How Does Clopidogrel (Anti-platelets) Work? (+ Pharmacology)

hello and welcome to another drug Chuck episode and today we'll be talking about anti platelets like clip hitter grill and how they work plus some pharmacology so let's get right into it so a quick breakdown of everything in this video first we'll talk about how platelets actually work then we'll talk about the ADP p2 y12 antagonists like clopidogrel and the mechanism of action then we'll get into the thigh no paradigms versus the non thigh or no paradigms and high platelets then we'll talk about the drugs in detail like the dose and indications then the side effects and then a quick summary and then as always at the end we'll have a short quiz to see what we retained so a quick overview just so we're all on the same page anti thrombotic SAR also known as blood thinners because essentially we're thinning the blood and they're broken down into three sections so these are the three categories of drugs we could have that we can have anti platelets like clopidogrel we could have anticoagulants and thrombolytics and here we're gonna focus on anti platelets and this category breaks down into several others such as cox-1 inhibitor which is our aspirin our PD III inhibitors our ADP p2 y 12 receptor antagonists and this is clip integral and other drugs in that class which we'll focus on in this video glycoprotein 2 B 3 a receptor antagonists and thrombin receptor antagonists but again we're gonna be focusing on this adp receptor antagonist section so to know how these anti platelets work specifically clip it oh girl and the ADP P 2 y 12 receptor antagonists we need to know how platelets work in general so here we have a calm platelet and the completely it usually just circulates our blood stream and doesn't really do anything until we get a cut or damage in our vascular tissue and that completely senses the damage and becomes a angry platelet now at this point we have platelet recruitment and aggregation which just means more and more platelets are coming together and the cell mediator or the signal for the cells to recruit and aggregate is thromboxane a2 and ADP now if you remember we're talking about clopidogrel in this video and clip integral is a adp receptor antagonist just to keep that in mind once these platelets are recruited together they form a platelet plug now while this is happening we also have something called the coagulation cascade which essentially forms something called fibrin which is basically a fiber and the fibrin actually binds the platelets together to form a more consolidated fibrin clot so this is an even stronger blood clot than just the platelets alone and this is how platelets work they bind together and specifically thromboxane a2 and adp cause this binding together of the platelet plug so if a patient has a risk of forming blood clots one of the things we could do is reduce that ADP molecule from binding on the receptor so that way we prevent blood clots from occurring and we'll look at that in a little bit more detail on how that actually works all right so let's take a look at the adp receptor because we just said that the ADP molecule causes more and more platelets to recruit and aggregate to become a platelet plot some of this may look confusing but I promise you it's not right now we're looking at the surface of a platelet and here we have that p2y adp receptor and our drugs are gonna block this receptor and if we block this receptor we allow this enzyme called adenylyl cyclase to work and because we're allowing it to work it makes ATP break down into cyclic a.m. P and the cyclic a.m. P causes an increase in PKA now when you have an increase in PKA it controls the platelets and it causes a decrease in platelet aggregation so long story short what to take from this is that when ATP is blocked we have less platelets now that we know blocking the adp receptor stops the platelets from recruiting and aggregating what's the point of actually blocking platelets well if we have over activation of these platelets they could produce something called a thrombus and a thrombus is basically an unwanted blood clot and these unwanted blood clots can cause serious damage and even death in a lot of patients if this thrombus breaks off and floats in the blood it's called an embolus and this embolus can reach our brain and cause a stroke because it's stopping the blood supply to the brain now if that embolus goes to the heart it can block the coronary blood vessels and cause a heart attack because your heart's not going to get blood or if it goes through the heart it could get to the lungs and when it's in the lungs we call that a pulmonary embolism and this is one of the most severe and life-threatening blood clots that a patient could get because there's a high percentage of sudden death when you have a blood clot traveling to the lungs so as you can see it's a very serious and dangerous disease State and we need to have patients on anti platelets to prevent any of these complications now not every patient has to be on antiplatelet or anticoagulant therapy but if our patient has had a stroke or a heart attack in the past there's a good chance that they may have in the future and that's when we use these drugs to prevent a secondary occurrence or if the patient is at high risk because let's say they're going through chemotherapy if they have cancer we put patients on these drugs to prevent a blood clot from forming so when using antiplatelet therapy specifically the adp receptor antagonists we can break them down into two separate groups we have something called the cyano pyridines and the non sino pyridines so starting on the left hand side we have the thionyl para Dean's and þÿÿÿ no just means that there's a sulfur in the Rings and it's a parroting group and the reason why I bring this up is because if we have a sulfur we usually think about allergic rashes that happen in patients also if you could remember the thigh no parroting drugs that sulfur group has a covalent bond which basically means it's a very strong bond and it's an irreversible inhibitor now the three drugs on this list is going to be tickle oppa Dean which is tickling clopidogrel which is plavix and prasugrel which is eviant but we'll get into the detail of these drugs on the next slide on the right side we have the non final pyridines which suggests that there is no sulfur group and it's a nucleoside analog meaning it's a natural nucleoside that we have in our body and because of this we have a reversible bond which means we have a faster onset of action and the two drugs here we have two Kaggle or which is Berlinda or kangaroo lore or cane grill now keep in mind both of these subsets of drugs do the same exact thing they block the adp receptor causing a decrease in platelet activation all right so let's get into the drugs so first we'll talk about the thionyl pyridines remember there's a sulfur group that's why there's the word þÿÿÿ no and because of that they're irreversible and