Transcription
It's Medicos. Is perfection. Analysts are resuming our discussion about bleeding and coagulation disorders. It's a playlist, so please subscribe and see the pool. Save the playlist. Anyways, in the previous video, I have talked about acetylsalicylic acid, its clinical uses, or the indications. Today, we'll talk about the side effects, which is also known as adverse effects. However, what most students don't know is that side effects are not the same as toxicity. Side effects or adverse effects occur at the normal dose. Toxicity occurs at the overdose. Big difference. So, for example, you took like a pill of aspirin, and your doctor told you like take a pill every day, and you notice some side effects; these are side effects. Now, on the other hand, if you abandoned your three-year-old kid to jump on Facebook and your kid swallowed 37 tablets, this is called toxicity of acetylsalicylic acid, aka Salicylism. And with that being said, now let's get started. [Music] Repetition is the mother of pedagogy.
Acetylsalicylic acid, one of the nonsteroidals, it's antiplatelet, analgesic, diaphoretic, and anti-inflammatory. The mechanism of action irreversibly inhibits the cyclooxygenases via acetylation. It's called a reversible non-competitive antagonism. There is nothing that you can do to override it because when you have like compound A and compound B and they shared the same receptor, this is called competitive inhibition. When A inhibits this receptor, or I'm sorry, binds to this receptor and causes a certain action, if you want to inhibit A, add lots of B, and those lots of Bs will pick A outside of the receptor, and B will bind to the receptor. If it was a competitive antagonism, with aspirin, it's non-competitive antagonism. You cannot get anything from outside to pick the aspirin off the receptor. It's not going to happen, baby. It's also one of the reasons we have no antidotes to aspirin. Aspirin inhibits the cyclooxygenase; no thromboxane A2, no platelet aggregation. But unfortunately, all of the arachidonic acid is going to be converted into leukotrienes, which is bad for asthma patients. Does aspirin inhibit cyclooxygenase one or two? And the answer is both. Is aspirin antiplatelet because it inhibits one or two? And the answer is one. Is aspirin bad for your stomach because it inhibits one or two? And the answer is also one. At low dose, aspirin is antiplatelet; at high dose, aspirin is analgesic, antipyretic, anti-inflammatory. Beware of allergy and bleeding.
Now, the side effects of aspirin. If you have studied economics for five seconds, the scientific study of scarce resources which have alternative uses, you will realize that there are no solutions in life, only trade-offs. Aspirin has some desired effects: it's antiplatelet, analgesic, antipyretic, anti-inflammatory, but there has to be some trade-offs, such as bleeding, for instance. So, on one hand, aspirin protects you against thrombosis, but on the other hand, can also make you bleed. Welcome to life. But that's not fair. Shut up, and first define fair. Side effects of aspirin, acetylsalicylic acid. Now, the topic of today: first, bleeding. Please don't ever forget that if your professor asked you about side effects of aspirin and you'd like maybe asthma exacerbation, maybe renal, and you forgot to mention bleeding, okay, if I were your professor, I would come to your house and kick you in the butt, metaphorically speaking, because I care about you. Aspirin, honey, is antiplatelet, okay? So you forget your name, but you don't forget that aspirin can lead to bleeding. I mean, it's very easy. So what's the most common side effect of aspirin? Answer: bleeding. GI upset. Why? Because it inhibits the cyclooxygenase one. When there is no cyclooxygenase one, there is nothing to protect the mucosal endothelium or the mucosal lining of your stomach, so it gets hammered by acid, leading to peptic ulcer disease, also known as PUD, not to be confused with HUD, the Housing and Urban Development. Lost the metaphor completely. And as well as gastritis. Again, your stomach is being hammered by the acid because there is no COX-1 to inhibit it.
Hyperventilation. And this is weird. Why it's weird? Because most drugs inhibit the respiratory center in your brainstem, but now aspirin, baby, aspirin stimulates the respiratory center in your brainstem, leading to increased respiration. You breathe a lot. You breathe a lot when you do like this. You're washing out the CO2, and the CO2 is acid. The loss of acid is called alkalosis, at least where I grew up. This alkalosis is caused by your lungs, hence a respiratory alkalosis. And this is education as it should be: fun and engaging and robust. I just learned this word the other day: tinnitus, ringing in the ear. Very, very important, and unique to aspirin, okay? Sensory neural hearing loss, because again, tinnitus is the inner ear, and sensory neural is in like in the inner ear stuff, the external ear. So it's not conductive hearing loss; it's sensory neural. And on your exam, when you see tinnitus and the patient is on a drug, it's going to be aspirin most of the time. Respiratory alkalosis followed by metabolic acidosis. Why respiratory alkalosis? Because three seconds ago, I've told you that you were washing out the CO2 thanks to hyperventilation. When you wash off the CO2, this is rhetorical, okay? I got it. Thank you. How about metabolic acidosis? Have you heard like the aspirin is called what? It's called acetylsalicylic acid, so no wonder it's causing acidosis when it's metabolized, called metabolic acidosis. Also, aspirin will lead to lactic acidosis, and we'll talk about this later. So you have acetylsalicylic acid; this acid is causing metabolic acidosis. Aspirin will lead to lactic acidosis, which will cause metabolic acidosis, specifically the high anion gap metabolic acidosis, ultra-high anion gap, because the anion gap is high. What's the anion gap? It's the positive on one end, which is sodium, minus the negatives on the other end, which are the bicarbonate and the chloride. You subtract this from this, and you get the answer called the anion gap. When the anion gap is high and the patient's having acidosis, one plus two equals high anion gap metabolic acidosis. Aspirin can lead to a non-cardiogenic pulmonary edema. Translation: edema in the pleural cavity, which is not caused by the heart. It's not the heart's fault; your heart is fine and full of feelings and large because you suffer from hypertrophic cardiomyopathy. Please go see your doctor. Also, your feelings are not in your heart; they are in your brain.
