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How do Direct Thrombin Inhibitors Work? (Dabigatran)

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How do Direct Thrombin inhibitors (Dabigatran) Work? These direct thrombin inhibitors are anticoagulants that block clotting factor 2 which prevent the production of fibirin. This causes a decrease in blood clots and ultimately “thins” the blood.

Welcome to another drug chug episode and today we’re gonna talk about direct thrombin inhibitors like the bigot ran and how they work in this video we’ll talk about everything you need to know about these direct thrombin inhibitors so let’s get into it so here’s a quick breakdown of everything in this video there’ll be timestamps down below and at the end we’ll

Have a short quiz to see what we retained okay to first understand this class of drugs we need a quick overview so the direct thrombin inhibitors you need to know that they’re anticoagulants and that just means they stop and prevent blood clots from forming in the body now there are two main direct thrombin inhibitors and here we have the bigoted ran which is

Brand-name pradaxa and then we have something called our gautreaux ban which actually doesn’t have a brand name and it’s actually an injection with the injection side there’s also three other ones called leper rudin dessa rudin and the vala rudin but i only want to focus on the bigger tran and our gat rabanne because those are the ones you’ll most likely see so

If we take a look at the bigger trend what’s unique about too big a tran is that it comes in oral capsules so we could dispense this to patients so that they could just take it orally now because of that it’s also referred to as a dou ak or a direct oral anticoagulant and this is also true with the factor 10a inhibitors we talked about in the previous episode if

You’re following the course now on the right side these are all injections right so the arghast rabanne left peru donessa rudin pahlavi rudin they’re all infusions and although they’re not oral we still refer to these as direct thrombin inhibitors because they all work the same way the only difference is that the bigger tran you could take orally everything else has

To be an infusion so as a quick overview all of these drugs are anticoagulants because they stop or prevent blood clots but out of them only one is oral and the others are infusion now that we’ve had a quick overview let’s go a step deeper and figure out how these direct thrombin inhibitors actually work let’s see what their mechanism of action is and to do that

We need to talk about the clotting cascade because we’re talking about blood clots and all the clotting cascade does is if you have a paper cut or you’re bleeding all it does is it makes you not bleed and it’s very complicated and we’ve gone through the several times so i’m going to give a quick overview and essentially what happens is you have a bunch of clotting

Factors and you have the intrinsic pathway which is damaged on the inside and you have the extrinsic pathway which is having damage on the outside and all these clotting factors activate each other until we hit the middle which is the median pathway and here we have clotting factor ten that activates clotting factor two and then activates clotting factor one it’s

Important to know that clotting factor one is the whole point of a clotting cascade because clotting factor one is fibrin and we need fibrin to make blood clots so here blood clots equal platelets which are circulating in our blood plus fibrin so where does the bigot ran really work well clotting factor 2 is also known as thrombin and earlier we said these drugs

Are direct thrombin inhibitors so if we have a patient like this one here and we dispense them the bigger trend and they take it essentially what happens is the bigot ran will block clotting factor 2 also known as thrombin which will eventually lead to blocking fibrin and then if we block fibrin we block blood clots and that’s exactly how this drug works all right

So now that we know how the bigot ran and these other direct thrombin inhibitors work let’s talk about when actually use them if a patient has atrial fibrillation meaning that atria or the top part of a heart isn’t pumping correctly this could lead to poor blood circulation if there’s poor blood circulation and that blood stays in the same area it could lead to

A blood clot now this is specifically for a non valvular a-fib so if a patient has a prosthetic valve implanted we can’t use the bigger tran we’d have to look for other products like warford we could also use it if a patient has a deep vein thrombosis so this is a blood clot usually happening in the deep veins like in the leg and we actually have two uses we could

Either have a prophylaxis dose meaning they don’t have the deep vein thrombosis yet but they’re at risk or they currently have the deep vein thrombosis at this time and we need to treat it the same thing is true for a pulmonary embolism so this is a blood clot traveling to the lungs and this is a very serious condition and same thing we have a prophylaxis dose

Meaning they don’t have it yet but they’re at risk or a treatment dose meaning they have the blood clot right now and we need to treat them right now we could also use these drugs after surgery so if a patient has a knee replacement surgery or a hip replacement surgery we could prescribe them these drugs so that as they’re recovering a blood clot doesn’t occur

Because of the stress a surgery could have on a body now there’s one unique thing i want to talk about here and it’s heparin induced thrombocytopenia which means if a patient was on heparin and heparins usually used during surgery they have this condition where the body attacks the platelets it’s complicated but essentially it’s kind of like an autoimmune disease

Temporarily and the body is just constantly attacking the platelets so what happens is the platelets drop down and the patient is in critical health they could bleed out like crazy so to prevent this we actually use our gastro ban so if the patient has hit or heparin-induced thrombocytopenia typically the go-to is our ghat rabanne so now that we know when to use