they could also cause allergic rashes now the first drug on the market was to Khloponin which is tick lit now typically we will not see this on the market if you're in the united states they may still use this outside of the country and the dose used to be 250 milligrams by mouth twice a day with food again this was the first drug to market it could cause that rash and it's not popular anymore because of the other drugs that we'll get into now the drug that kind of took over was clopidogrel or plavix here we see the dose to be 75 milligrams by mouth daily keep in mind there could be a loading dose of 300 milligrams but it's not always constituted so more information we know it's the most popular but very very important high-yield information is that the patient must have sip to see 19:00 activity because this drug is a pro drug and it will not get activated if they don't have sip to see 19 you also have to watch out for drug drug interactions so any drugs that inhibit or induce sub 2 c 19 will have a contraindication with clopidogrel so very high yield information clopidogrel you must watch out for the sip to see 19 enzymes in the liver so that it could activate the drug so when do we use these antiplatelet medications well we've talked about this before if they've had a heart attack or stroke or they're at a high risk of developing a heart attack or stroke they could be on this medication or if a patient has peripheral artery disease which is basically instead of a blood clot blocking the blood flow it's fat and lipids that build up over time in the veins that stop blood flow so they could also benefit from this antiplatelet therapy now the last final pyridine antiplatelet drug is progres which is brand-name Afyon and here we have a loading dose of 60 milligrams by mouth and then a 10 milligram daily dose for maintenance some important information for prasugrel is that it's the most potent and you have to be very cautious and patients that weigh less than 60 kilograms and you only use this medication with patients that have something called a percutaneous coronary intervention it's a long fancy word for having a stent and a stent is just that metal brace that opens up the blood vessel so that blood can flow through so prasugrel is only in patients with stents and those are our three sino Paradine antiplatelet drugs now let's talk about the non thionyl pyridines and here we only have two drugs so first let's start with Takai girl or which is brand-name bRILINTA and here the dosing starts with at a hundred and eighty milligrams as a loading dose and then we drop it down to a ninety milligram dose twice a day for a year and then we drop it down to 60 milligrams by mouth twice a day so some information a very important fact to know is that you do not exceed aspirin a hundred milligrams a day because then it antagonizes the effect of Takagi lor you can't use both of them if you're using aspirin more than a hundred milligrams a day and you can use with or without stents so remember before we talked about prasugrel being with stents to Kaggle or can also be used with stents now some unique side effects for take a girl or is that you could see ventricular pause in patients where their ventricular contracting stay contracted for more than three seconds we may see gynecomastia which is breast development in men or dyspnea which is just a term for shortness of breath and now our final adp receptor antagonist drug is gangrel or or brand-name can grill and here this is IV only so the dosing is 30 micrograms per kilogram IV bolus immediately and then you follow it with a continuous infusion at four micrograms per kilogram per minute now Kangra lor is only used during surgery and the onsets two minutes so it's the fastest onset out of all of these antiplatelet drugs so now let's go over some of the common side effects that we might see when we use a DP receptor antagonists or any anti platelets and the first thing we might see is bleeding and that makes sense because we're stopping the natural clotting of blood by stopping the platelet activation and if we do this too much we might see anything from a common nosebleed all the way up to a blood hemorrhage in our brain the next thing we might see is bruising because we're not allowing our blood to clot or fix itself if there's an internal damage that might cause easy bruising or an internal bleed and the last thing we may see is dyspepsia which is just basically your stomach not handling the drug too well and you have some discomfort so these side effects can range anywhere from being very serious to very minor all right let's have a quick recap of everything we learned so here we have our calm platelets and we know these calm platelets circulate our blood and then once we have a finger cut or some sort of damage they sense it and they become activated as mad platelets these mad platelets then react to thromboxane a2 and ADP and once it senses the thromboxane a2 and ADP it causes them to aggregate even more making a platelet plug but we now know that we have a DP receptor antagonists like clopidogrel that block ADP so when we block the ADP receptor we let adenylyl cyclase do its thing and it breaks down ATP to cyclic AMP E which increases the PKA concentration which then controls and decreases the platelets so then we talked about the five drugs in this class we started with the thigh no pyridines which have that sulfur group that makes them irreversible and can also cause a rash the first one we talked about was to Claude a pain brand name tick lid and this isn't on the market anymore then we talked about clip hitta grill or plavix which kind of took over but it's a prodrug and requires sip to see 19 for it to activate and we also talked about prasugrel or fvn then we went into the non final pyridines or the nucleoside analogues and here we only had two drugs and we talked about two Kaggle or which is brand name bRILINTA and Qing rule or or King grill which is only used in surgery and that's everything so let's get into the short quiz to see what we retain so question 1 which of the following is true for the ADP p2i receptor antagonists question two which of the following is a non final pyridine adp p2y receptor antagonist question 3 what is the maximum amount of aspirin a patient can take while on bRILINTA question for which ADP p2y antagonist is used as an IV route during surgeries [Music]

Channel: Drug Chug

Views: 66,587

Keywords: clopidogrel, clopidogrel mechanism of action, clopidogrel pharmacology, Plavix, p2y12 inhibitors mechanism of action, p2y12 inhibitors, p2y12 receptor inhibitor, How does Clopidogrel work, antiplatelet drugs, antiplatelet drugs mechanism of action, antiplatelet pharmacology, ADP rece, usmle, NAPLEX, antiplatelet drugs pharmacology, pharmacology made easy, How does plavix work, how do p2y12 inhibitors work, prasugrel mechanism of action, ticagrelor mechanism of action, Drug Chug

Id: t1VePRKHUxo

Length: 18min 0sec (1080 seconds)

Published: Thu Dec 26 2019