Renal toxicity, big time. Why? Direct drug toxicity. This is called acute tubular necrosis. And if you remember pathology, we have two main types of acute tubular necrosis. We have the first one, which is hypoxic, when the kidney is not getting any oxygen. The other one is toxic, when the kidney is being beaten up by drugs, man, such as aspirin, called toxic acute tubular necrosis. Also, aspirin inhibits the cyclooxygenase. When there's no cyclooxygenase, there is no prostaglandin. Prostaglandin, back in the good old days, used to dilate the afferent arteriole, okay, of your glomerulus. When you dilate the afferent arteriole, you increase the GFR. This is normal prostaglandin, but now under aspirin influence, you have no prostaglandin; there is no increase in GFR because there is no dilation of the afferent arteriole. I hope this is clear. Aspirin is bad for your kidneys. Add another nonsteroidal with aspirin; take them at the same time for a long period of time; say goodbye to your kidney, yeah, and take their idiot called your doctor to the court next. Asthma exacerbation. Again, watch my video on the arachidonic acid pathway, because aspirin inhibits the cyclooxygenase; all of the arachidonic acid has been converted into leukotrienes, which are bad for asthma patients. What's AERD? It's called aspirin-exacerbated respiratory disease, yeah. Look, just pick up like any bunch of letters and arrange them together, and it's probably a disease in your body. God help us, and help all of the medical and nursing students all over the world. If you remember my words of wisdom that I have uttered before, there are only two ways to coagulate, but there are several ways to bleed. Aspirin, my friends, is one of those ways to bleed.
Next side effects: aspirin includes hyperthermia or fever. Why? Now pay attention, and let's go back to your biochemistry classes. At high dose, aspirin acts as an uncoupler in the electron transport chain in your mitochondria. What the flip is an uncoupler? An uncoupler is something that uncouples the electrons from the ATP. What the flip does that mean? It allows the electrons to flow; however, the energy is liberated as heat instead of ATP. What the flip does that mean, okay? Let's talk about normal first, then let's talk about aspirin and the uncoupling. Normal here is nice electron transport chain complexes, very nice stuff. You are transporting electrons and pumping protons. Oh, good, because the electrons are negative, protons are positive; they are kind of the opposite sides of the same coin. Get your head out of your sphincter. You're continuously shifting electrons and pumping protons, pumping protons, pumping protons, pumping protons. So protons are pumped here, and they are pumped here to the outside, to the outside of the intermembrane space. The protons are sick and tired of being sick and tired. Lots of protons outside; boom, they're going to rush inside. ADP plus Pi equals ATP. Welcome to the energy currency of yourself, called adenosine triphosphate. That's great; that's a great continuum between the electron flow and energy production. That's normal. Not with aspirin, baby. Aspirin is an uncoupler. The electrons are free to flow, nice and rosy, but you don't get to produce ATP anymore. Your energy is produced in the form of heat. And if you ask any engineer about it, they will tell you lots of heat called inefficiency, which means someone is going to get fired from the job. If we have two electric bulbs, here's the electric bulb A, and here's the electric bulb number B, letter B. A is hot, like it's 50% hot after one hour, whatever 50 percent means. B is just 1% hot after one hour. Which one is more efficient? And the answer is B, because it used most of the energy for light, and very, very, very little has been wasted in the form of heat. A is crazy; 50% or like lots of heat and fair, and the other is for light, which is very inefficient. Your electron transport chain under the influence of aspirin is very inefficient. You're flowing electrons; you're not producing ATP; you're just producing heat. In a sense, you have uncoupled the electrons from the ATP, which is a very deep and profound philosophical statement. So if you have a patient with like any rheumatological diseases and she is on high dose aspirin and she complains, every time I sit on a chair, I feel heat underneath, yes, this is called uncoupling. This is one possibility. The other possibility is that there was a morbidly obese person sitting on the chair before you, in which case don't blame the aspirin. If you are a visual learner and you like pictures and you have problems studying for pharmacology, microbiology, genetic diseases, or any stuff that requires heavy memorization, check out my friends at Picmonic. The link is in the description. It's just brilliant. For instance, warfarin is warfarin for everyone, but Picmonic, it's the war fairy, baby. It's great; it's visual. And then this is vitamin K, also known as Viking King. And as you know, warfarin will inhibit the vitamin K dependent factor. So this fairy will punch or shoot this Viking King with her bazooka. Once you see that with your eyes, you will remember it forever. Picmonic is not a sponsor of this video.
