DIP Episode 606 - Drug Interactions For The USMLEs (Step 1-3)

Alright, welcome to episode 606 of the Divine Intervention Podcasts. Into this podcast we're going to be examining a topic that is extremely, extremely, extremely high yield for the USML Es. You will see this material on your exams. You don't study it, you're doing it at basically at your own risk. I'll try to see if I can compress everything into one podcast, but if I cannot, it'll be a part two. This podcast is going to focus on drug interactions, high yield drug interactions. High yield drug interactions. They love to test the stuff on step one, step two CK, step three, level one, level two, level three. You will see this material on your exams. You need to know this. There's no ifs, no aunts, no bots about it. Alright, so let's begin. So what if they give you a question about a person that has Vavila Efeb. And then the person was given an antibiotic. And as this person was taking this antibiotic, you notice that they started bleeding from their nose, they started having gum bleeding, you know, and you check their eye now and their eye now is going to significantly. Well, what's going on here? Well, this is clearly Warframe toxicity, right? The thing is, Warframe has so many interactions, its ridiculous, how many interactions they have. You can make almost like 10 different Warframe drug interaction questions on your exams, right? So you may wonder, but divine in the vignette you just said, the person was not on Warframe. How did you get to Warframe?

Well, the person happens to have what is known as Vavila Efeb. They have a feb that involves a valve problem. Remember, whenever a person has anybody that has a feb has to be an anti-coagulation, that's a rule you should basically searing your mind for the USME Ls. If you have a feb, you need to be an anti-coagulation. Now if you have a feb that's from a Vavila reason, right? Like my trusted nurses or whatever, you have like a prosthetic valve and you have a feb, you need to be on Warframe. Warframe is pretty much your only option on the USME Ls exams, right? So the thing is, there are many, many drugs that can interact with Warframe, right? So they can be, they will classically make it a person that is chronically on Warframe for whatever situation. And then you place them on some kind of drug, usually it's going to be an antibiotic and it's going to raise their Warframe levels, right? So one key thing to know for the USME Ls is for Warframe, what are these drugs that interact with it and what are the mechanisms, right? Like for example, one classic antibiotic can be seen on your exams. Probably the most common one is going to be a macrolead, right? Macroleads, the inhibitor ends on known as CYP3 A4. CYP3 A4 is an enzyme that helps us break down a metabolized Warframe. So if you take a macrolead and you take Warframe and you're already on Warframe, you will inhibit the metabolism and breakdown of Warframe.

So you're going to have high Warframe levels, that's going to cause you to get in trouble, right? Another antibiotic you may see on your exam that can cause Warframe toxicity is a fluoroquine alone, right? Fluoroquine alone is the inhibitor side of the chrompy for 15 enzyme known as CYP1 A2. CYP1 A2. When you shut down CYP1 A2, that's also going to reduce the metabolism of Warframe. CYP1 A2 is one of those enzymes that help us break down Warframe, right? That can actually raise your Warframe levels and that can cause problems, right? And actually one other thing that fluoroquine alone do, that's going to hide you to know with Warframe metabolism, is that fluoroquine alone is the displaced Warframe from argument. Because argument is a big protein we find in the bloodstream. It's like a carrier protein for many things. One thing it carries is fluoroquine alone, right? So if you displaced Warframe from, because remember many times when, when something is bound to argument, it doesn't necessarily do what it's supposed to do in the body. It's almost like you put it in this neutral pool. But when you displace it from argument, it becomes more, it becomes active and then you begin to have a drug effect. So that's another mechanism behind fluoroquine alone causing a causing problems. Another antibiotic you may see with Warframe is trimethoprymsofamethoxazone, backtrim, right? Backtrim inhibits an enzyme known as CYP2 C9. That literally breaks down Warframe, right?

So again, if you take backtrim, trimethoprymsofamethoxazone, and you're already on Warframe, you can get in trouble and raise Warframe levels, right? And also, backtrim displaces Warframe from argument, right? Backtrim displaces Warframe from argument. Many resources for whatever reason do not talk about this, but this is actually something that is actually pretty high yield to know, for example, right? And this CYP2 C9 enzyme that I discussed with Warframe, that enzyme also is inhibited by metronidousol. So again, if you're taking metronidousol and you're taking on Warframe, again, you can really raise your Warframe levels, right? So do you see why these days will prefer more of these novel oral anticoagulants because they have fewer of these problems compared with Warframe? But again, certain situations where Warframe is pretty much your only bet, especially if you have a very high yield indication to know for your exams, right? Or do you just give it to a person? Because they want to test the drug interaction. And Warframe is also pretty cheap, right? Warframe is also pretty cheap, even if he has all these problems, right? So you already know the cost of healthcare in this country and insurance and all those fun things. All right. Now, one other thing I just want to say in general, in general, in general, with Warframe, is that in general, when you take antibiotics with Warframe, you're kind of going down on a slippery slope. Let me explain why. How does Warframe work?

