Transcription
Hey guys, it's Medicals Perfect Nails. Continuing our bleeding and coagulation discussion. In the previous videos, we've talked about acetylsalicylic acid, like lots of things: clinical uses, side effects, zero-order elimination, salicylism, how does it sell, toxicity. I said today it's just a very, very quick review. If you have any problems understanding any stuff in this video, watch my previous videos. Plays with that being said, now let's get started. [Music]
Aspirin, the wonder drug, is also known as acetylsalicylic acid. No wonder it can cause acidosis. It's antiplatelet, analgesic, antipyretic, anti-inflammatory; one of the non-steroidals. It comes from the willow tree resin. Aspirin, aspirin, this a big A, aspirin is a trademark of the company that made it. Its mechanism of action is irreversibly inhibiting cyclooxygenase via acetylation. When you have no cyclooxygenase, you have no thromboxane A2, no platelet aggregation. It's called irreversible non-competitive inhibition or antagonism.
After taking the last aspirin pill, how long do you have to wait until the platelets restore their function? Called blood coagulation or primary hemostasis? 48 hours. Does aspirin inhibit cyclooxygenase-1 or cyclooxygenase-2? The answer is both. How about prostacyclin? We have two theories: Number one, aspirin doesn't inhibit prostaglandin I2. Number two, aspirin in the beginning inhibits it, but at the end of the day, it doesn't. Here is the arachidonic acid pathway: Aspirin inhibits the cyclooxygenase; no cyclooxygenase, no thromboxane A2, no vasoconstriction, no platelet aggregation. When there is no platelet aggregation, there is no blood coagulation. Called common sense, because A comes before B; when you inhibit A, you have inhibited B. But since you have inhibited the cyclooxygenase, now all of the arachidonic acid is being converted into leukotrienes. You have more leukotrienes than usual, and this is bad for asthma patients. That's why aspirin is bad for asthmatics, and there is even a disease named after this, called aspirin-exacerbated respiratory disease.
Three questions: Does aspirin inhibit COX-1 or COX-2? Both. Is aspirin antiplatelet because it inhibits COX-1 and COX-2? The answer is COX-1. Third question: Is aspirin bad for your stomach because it inhibits COX-1 and COX-2? The answer is COX-1. At low dose, aspirin is antiplatelet. At high dose, aspirin is analgesic, antipyretic, and anti-inflammatory. How do you eliminate aspirin out of your body? Juice cleanser? Now shut up. It's called zero-order elimination. A constant amount is being eliminated per unit time. The rate of elimination is independent of plasma concentration. Like every four hours, we are eliminating just ten milligrams. It doesn't matter in the beginning or at the end; every four hours, same ten milligrams. Therefore, the T half is variable. It took us 16 hours to get to the half of the amount, but next time it took us only eight hours. That's why T half is variable.
Indications of aspirin: prevents MI and MI recurrence; acute coronary syndrome—use TPA plus heparin plus aspirin. What's acute coronary syndrome? Unstable angina, non-STEMI, and STEMI—no ST elevation myocardial infarction; ST-elevation myocardial infarction. My handwriting is getting bad; I think I'm having a stroke. Prophylactic for atrial arrhythmia, Afib. Why? Because if, like, normally your heart should pump blood; in Afib, your heart is just tickling the blood, which is horrible. It can lead to blood stasis. According to this German scientist called Rudolf Virchow, we have the Virchow triad. Blood stasis can lead to blood coagulation. You can end up with a thrombus in your heart, which is bad. Can go everywhere, can go here, and can go long back and go to the brain, causing stroke—horrible. It's good also for TIA and stroke, ischemic stroke, prophylactic, weekly, therapeutic. We use aspirin for strokes mainly for prophylaxis. How do you know if it's ischemic stroke or hemorrhagic stroke? Non-contrast CT of the head. If it's hemorrhagic, never give aspirin, never give TPA, because the patient is bleeding, you stupid idiot. Aspirin is good for antiphospholipid antibody syndrome. We use two lows: low-dose aspirin, low-molecular-weight heparin. Aspirin is also good for multi-infarct or vascular dementia.
Clinical uses again: peripheral arterial disease, fever reduction, rheumatic fever, rheumatoid arthritis, osteoarthritis, and irritable bowel syndrome headache, Herxheimer reaction. Aspirin is protective against gallstone formation and colon cancer. Good for Kawasaki disease, why? It's protective against coronary artery thrombosis. Mondor disease, which is superficial thrombophlebitis of the vein in your chest wall, with niacin to reduce flushing. #flush the aspirin. Why use aspirin for Mondor disease? By the way, it ends in "-itis," when it ends in "-itis," it's an inflammation. Aspirin's anti-inflammatory. Welcome to common sense land. You can give aspirin for low-dose Afib. In fact, if the patient has Afib alone, give aspirin alone, forget about warfarin, ablation surgery, all of this crazy stuff. It's also good for temporal arteritis, but steroids, baby, don't forget the steroids, please.
Kawasaki disease: Why use aspirin? Risk versus benefit analysis. What's the risk? The risk is aspirin can lead to Reye syndrome. What's the benefit? Aspirin protects this kid against coronary artery thrombosis. So in most cases, it's safe to give aspirin to a Kawasaki disease patient: aspirin plus IVIG. There is only one or two exceptions when not to give aspirin to the Kawasaki disease kid, and the answer to this sophisticated question is available on patreon.com/4/medicalosis. Every drug on this freakin' planet has desirable effects and adverse effects, because according to economics, there are no solutions in life, only trade-offs.