These drugs let’s talk about the dosing a little bit so let’s start with the bigot ran and the brand name is pradaxa and here we have to be mindful of creatinine clearance so we have to know how well our patient’s kidneys are working so for dabigatran if a patient has a fib it’s real easy we give them a hundred and fifty milligram capsules twice a day if they have

A deep vein thrombosis or pulmonary embolism same thing we give them a hundred and fifty milligrams capsules twice a day now if we want to do prophylaxis of a dvt meaning they don’t have a blood clot but they’re at risk let’s say it’s after surgery then we drop them down to a hundred and ten milligrams within the first four hours after surgery and then we give

Them two hundred and twenty milligrams once daily for the next ten to fourteen days depending on the type of surgery now we said that the kidney function is important so if a patient’s creatinine clearance is more than 50 milliliters per minute you don’t need to worry there’s no adjustment now if the creatinine clearance is between 15 and 30 we have to drop it

Down so instead of 150 milligrams twice a day it drops down to 75 milligrams twice a day so the dosing is not too bad so now when we look at our gat rabanne it’s a little different this is weight-based dosing and remember we use this for heparin induced thrombocytopenia and the way it works is we have an initial dose of two micrograms per kilogram per minute and

It’s a continuous infusion and essentially we’re monitoring the patient to see their platelets come back up and then we adjust accordingly okay so now that we know how these drugs work when we use them let’s talk about some clinical pearls and side-effects so the first one here is there are no routine blood tests which is a good thing unlike warfarin where you

Have to check the inr every week to every four weeks the bigger tran and these other direct thrombin inhibitors don’t need routine labs the next thing here is it works fast it works on thrombin specifically the activated form of thrombin so we don’t have a delay just like how we saw in warfarin that there was a delay here there is not then we see kidney function

Plays a role in our dosing usually under 50 creatinine clearance is when we would take a look at adjusting the dose and then with all our anticoagulants we know there’s a bleeding risk if we give a patient too much we could push him to bleed more and that’s something we don’t want now a dabigatran there are three big things you need to know and this is high yield

Information and we said the bigger trend was our only oral direct thrombin inhibitor the first thing is that it’s a very large pill and it’s actually hard to swallow and the issue is that you can’t crush this pill at all because it’ll damage the drug so think about if a patient has a stroke a blood clot and it’s hard for them to eat or drink already it might be hard

For them to take this medication twice a day especially since it’s so large the second thing here is that you’re not allowed to use a pill box to organize your medication a lot of patients that have many medications on board will use a pill box to stay organized but the problem with the bigger tran is that the medication needs to stay in the original container

Or blister pack and the reason is that this vial has a special desiccant that’s built in to absorb all the moisture so that the drug doesn’t degrade or break down even in the original container this drug expiration dates only four months so we have to be very cognizant and look at these drugs and not let them expire because they’re very sensitive to moisture and

The last thing here is that it has an antidote the antidotes name is prax mind and then the generic is a monoclonal antibody and it works only with the big a tran and it works fast all right we made it to the end so let’s have a quick summary of everything we learned so we talked about all our direct thrombin inhibitors we had the bigot ran our gat rabanne leper

Udan desa rudin and ville valo rudin but we only focused on the the bigot ran in our gat rabanne out of all of these only this one here has an antidote and that was a dabigatran and the name of that antidote was practice bind so then we talked about how these direct thrombin inhibitors worked and we talked about the clotting cascade and we talked about how these

Clotting factors activate each other so we said that clotting factor 10 activates clotting factor 2 which then activates clotting factor 1 which is fibrin and then we know that blood clots are made out of platelets and fibrin so when a patient takes a drug we block the clotting factor 2 which is also known as thrombin which blocks fibrin which blocks fibrin in the

Making of blood clots lowering the blood clot creation so now that we know how it worked we talked about when we actually use them if a patient has a fib a dvt apollinaire embolism or after surgery and then we also talked about our gotcha ban specifically if a patient has heparin induced thrombocytopenia and that was when a patient was on heparin during a procedure

And essentially the body attacks the platelets making them dangerously low then we focused on the bigger trend because that was our only oral direct thrombin inhibitor and then we had a few caveats here we said that it was a very large pill that you can’t open crush we also said you can’t put it in a pill box because it’s got to remain in its original container

And then again we said this is the only one that had an antidote and that’s it so let’s take a short quiz to see what we retain all right question 1 which of the following comes in an oral dosage form question two which clotting factor does the bigot ran block question 3 what is the dosing to treat a fib with the bigoted red question 4 what is the name of the

Antidote used to reverse the bigoted ram

Transcribed from video
How do Direct Thrombin Inhibitors Work? (Dabigatran) By Drug Chug