We know that Warframe works by inhibiting vitamin K-boxyreductase. When you inhibite vitamin K-boxyreductase, you're going to decrease the gamma-capoxylation and activation of your clotting factors, factors 279 and 10, and I guess some proteins like proteins CNS. Now, what do you think vitamin K-boxyreductase uses as a co-factor? Hmm. I wonder why. I wonder what it will be. It's going to be vitamin K, right? And vitamin K is made in the body by a gut flora. So if you take antibiotics, you will kill off a lot of your gut flora. When you kill off a lot of your gut flora, you're killing off a lot of your vitamin K production in the body. If you kill a vitamin K production, that's a problem. Because if you're Warframe, you know Warframe is inhibiting vitamin K-boxyreductase, but maybe there is at least a little bit of vitamin K-boxyreductase working, right? Even in the presence of Warframe, right? But if you kill off the source of vitamin K, aka your gut flora, then you won't have at least some vitamin K to activate the vitamin K-boxyreductase, that at least may still be working in the presence of Warframe, right? So you're pretty much potentiating the Warframe toxicity because you're potentiating decreased activity of vitamin K-boxyreductase. Again all these things are very high yield to know for your exams. And many resources don't emphasize this, but it's extremely high yield to know for your test, right?

And then another thing I'm going to say, I promise I'm going to stop talking about Warframe in a moment here, but another thing you want to know about Warframe, right? They can give you a question about a person that's on Warframe and then, you know, they've been having headaches or they've been having chronic joint pain and they've been taking a set of menophanes for their joint pain and then they start having all these bleeding complications. Well, think of a set of menophanes, right? Think of a set of menophanes. A menophanes can also interact with Warframe, right? Many of you know that a set of menophanes is something that can destroy the liver, right? And you know the metabolite that destroys the liver. You know that it's called any PQI. Any PQI is very liver destructive. That's the thing that primarily messes up the liver in a set of menophanes toxicity, right? Now, the thing is, and many times you know you're like, oh, let's use an acetylocysteine to kind of help us with that. But any PQI also has another destructive purpose. Any PQI has the ability to inhibit vitamin K epoxide reductase, right? Any PQI literally can inhibit vitamin K epoxide reductase. When you shut down vitamin K epoxide reductase, you're going to potentially, you're going to potentially basically, Warframe toxicity, right? Because again, we know that Warframe, the way it works, is by inhibiting vitamin K epoxide reductase. Okay, what if your body remakes some new vitamin K epoxide reductase?

And it's at least, at least that's kind of balancing out Warframe's anti-cogular defect. But if you bring something else on top that shuts that down, that can get you in a lot of trouble, right? Now, another classic drug interaction on our friends at the MBMS love to test is they can give you a question about a person that is on chronic pharmacotherapy for osteoarthritis. And then the person is also diagnosed with hypertension and they start an anti-hypertensive. And then their creatinine rises a lot, right? When you see that kind of presentation, what should you be thinking about? Well, I would hope you're really thinking about the interaction between an NSAID and an ACE inhibitor or an ARB, right? So remember NSAI Ds are like even aspirin because think about it. What are the people that may be taking aspirin and an ACE inhibitor together? Huh, gee, it's going to be people that have like heart failure, right? Let's say they have the heart failure from an ischemic cardiomyopathy, right? Well, if you think about it, people that have had like ischemic cardiomyopathy like an MI, they have to be on aspirin, right? They have to be on aspirin. Many times they're going to be on that aspirin indefinitely, right? Or at least they can be on it for the first 12 months after they have had a stain pleased in their hearts, right? But again, many times they're going to be on it indefinitely. Well, aspirin or an NSAID, right? Again, I'm bringing in NSAI Ds here.

