Lectures

Antiplatelets

by Pravin Shukle, MD
(1)

Questions about the lecture
My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides PharmacologyOfBloodCoagulation.pdf
    • PDF
      Download Lecture Overview
    Report mistake
    Transcript

    00:01 Let's start off with looking at a platelet. So, a platelet is a very important part of a blood clot, it's like the brick in the wall. And platelets, if they don't adhere to each other, aren't going to form very good clots for us.

    00:14 So the glycoprotein IIb/IIIa molecule is central to the function of a platelet.

    00:20 You can see here, I have a picture of a platelet next to me. And you can see in blue, the glycoprotein IIb/IIIa molecule which is also called the alpha IIb beta 3 molecule in Europe allows that platelet to adhere to the collagen substrate of any particular tissue.

    00:38 The other thing that this glycoprotein IIb/IIIa molecule allows us to do is adhere to other platelets so you can see that there is another platelet attaching to the first platelet through fibronogen.

    00:49 This cross linking and activation of platelet adhesion and aggregation are important components of the glycoprotein IIb/IIIa molecule.

    00:58 The third component of platelet function is its release function.

    01:03 Now, thromboxane A2 place a very important component in the release function.

    01:07 ADP is released when platelets bind to damaged tissue. And ADP is another important component in platelet function.

    01:15 This brings us to our first drug, aspirin. Aspirin is an irreversible inhibitor of cylooxygenase.

    01:23 It is used to manufacture thromboxane A2. And platelets, when you inhibit cyclooxygenase with aspirin, actually are permanently inhibited. That means that the antiplatelet function of aspirin is going to last for the entire life of this platelet, and that means that only replacement platelets will be functional, and that means that the aspirin is going to last anywhere between 3 and 7 days.

    01:48 Interactions of aspirin are very important because the aspirin is going to interact with non-steroidal anti-inflammatory pain agents. They impair platelet functions on their own and when combined with aspirin, you actually have an enhanced antiplatelet effect.

    02:07 The next group of drugs that I want to talk about are the glycoprotein IIb/IIIa inhibitors.

    02:12 We've already spoken about GP IIb/IIIa before, and we've illustrated how important it is in platelet adhesion and aggregation.

    02:21 So, we have reduced adhesion with the IIb/IIIa inhibitors, and we have reduced platelet aggregation.

    02:27 These are the drugs that are commonly used in this drug class. You don't need to know them so much as you need to know that they are used in the cath lab to inhibit platelet aggregation after catheterization.

    02:39 The ADP inhibitors are another drug class. You need to know this for your exam, so pay close attention okay.

    02:46 Clopidogrel and prasugrel are the two drugs that we are using right now in clinical practice.

    02:52 They require hepatic conversion to be active so they don't act right away, they take some time to actually work.

    02:58 They are also irreversibly inhibitive of platelet function.

    03:04 There are some new drugs that have come out. Ticagrelor or Brilanta is a very commonly used drug in the cath lab, it does not require hepatic activation, and it is a reversible inhibitor of ADP receptors.

    03:17 So, ticagrelor is a reversible inhibitor, clopidogrel and prasugrel are not reversible, they are irreversible drugs.

    03:27 It's really important. I want you to remember the distinction between the two because guaranteed I'm going to put it on an exam.

    03:35 Let's talk about the next class of drugs. Dipyridamole is a very commonly used agent that has a dual mechanism of action.

    03:43 The first action is that it inhibits phosphodiesterase. That reduces cyclic AMP mediated degradation and cyclic AMP is an inhibitor of platelet aggregation. So, there is a double negative there, pay attention, more cyclic AMP means less platelet aggregation. So in other words, these drugs inhibit platelet aggregation.

    04:05 The second effect of this class of drugs is that it inhibits the uptake of adenosine.

    04:09 So it increases your plasma concentration of adenosine. Adenosine acts through that A2 receptor on the platelet surface And the A2 receptor activation causes increases in plasma cyclic AMP levels.

    04:22 Once again, more cyclic AMP means less platelet aggregation, so we have less platelet aggregation through adenosine mediated action.

