming out through their stool maybe it's a dark type of blood and that could be indicative of an upper GI bleed or maybe it's bright red blood which is called hematochezia and that could be indicative of maybe a lower GI bleed so those are things that we want to watch out for okay another thing is that sometimes there could be excessive vaginal bleeding or uterine bleeding so we would want to watch out for any type of abnormal vaginal or uterine bleeding so these are some of the things that we want to be aware of when patients are on these medications look for any signs of bleeding sometimes you might not have any blood that's visible so what should you do if someone you think is on this medication they might be bleeding they have iron deficiency anemia whenever you take their a CBC go ahead and do a hemoccult okay so check to see if there is any blood inside of the stool as well again so whenever someone's on these medications do a very good physical exam look at their oral cavity look at their skin look just ask if they've had any recent nosebleeds ask if they've had any dark stools if they vomited up any blood do a hemoccult check a CBC ask if their periods have been heavy have they had any bleeding after sex anything like that is important to make sure that we look for that stuff the big thing that I really wants you guys to be aware of and you have to be careful of whenever you're putting someone on things like particularly clip integral and another one called tickle pitting that's why they don't use tickle budding as much anymore but clopidogrel you also have to be careful of with this one it's called TTP so you have to watch out for what's called T T P thrombotic thrombocytopenic purpura so what happens in this condition basically you have platelets right and what these platelets do is they're designed to be able to stick with the von Willebrand factor that's basically stuck in that collagen meshwork so let's go ahead and draw some von Willebrand factor molecules what happens is here's your von Willebrand factors here these little pink guys right now normally von Willebrand molecules are these little monomers they're just one little single protein but what can happen is they can actually start fusing with one another and this is a normal physiologic process where they confuse with one another and they can go from a monomer to a multi mer okay and you have a specific enzyme thank goodness that basically prevents this from happening and breaks these multimers down back into monomers okay and that enzyme is called atoms T 13 it's called atoms T 13 so this enzyme is designed to be able to stimulate the multi more break down into monomers that's important but in certain situations there might be a decrease of atoms T 13 what could be an indication of that what could be a reason antiplatelet medication such as clopidogrel to Khloponin it could even be a conditions like lupus or some sometimes a radiotherapy meta chemotherapy medications like gem try said threatenin Jen try Center beam cyclosporine some of those medications could also be reasons why there's a deficiency in this enzyme if that enzyme can't break down the multi mer into monomers what happens they just auto-populate and guess what they do guess what loves to stick to von Willebrand factor platelets and so then what do you get you'd get this huge platelet mess here and all these platelets start sticking to these multimers and what happens then the platelets start getting consumed but they start forming lots of clots so two things happen as a result of this you get a decrease in platelets they start getting consumed because you're making tons of clots so you're get an increase in clots because these multimers of von willebrand factor are binding tons of platelets and you're getting big clots but you're using so many of the platelets that you have a decrease in platelets so thrombocytopenia along with widespread clotting this is TTP and that's what you got to be careful of so what are some of the signs that if someone's coming in with you have to make sure that you recognize it and treat them accordingly if someone's coming in and have a fever okay so if they're fib Rao if anybody comes in and they're presenting with a fever that would be an indication okay maybe it's greater than 100 point 4 degrees Fahrenheit right or you get a CBC and on that CBC it shows signs of hemolytic anemia okay because again you're also within this process you're gonna start having red blood cells come through this area so there's also gonna be breakdown if your red blood cells hemolytic anemia so you'll be able to see that whenever you check because when the of these red blood cells are busted open you're get an increase in what's called LDH and enzyme inside of the red blood cell you get an increase in bilirubin which is a component of hemoglobin and there's another enzyme that loves to bind to hemoglobin and whenever hemoglobin is released onto the blood this enzyme once this protein binds to it and that's called half de globin so the amount of free haptoglobin will go down because it's bound to hemoglobin instead of free okay the other thing is you're using up your platelets so the platelets are going to decrease you're gonna thrombocytopenia another thing is that there's going to be damage to the kidneys so there can be renal insufficiency if there's kidney damage the ability to excrete out things like creatinine and a lot of blood urea nitrogen products decreases so what happens to that there's an increase in creatinine there's an increase in the bu n if you take and do a BMP and on top of that there's also certain types of neurological damage so they start might start experiencing things like headache they might have things like confusion okay and that's some of the things that we have to watch out for as well okay you can remember this through the montana monic that are in fat RN so fat RN you remember fever anemia thrombocytopenia renal insufficiency and neurological damage okay when someone has this what do you treat them with the best thing to do is to do what's called plasmapheresis okay and what plasmapheresis is is you're basically taking out all of these different types of structures that are in side of the blood and cleaning the blood okay so you're gonna do plasmapheresis they can also do what's called steroids cortical steroids and the reason why is we're trying to reduce the inflammatory response and sometimes they can use other medications like rituximab and again we'll talk about that in another video when we specifically go into it but right now if you notice it you got to treat it plasmapheresis steroids those are usually the main treatment contraindications to utilizing these medications there's a very very important one G you got to remember if the kid comes in the basically they say anything less than 19 years of age so less than 19 years of age the kid comes in less than 19 years of age and they have a fever you never give them aspirin okay