You know, typically for a person who has had a heart attack, you're going to put them on aspirin, not an NSAID, right? But they kind of do the same thing, right? They inhibit a cyclooxygenase. When you inhibit cyclooxygenase, you're going to decrease the production of prostaglandins. When you decrease the production of prostaglandins, that's going to cause a constriction of the afrin material because prostaglandins dilute the afrin material. But if you shut down prostaglandins synthesis, you're going to lead to constriction of the afrin material. When you constrict the afrin material, that's going to reduce the profusion of the glomerular capillaries. That's going to reduce the hydrostatic pressure within your glomerular capillaries. If you reduce the hydrostatic pressure, that's going to lower the GFR because you're going to have less filtration and that's going to raise your creatinine, right? But if you then add another risk factor on top that can lower your GFR, like an ACE inhibitor and ARB that can get you in trouble. Well, how does that happen? Remember ACE inhibitors and AR Bs, right? They basically downregulate the activity of angiotensin II. Angiotensin II is a very potent efferent atti-r-a-triola constrictor, efferent atti-rola constrictor. So if you give an ACE inhibitor and ARB and you downregulate angiotensin II activity, you're going to dilute your efferent arterial, right? It's not going to be constricted anymore.

And if you dilute your efferent arterial, that is going to draw blood away from your glomerular capillaries. If that happens, if that happens, if that happens, if that happens, you're going to have less hydrostatic pressure within your glomerular capillaries. That is going to cause your creatinine to rise, right? Because again, your GFR is being reduced. If you reduce hydrostatic pressure within your glomerular capillaries, you're going to reduce your GFR because you're reducing filtration. That's going to raise your creatinine. Right? In fact, this is, this thing I just explained is why ACE inhibitors or AR Bs, they can normally raise your creatinine by a little bit when you start them, but it shouldn't be raised by more than 30%. Right? But when you have another risk factor on top, like an NSAID, right? Or an aspirin, right? Two things, conveniently, that can decrease GFR, that can get you in a lot of things. You're going to have trouble, right? And you notice I try to emphasize the mechanisms behind the GFR decreases. They're kind of different. They're kind of different depending on what you're dealing with, right? ACE inhibitors, AR Bs, they dilute the efferent arterial, aspirin, and NSAI Ds, they constrict the afferent arterial. All right. Now, remember, what if they give you a question about a patient, they tell you that she's a 27-year-old female and that she missed her period, right?

And you're told that all she was recently started on some kind of, you know, that she's a healthy female, she has been on OC Ps, but she was recently started on some kind of, you know, she traveled to a foreign country and then a TB skin test when she returned was positive, right? And then now she has, you know, basically missed that period in detail that a urine pregnancy test is positive. You know, she was also started on like maybe like a latent TB therapy or whatever. Why did this person get pregnant? Well, think of OC Ps and interactions, right? Think of OC Ps and interactions with SADO-GREMPI-450 Inducers, right? With SADO-GREMPI-450 Inducers. This is very, very high yield. This is very, very, very, very high yield to know for your exams, right? In general, taking an OCP and a SADO-GREMPI-450 Inducer is not a good idea. And the one the most frequently love to test this with is with RIFAMPIN, right? RIFAMPIN or RIFAMI-CIN, right? Basically, RIFAMPIN, RIFAMI-CIN, the Indus SADO-GREMPI-450 enzymes, especially like CYP3 A4. CYP3 A4 is a very critical enzyme that helps us break down OC Ps, right? Helps us break down OC Ps. So the thing is, if you take a CYP3 A4 Inducer while you're taking an OCP, then you'll increase the amount of CYP3 A4 in the body. You have more accelerated metabolism of that OCP. As you have more accelerated metabolism of that OCP, guess what's going to happen? Your OCP levels are going to fall. You're pretty much decreasing the half-life of that OCP.

That's going to cause you to get pregnant. They can literally give you this exact same kind of vignette in a person that has vitamin D deficiency. And you're giving them vitamin D supplementation. But that vitamin D supplementation they're getting doesn't seem to be working. It doesn't seem to be helping. The vitamin D levels in the body are not rising. Now, again, if you induce CYP3 A4 50 enzymes with a CYP3 A4 50 inducer, that can cause you to get in a lot of trouble, especially re-famping. That can cause you to get in a lot of trouble because you have accelerated metabolism of vitamin D, right? So you'll basically be getting little if any effect from that vitamin D, right? Now, what if they give you a question about a person? They tell you that this person has a history of gourd and the person has been on, you know, pharmacotherapy. This person was recently diagnosed with Hashimoto's thyroiditis. And you're told that the person was pleased on pharmacotherapy for Hashimoto's. But that the person, you know, they at a full of visits like three months later, they still continue to complain of symptoms. And you're told that their TSH, right? Their TSH is still markedly elevated, right? What's the mechanism behind the side effect that they have or behind their field response to liver thyroxin? Well, it's because of reduced bioavailability. Pick the answer that talks about reduced bioavailability. So what's the mechanism there?