    04:31 So, this brings us to the actual uses in clinical practice. Aspirin is the most commonly used antiplatelet that we have.

    04:39 It reduces heart attacks. An aspirin a day, keep the cardiologist away.

    04:44 It also reduces stroke. So we use it all the time in preventing stroke activity. And it reduces peripheral arterial ischemia.

    04:51 So the three areas are heart, brain, and the legs, or peripheral arterial supply.

    04:57 The direct inhibitors also prevent restenosis after angioplasty. It's used in acute coronary syndrome.

    05:06 We spoke about clopidogrel. Remember that it's an irreversible inhibitor, it prevents TIA's with many strokes.

    05:13 It prevents strokes. And it reduces restenosis of stents. So a lot of time, we will use clopidogrel or prasugrel for about a year after we put in a drug eluting stent.

    05:25 Dipyridamole is often used in combination. We sometimes use it as an adjunct to warfarin in patients who have artificial mechanical heart valves, and we use it in combination with aspirin for secondary prevention of stroke.

    05:39 So, the thing that you want to remember is that if a person has a stroke, we give them aspirin, if a person on aspirin has a stroke, we give them aspirin plus dipyridamole or we switch them to one of the other drugs.

    05:52 And finally, there is a new drug that's out on the market that is used to treat intermittent claudication.

    05:59 In terms of the toxicity in these drugs, they are not insignificant. So, aspirin has a bleeding rate of about 0.3 %, or 3 per 1000. Ticlopidine has a bleeding rate of about 5 %, but a 1 % rate of severe neutropenia.

    06:18 Ticlopidine is a drug that you only need to know because we don't use it anymore.

    06:23 So, thrombocytopenic thrombotic purpura is a rare complication, severe neutropenia is a common complication at 1 %.

    06:31 On your exams, they are going to talk about the side effects of this drug, but in real world clinical practice, we don't use this drug anymore.

    06:40 We spoke a bit about the direct inhibitors, the side effects of course are bleeding and thrombocytopenia with chronic use.

    06:47 We only use this drug short term, so it's not as much of an issue with it.

    06:52 Clopidogrel, the bleeding rate is less than 1 %. It is certainly present, and when you combine clopidogrel and aspirin together, the bleeding rate increases.

    07:04 Dipyridamole is that agent of drug that we were talking about.

    07:08 It adds between 1 and 2 % bleeding risk to your drug that already has a bleeding risk.

    07:14 And then in terms of the peripheral drugs, they are contraindicated in heart failure.

    07:20 This is going to be on your exams, know this. This particular drug, it is contraindicated in heart failure.


    About the Lecture

    The lecture Antiplatelets by Pravin Shukle, MD is from the course Pharmacology of Blood Coagulation. It contains the following chapters:

    • Antiplatelets: Looking at a Platelet
    • Antiplatelets: Aspirin
    • Antiplatelets: Glycoprotein Inhibitors
    • Antiplatelets: ADP Inhibitors
    • Antiplatelets: PDE/Adenosine Uptake Inhibitors
    • Antiplatelets: Uses
    • Antiplatelets: Toxicity

    Included Quiz Questions

    1. ADP
    2. GPIIb/IIIa
    3. Alpha granule
    4. Dense granule
    5. Fibrinogen
    1. Cilostazol
    2. Dipyridamole
    3. Aspirin
    4. Eptifibatide
    5. Clopidogrel
    1. Eptifibatide
    2. Clopidogrel
    3. All of the answers are irreversible.
    4. Aspirin
    5. Prasugrel
    1. All of the answers would be expected.
    2. Increase in platelet cAMP levels.
    3. Inhibition of phosphodiesterase.
    4. Increased activation of A2 receptor on platelet surface.
    5. Increase in plasma concentration of adenosine.

    Author of lecture Antiplatelets

     Pravin Shukle, MD

    Pravin Shukle, MD


    Customer reviews

    (1)
    5,0 of 5 stars
    5 Stars
    5
    4 Stars
    0
    3 Stars
    0
    2 Stars
    0
    1  Star
    0