you never give them aspirin and you want to make sure that the parents know that as well the reason why is and again the mechanism isn't completely like rock solid but this is what they think inside of your liver you have mitochondria right and the mitochondria are responsible for taking free fatty acids and breaking them down through a process called beta oxidation into what's called acetyl co a and then acetyl co a goes through the Krebs cycle and it generates some molecules like nadh fadh2 all these little suckers and that stimulates the electron transport chain to make ATP well what they know is is that there's two things one is when someone takes salicylates it's actually metabolized by specific enzymes in the actual mitochondria and their metabolites can actually affect this process of fatty acid oxidation so here's what I want you to remember so if someone is actually taking aspirin alright dope taking absorbed it has the ability to alter the metabolism of these free fatty acids so the metabolites so the metabolites of the aspirin has the ability to inhibit the free fatty acid oxidation process okay so that means what less acetyl co a less nadh less fadh2s and less ATP well guess what if someone is infected let's say that they have a virus okay let's say here we have a virus whenever someone is infected these viruses have the ability to increase the actual metabolism of these South's iliac salicylic acid metabolites so there's going to be more metabolites of aspirin whenever someone is having a viral infection so this virus has the ability to potentiate and increase the number of salicylic acid metabolites that means if you have increased salicylic acid metabolites you have increased inhibition of free fatty acid metabolism less acetyl co a metabolism less NADH is in left LS fadh2s and less ATP if you don't have ATP with inside of this cell what happens all the functions of the cell start to decrease in this cell will start to die its ability to perform its functions will decrease what is one of the big things that the liver does it filters out different types of toxins you know there's a process where you take amino acids and you rip off a specific molecule called ammonia and ammonia is supposed to go through a process inside of the mitochondria called the urea cycle okay well if the liver is failing are you gonna be able to metabolize that ammonia no what happens to the ammonia then it starts to increase in the bloodstream as ammonia levels increase in the bloodstream it actually moves its way into the central nervous system and affects little cool little cells here called astrocytes and it actually gets inside of the astrocytes okay and binds with a molecule called glutamate and turns into glutamine and this causes the astrocytes to become osmotically active and pull a lot of water into them and they start to swell what can this result in this can result in encephalopathy in cephalopoda which it will show up as signs as maybe vomiting then they can then progress maybe to fatigue and then maybe they'll progress from there into seizures and maybe even into a coma as well as till they can have delirium as well so when someone has a fever particularly maybe a viral infection they're less than 19 you give them aspirin you're gonna lead to this liver damage that liver damage will result of increased ammonia hyper M anemia which result in encephalopathy so what is the Triad you have a patient who has a febrile illness liver failure or liver damage how will you determine liver damage what's the markers whenever the livers damaged it releases ast alt all of these will be increased as well right so you'll have signs of liver damage you'll have vomiting fatigue seizures delirium coma signs of encephalopathy and a patient less than 19 years old with a fever what do they call this they call this Reye's syndrome so this is a contraindication you do not give somebody who is less than 19 with a febrile illness aspirin okay that's one of the contraindications another thing that we have to talk about really briefly here is what are some other reasons why you would not want to give someone some of these anti thrombotic agents what if they already have really low platelets so what if their platelets are extremely low especially one of the big ones is AB 6 map your GP to be 3a inhibitors they really can drop down your platelets so if someone has less than a hundred thousand platelets you do not give them GP to b3 inhibitors so it can cause thrombocytopenia so you don't want to give someone these drugs if they are extremely thrombocytopenic especially like less than 100,000 platelets per centimeter cubed of blood millimeter cubed sorry another reason what if someone has uncontrollable hypertension so their their actual blood pressure their systolic blood pressure is extremely high that's one reason another reason why is is because with high blood pressure there's risks of tearing through that Tunica intima layer and whenever you do that what can that cause that can cause a ordered dissections so then with this happening if someone has uncontrolled hypertension and they have a ordered dissection a history of aortic dissection they're at high risk of bleeding if you give them any of these medications so be careful if someone has a history of an aortic dissection or they have uncontrollable high blood pressure well that's another reason why you wouldn't to give this if they're already bleeding if someone has maybe a perforated peptic ulcer so what if they have a perforated peptic ulcer or some type of GI bleed all right so this could be a problem if someone is having a GI bleed whether it be an upper GI bleed or be a lower GI bleed or if someone's having an intracranial bleed so if someone's having some type of particularly maybe like a subarachnoid hemorrhage you don't want to give them that medication or if there's some type of trauma so maybe they were stabbed or maybe they went under the knife for some type of really intense surgery that's another indication of where you're not gonna want to give this medication all right so that should cover all of the things that we should need to know about antiplatelet medications I engineers in this video we talked about antiplatelet medications I hope it made sense I hoped you guys did enjoy it if you guys did please hit that like button comment down in the comments section please subscribe also as a reminder please go check out the great courses plus again you can go down in the description box or it's the great courses plus comm slash an engineered science they have a lot to offer and it can definitely further your knowledge of multiple different topics so go check that out as always ninja nerds we love you and until next time [Music]

Channel: Ninja Nerd

Views: 102,577

Rating: 4.9684625 out of 5

Keywords: ninja nerd science, antiplatelet medications, antiplatelets, anticoagulants, pharmacology

Id: 1L5ztliNLMc

Length: 57min 32sec (3452 seconds)

Published: Thu Jan 02 2020