Well, if you really think about this, this person has gourd. This person has gourd. Well, if you have gourd, chances are you're taking some kind of antithead, right? The problem with antitheads is that antitheads love to kill eat stuff. They love to kill eat stuff in the GI tract. They love to kill eat things like liver thyroxin. They love to kill eat things like tetracycline, right? They love to kill eat things like fluoroquenolose. So you will not get any effect from those drugs if you're taking them and you're taking an antithead at the same time, right? So that's why this person is not responding to liver thyroxin therapy because that liver thyroxin is being killated. So you're reducing the bioavailability because it is not being reabsorbed into the blood strain. It is not being reabsorbed into the blood strain, right? So please, they can literally write the same vignette in a person that's taking an attetracycline for like Lyme disease and they're not getting better or they're taking an attetracycline for some other purpose, they're not getting better. Repressing that's taking a fluoroquenolose for some purpose and they're not getting better. Again, liver thyroxin, fluoroquenolose antithracycline, they are killated by these antithids, right? Please, this is very, very high up to know for your exams. And I guess I can throw in a plug here for antithids, you know, especially these divalent ions, you know, like calcium, for example.

Remember, calcium will find you a lot in bones. That actually explains the mechanism behind how tetracycline can cause a lot of bone problems, right? Because a lot of calcium in bones. And the clint really, really love to bind to calcium, right? Okay, now what if they give you a question about a patient, they tell you that this patient has a history of a, you know, atherosclerotic cardiovascular disease and the person is on, the person is on pharmacotherapy for angina, right? But that the person has been having marital problems with his, you know, with his wife and he was placed on a pharmacotherapy for erectile dysfunction. And then now this person, whenever they rise out of bed in the morning, you know, that he had like one or two falls. And then they can see which of the following is the most likely mechanism behind the patient's increased propensity to fall in, right? Or, you know, or something along those lines. Well, if you think about that, you want to think about the combination of a cell, then I feel an unmitrate, cell, then I feel ununitrate, right? So the person is probably unitrates for their angina. And then that nitrate causes a lot of, you know, remember, nitrates are vinyl dilators. They're very potent vinyl dilators. So they can crush your preload. They can literally do what? They can literally crush your preload. When you crush a person's preload, when you crush a person's preload, right? You're reducing the amount of blood going back to the heart.

That's going to reduce the acrostic output. If you reduce the acrostic output, that can cause hypotension, right? Now, we know that cell, then a fail, is a phosphodiesterase 5 inhibitor. When you inhibit phosphodiesterase 5, you're going to increase cyclic GMP activity, right? When you increase cyclic GMP activity, cyclic GMP leads to a lot of visual dilation. So when you're combining those two things that can really, that are very visual active agents, right? That can cause your blood pressure to drop significantly, can cause your blood pressure to drop precipitously. And that can through into orthostatic hypotension, right? You know, so they can test orthostasis with that. Or they can test the presence that, whenever they rise out of bed, they just kind of fall to the ground, right? Because they have decreased profusion of the brain. Again, that interaction is very, very high, you know, for your exams, right? Now, what if they give you a question about a patient that is placed on, they give you a question about a patient that is on pharmacotherapy for major depressive disorder or generalize anxiety disorder? And then you're told that this person was, you know, recently started taking some kind of herbal supplement, right? And then the person presents to the emergency room because he's been having like shaking of his hands, you're told that he has like increased deep tendon reflexes and all those things and has myoclonus.

When you see something like that, I would really, really hope you're thinking about serotonin syndrome, right? I really hope you're thinking about serotonin syndrome, right? They love, love, love, love, love to test serotonin syndrome on the exams because there are so many interactions, many, many drug interactions that they can test with serotonin syndrome, right? Like for example, they can test about a person that, you know, sticking an SSRI and also taking St. John's words, right? Taking an SSRI, but also taking St. John's words. St. John's word is a herbal supplement, right? But it also has pro-serotonergic properties. It has pro-serotonergic properties. It can cause problems in people, right? That can absolutely cause serotonin syndrome. Or they can give you a question about a person that is taking an SNSRI and, you know, the person is on Parkinson's disease therapy, right? Like a monomyneoxidase inhibitor, like cellulogen, for example, right? When you inhibit monomyneoxidase, you're going to dig, monomyneoxidase helps us break down serotonin, right? So if you're on an SSRI and then you take a monomyneoxidase inhibitor, like cellulogen, for example, now we use for Parkinson's or any M-O-I that we use for, you know, depression, like, Isocarboxyze it, for example. That can raise your serotonin levels because remember, by inhibiting M-O-I, by inhibiting monomyneoxidase, you will stop breaking down serotonin.