Side effects of aspirin: If it inhibits platelets, it will lead to bleeding, duh. GI upset, peptic ulcer, reason gastritis, because it inhibits the cyclooxygenase-1. Hyperventilation, because it simulates the respiratory center. When you stimulate the respiratory center, increased respiratory rate, you're washing out CO2, you're washing out the CO2, leading to respiratory alkalosis. Tinnitus, sensorineural hearing loss, not conductive. Respiratory alkalosis followed by metabolic acidosis. Why respiratory alkalosis? Due to the hyperventilation. Why metabolic acidosis? Called acetylsalicylic acid, also because aspirin is an uncoupler of the electron transport chain. When you have no ATP from the mitochondria, you will shift to the anaerobic glycolysis, leading to lactic acid production, leading to metabolic acidosis. Which subtype of metabolic acidosis? The high anion gap metabolic acidosis. Hogman, non-cardiogenic pulmonary edema is a big deal. Don't ever forget that aspirin can lead to non-cardiogenic pulmonary edema. Renal toxicity: Why? First, aspirin is a drug, direct drug toxicity, called toxic acute tubular necrosis. Inhibits cyclooxygenase, no prostaglandins. When you have no prostaglandins, you have no increase in GFR; it's bad for your kidney. Asthma exacerbation, which we call it aspirin-exacerbated respiratory disease. I'm still in my mid-20s, but I'm spitting wisdom all over the place. There are only two ways to coagulate, but there are several ways to bleed, and my friends, aspirin is one of these several ways to bleed. The most common side effect of aspirin is bleeding. No, I think I need the red marker because blood is red, unless you are deoxygenated.
Side effects of aspirin: Hyperthermia. Why? Aspirin is an uncoupler. It uncouples the electrons from the ATP, allows the electrons to flow; however, the energy is liberated in, like, in form of heat instead of ATP. Which should be asked an engineer. That's very inefficient, or you can ask your crazy physics professor with thick glasses. When you have no ATP coming from the electron transport chain, you will shift to anaerobic glycolysis, which will lead to lactic acid, which will lead to Hagman. Aspirin can lead to iron deficiency anemia because aspirin is bad for your stomach: no prostaglandin, no stomach protection, peptic ulcer disease, GI bleed. When you bleed, you're losing red blood cells. When you're losing red blood cells, you're losing hemoglobin. Hemoglobin consists of heme and globin. Heme is made of iron and protoporphyrin, and you will lose… when you lose iron in the vomitus or in the stool, you end up with iron deficiency anemia, which starts as normocytic but turns into microcytic anemia. What's the most common type of anemia worldwide? The answer is iron deficiency anemia. What's the most common cause of iron deficiency anemia? It depends on where you live. If it's in the developed country like the United States, really Canada, whatever, Japan, it's probably age-relatedly. If it's in a developing country like the country that I came from, called Egypt, the most common cause of iron deficiency anemia is nutritional. Aspirin, unfortunately, can lead to idiopathic thrombocytopenic purpura, positive hemolytic anemia, drug-induced esophagitis, allergy, aspirin sensitivity, and aspirin toxicity, called salicylism.
There are some medications that you should never combine with aspirin, and they include warfarin, SSRIs, alcohol, penicillin G, and vitamin C. Salicylate poisoning, acute or chronic. When is aspirin toxic? Depending on your body weight, more than 15 milligrams per kilogram. What are the signs and symptoms of salicylism? Tinnitus, nausea, vomiting, abdominal pain, tremors, fatigue, stupor, and literally because your body is trying to stay still to decrease the acidosis or not to make it worse, shortness of breath, hyperventilation, fever, respiratory alkalosis followed by metabolic acidosis, pulmonary edema. There are three phases of salicylate poisoning, and I've talked about this in a previous video. The most common cause of death in case of salicylate poisoning is cardiopulmonary arrest due to pulmonary edema. Diagnosis of salicylism: You need a CBC, CMP, arterial blood gases to measure the pH and CO2, acidosis versus alkalosis, and all the stuff. Blood cell, level of blood glucose level, and urinalysis. Blood glucose is low when you give fluid, that please choose the D5W because it contains dextrose, which is kind of the same as the glucose. If you love medical mnemonics, please try Picmonic, and the link is in the description. These guys are amazing.
Treatment of salicylism: There are no antidotes for aspirin; don't believe your salesmen. ABC is first: airway, breathing, circulation. Gastric decontamination by activated charcoal, IV fluid to maintain the effective blood volume and thereby the urine output, which is the fifth vital sign, which is profound. Aspirin overdose can lead to dehydration. When you give IV fluid, if the glucose level is low, choose the D5W; if the glucose is normal, choose the normal saline, which is 0.9 percent sodium chloride solution. Alkalization of urine for sodium bicarbonate, hemodialysis when everything fails. Aspirin is an acid; if you want to get rid of an acid, put it in an alkaline medium, called alkalization of the urine. If you want to know more about aspirin, check my previous videos and check this PDF on patreon.com/4/medicalosis. Thank you so much, guys, for watching. Please subscribe and hit the bell. Follow me on Facebook for cases and get my notes and many other cases on patreon.com/4/medicalosis. As always, be safe, stay happy, and study hard.