Side effects of aspirin continued: iron deficiency anemia. Now we're talking, especially in an elderly patient taking aspirin, post-naproxen, and NSAIDs together. I'll say goodbye to your cyclooxygenases, baby. No prostaglandins, no stomach protection because there is no cyclooxygenase one, no epithelial lining or mucosal secretion protection. Welcome to peptic ulcer disease land. GI bleed. When you bleed, you're losing blood. Blood contains red blood cells. Red blood cells contain hemoglobin. Hemoglobin contains heme and globin. Heme contains iron and protoporphyrin. Iron, I'm losing iron. Yes, this is called iron deficiency anemia. And in the United States, the most common cause of iron deficiency anemia is a GI bleed. In the developing world, like Egypt, the country that I came from, the most common cause of anemia is nutritional deficiency, okay? But what is the most common subtype or cause of anemia worldwide? And the answer, of course, is iron deficiency. Iron deficiency is the most common type of anemia. How to diagnose GI bleed? And this is a very important question for your board exam, especially for surgery. We are trying to figure out where the blood is coming from. Is it upper GI bleed or lower GI bleed? Because there is a big difference. For example, is the problem like you're bleeding from your stomach or bleeding from your colon? Big difference, because you want to treat it; you have to diagnose first, and then you treat. If the patient is vomiting blood right now, called hematemesis, then obviously the source of bleeding is the upper GI. Used to be idiot; the patient is vomiting vomiting blood right now, so of course the bleeding source is the upper GI. You cannot vomit blood from your colon. If your colon is bleeding, okay, why? Because it's in the stool. You cannot vomit blood coming from your colon unless you're upside down. So that's easy. If the patient is vomiting blood, upper GI, very easy, okay? However, what if the blood is seen in the stool? This is difficult because the blood could be coming from the lower GI, such as the rectum or the colon, or from the upper GI, esophagus or stomach, because the blood moves downwards to the stool even if the original source is the upper GI. This is called gravity, hello. So first, you look at the color of the blood. The color is black; probably from the upper GI. This is called acid, baby. Stomach has some acid; acid is capable of turning the blood very dark to the point of being black. Then if it's bright red, it's lower GI; it hasn't passed through an acid. And if you remember your physiology, only the stomach secretes acid in the entire GI tract. Whatever the blood was, it's not bright red, and it's not like it's kind of dark red; it could be coming from anywhere, and this is very confusing. You can do fecal occult blood test, red cells study, upper and lower endoscopy to know where the flip the blood is coming from. If you're studying surgery, this is a very important question: where is the GI bleed coming from? Is it at the upper GI or the lower GI? Challenging stuff. That's why all surgeons are walking around confused and without any hair left on their scalp, called baldness, which the doctors call male pattern baldness or alopecia, but politicians call it baldness.
Other side effects of aspirin: idiopathic thrombocytopenic. What does idiopathic mean? It means we are idiots and we don't know the pathology. We don't know why. It's probably immunogenic, but again, we are idiots, hence the name. Positive hemolytic anemia. It can make you bleed, baby. Drug-induced esophagitis, also known as pill esophagitis. Allergy, aspirin sensitivity syndrome, which is a pseudo-allergic reaction. So aspirin can cause allergy or pseudo-allergy. And aspirin overdose, on a very high dose, when your kid has swallowed 30 tablets or something around that, this is called salicylism or aspirin toxicity or salicylate toxicity. And this could be acute and chronic, and this will be the topic of the next video. Thank you for watching. I have the perfect nails ultimate notebook on my website called patreon.com/medicos. You get 20 lymphoma cases and 25 bleeding cases as a bonus from a generous guy like me. Also, if you want to know very sophisticated stuff about aspirin, I have a PDF on Patreon, and it's only $1. A PDF like lots of stuff. We get into details about aspirin and what's the number needed to treat aspirin and many, many great stuff. That's it for today. Please subscribe, hit the bell, and smash like. Follow me on Facebook. I have more than 90 cases there. You can get my notes and all of my illustrations at patreon.com/medicos. Thank you for watching. This is Medicos, perfect nails. Be safe, stay happy, and study hard.