Transcription
Hey guys, it's Medicosis Perfection Ellis, continuing our series about bleeding and coagulation disorders. In the previous video, we had a comparison between GP Ib and GP IIb/IIIa. Today, I'll talk about the famous anti-platelet, analgesic, antipyretic, and anti-inflammatory wonder drug, also known as ester salicylic acid. With that being said, now let's get started. [Music]
Acetylsalicylic acid, aka the wonder drug. I wandered lonely as a cloud that floats on high o'er vales and hills, when all at once I saw a crowd, a host of golden daffodils beside the lake, beneath the trees, fluttering and dancing in the breeze. William Wordsworth. We don't write good English anymore; we're in trouble, dear William. You're worth more than your words.
Acetylsalicylic acid, aka aspirin, aka the wonder drug, is antiplatelet, analgesic, antipyretic, and anti-inflammatory. One of the non-steroidal anti-inflammatory drugs, although we like to classify non-steroidals into aspirin and other non-steroidal anti-inflammatory drugs because aspirin's connie unique comes from the willow tree. And if you check my video called "A Brief History of Hematology," I've talked about the history of aspirin and the willow tree and Bayer AG, the pharmaceutical corporation. Why, by the way, what's the difference between aspirin and Aspirin? Aspirin (small a) is a generic drug; Aspirin (big A) is a trademark for the company Bayer AG. So if you decided in the future that you would like to launch a company to produce aspirin, you can do it; it's perfectly okay. However, when you write aspirin on your bottles, you have to write a small a, not big A, because big A is a trademark for Bayer. You don't mess with our trademark, okay? You don't mess with Texas. Out the bear or German, they are not from Texas, but anyways…
Mechanism of action of aspirin: irreversibly inhibits the cyclooxygenase. How does it inhibit? By acetylation. It's called acetylsalicylic acid, for heaven's sake. When you inhibit the cyclooxygenase, you don't get any thromboxane A2, so there is no platelet aggregation. This is called irreversible non-competitive antagonism of cyclooxygenase. Irreversible means you cannot go back. Non-competitive antagonism, which means you cannot add another drug to compete with aspirin at the same receptor; it's not gonna happen. It's uncompetitive. After taking the last aspirin pill, how long do you have to wait until platelets restored their function? You have to wait 48 hours. You have to wait for the old platelets that have their cyclooxygenase inhibited to die and for the bone marrow to release megakaryocytes to be destroyed into platelets. The new platelets have normal cyclooxygenase; they can produce thromboxane A2 and you can function normally again.
Question: Does aspirin inhibit cyclooxygenase-1 or cyclooxygenase-2? And the answer is both. Aspirin inhibits both cyclooxygenase-1, cyclooxygenase-2. How about prostaglandin I2, prostacyclin? Aspirin doesn't inhibit it. It's gonna be more sophisticated, okay? In the beginning, it inhibits prostacyclin, but at the end of the day, there is no inhibition because the receptor is whatever I'm being accustomed to the aspirin, blah blah blah. I don't care. Membrane phospholipid into arachidonic acid, cyclooxygenase, you have the prostaglandins, thromboxanes. You have the look with trying prostaglandin G2, prostaglandin H2, depending on this, you have thromboxane A2. Prostaglandin I2, also known as prostacyclin. Thromboxane A2 is pro-coagulation; prostacyclin is anticoagulation. Aspirin inhibits the pro-coagulation; that's why aspirin is anti-platelet. That's why if you take lots of aspirin, you'll bleed.
Is aspirin anti-platelet because it inhibits cyclooxygenase-1 or cyclooxygenase-2? And the answer is because it inhibited its cyclooxygenase-1. I know that aspirin inhibits both, but it's anti-platelet properties are due to cyclooxygenase-1 inhibition because cyclooxygenase-1 normally protects the stomach endothelium and normally is procoagulant via thromboxane A2. When aspirin destroys thromboxane A2, it's anti-platelet doses, baby. At low dose, aspirin is anti-platelet; that's why we call it baby aspirin. We used to call it baby aspirin because we used to give it to babies, but then we discovered something called Reye's syndrome. It happens to kids after taking aspirin, especially when they have an infection. Then we stopped giving baby aspirin to babies, and we gave baby aspirin to the elderly because it's baby, it's low dose, therefore it's anti-platelet, it's cardioprotective. In the UK, it's 75 milligrams, and in the United States, baby, it's 81 milligrams. At high doses or moderate to high doses, aspirin is analgesic, antipyretic, anti-inflammatory. In the UK, it's 300 milligrams, and in the United States, it's around 325 milligrams. Baby, you can get my perfectionist ultimate notebook + 20 lymphoma cases + 25 bleeding cases at patreon.com/medicosis.
Before you give aspirin, make sure that the patient is not allergic because aspirin is immunogenic and the patient has no increased risk of bleeding because aspirin will lead to bleeding because it's antiplatelet. Hello. How do we eliminate aspirin from our bodies? It's called zero-order elimination, baby, especially at high doses of aspirin. What the flip is zero-order elimination in pharmacology? There is a difference between first-order elimination and zero-order elimination. Today, I'll talk about the zero-order elimination: a constant amount is being eliminated per unit time. What the flip does that mean? Means the rate of elimination is independent of plasma concentration or drug amount in your body. Okay, what the flip does do both of these mean? It means that every four hours, for example, we get rid of ten milligrams. So we start with eighty milligrams of aspirin, then we have 70 after four hours, 60 after four more hours, 50… a constant amount, in this case, ten milligrams, is being eliminated per unit time. Here, it's four hours. The rate of elimination is independent of plasma concentration. When we had lots of aspirin in our plasma, we got rid of ten milligrams per four hours. When we have less aspirin in our plasma, we get rid of aspirin again, ten milligrams during four hours, the same rate of elimination. That's why we call it zero-order elimination. So the rate of elimination is independent of the plasma concentration of aspirin. There is no fixed half-life; the T1/2 is variable, and I can mathematically prove it to you, okay? So here is eighty milligrams. Half-life is the time you need for this amount to equal half, so eighty to become forty, four hours, and four hours, and four hours, and four hours. Four times four, according to my calculator, is sixteen. Then forty, in order for forty to become half, twenty, we needed only eight hours. The T1/2, the half-life, is variable; it was sixteen, then eight, then whatever; it's variable; it's not fixed because it's a zero-order elimination. And if you plot the amount and the time on the graph, it's gonna be a straight line, baby. Why? Because a constant amount is being eliminated per unit time. It cannot be easier than that, guys. Come on.
Thanks for watching. Please subscribe and join the tribe. Follow me on Facebook and Instagram. I have more than 90 cases on Facebook and go to patreon.com/medicosis to get all of my notes. I have 400 plus illustrated notes that I draw for my videos, and I have the fun about lymphoma as well as many cases. I Patreon, Patreon. Have come for/medical just… Thank you guys for watching. As always, be safe, stay happy, and study hard. This is Medicosis Perfection. A nose for medicine makes perfect sense. In the next video, we'll talk about the uses of aspirin as well as the side effects, so please subscribe.