So you're raising serotonin levels in the presence of you taking another drug, like an SSRI that can cause serotonin syndrome, right? Even they can give you a person that is already on an SSRI chronically for some mood disorder. But in addition to that, the person then starts an antibiotic, right? What antibiotic is going to raise your SSRI levels, right? I mean, what antibiotic is going to cause serotonin syndrome? Well, think of lignisolid, right? You can give your person that has like a MRSA infection. Lignisolid, lignisolid, lignisolid, lignisolid, lignisolid, lignisolid. What does lignisolid do? Lignisolid is a monomyneoxidase inhibitor. Remember, it's a 50s inhibitor, right? That can cover MRSA very well and vancomycin resistant interococcus. But it also inhibits, it also inhibits monomyneoxidase. So it can decrease the metabolism of serotonin and that can get you in a lot of trouble. All right. Now, what are some other SSRI interactions to know, right? Again, with serotonin syndrome, well, think about SSR Is and Tramadol. SSR Is and Tramadol, Tramadol, Tramadol, Tramadol, Tramadol has serotonergic activity, right? Again, if you combine it with an SSRI, you can get it in a lot of hot water, right? Another interaction to also keep in mind is like an SSRI and triptans, right? Like suma triptans. Remember, suma triptans is used for migraines. How do triptans work? Well, triptans are serotonin receptor agonists.

If you combine them with an SSRI, that can absolutely positively raise your risk of serotonin syndrome, right? Again, please, all these things, this is a very detailed podcast, but it's a very, very high your podcast to know and it's not enough to just know the interaction. You need to know the mechanism behind the problems that you face, the mechanism behind the problems that you face. All right. Now, what if they give you a question about a patient that, you know, has been on starting therapy for the longest time? And then the person is placed on another lipid-lorean medication in addition to the starting. And then you're told that the person has been completely of a lot of myelges and he creatine canis is elevated. Well, think of statins and fibres. Think of statins and fibres. Think of statins and fibres, right? The thing is, it is very high you to know this, that if you're already on a starting, take enough fibre in addition to that is not a good idea. You know why? Because fibres, they can shut down the breakdown. Basically, statins and fibres, they can shut down the breakdown of each other. So that can raise the levels of each, right? Especially fibres. Especially gem fibres, or gem fibres is a very, very big corporate here. It can raise your starting levels, right? If you raise the starting levels, you can increase the presence risk of ruptal. My honest, just remember, statins can cause my uplifting. Statins can cause my uplifting, right?

And then there is this enzyme that breaks down statins. It's known as OATP1 B1. OATP1 B1. OATP1 B1 is inhibited by macrolids, especially clarithromycin, right? If, so if you're taking a starting and you're taking clarithromycin, for example, a macrolid, that can shut down the breakdown of those statins. You can raise your starting levels and you can get in a lot of trouble. You can get in a lot of trouble. Now, let's talk about the world of anti-epileptic drugs, right? Anti-epileptic drugs. Anti-epileptic drugs, especially carbamazepine, phenetoin and phenobarbidol. Caramazepine, phenetoin and phenobarbidol. I kid you not. They love to test these anti-epileptic drugs and how they can interact with many other things on the USMELIS. See, there are many, there's like lots and lots of drug interactions we can talk about today. But again, I'm literally just focused on the ones that characteristically show up on the USMELIS exams, right? So what are some classic ones to know? Basically, if you're taking an anti-epileptic drug, if you're taking an anti-epileptic drug, and something that inhibits cytochromp 450, that can raise those anti-epileptic drug levels. The anti-epileptic drug levels, right? It can raise those levels, right? So the thing is, there are many cytochromp 450 inhibitors, but what are the classic ones they love to test on the exams? They love to test cymedidine. They love to test macrolips, especially erythromycin and chlorythromycin, erythromycin and chlorythromycin.

And they also love to test flukonazop, okay? So don't get me wrong, there are many cytochromp 450 inhibitors to know for your tests, but these are the classic ones they love to test in the context of drug interactions. Cymedidine, erythromycin, chlorythromycin, flukonazop, right? These things are very potent cytochromp 450 inhibitors. When you hear B-cytochromp 450, you're gonna shut down the metabolism, right? The breakdown of anti-epileptic drugs, especially which ones, carbon mesopene, then ito-infinobarbitol. You can potentiate the effects of those drugs, you can have a lot of toxicity with those drugs. Now on the flip side on the other edge of things, how about anti-epileptic drugs and lowering their levels, right? They'll classically give you questions in people that are taking one of these anti-epileptics. And then you notice that they start having more frequent seizures. Like they'll tell you that, oh wow, the seizures have been well-controlled for the longest time. And then out of the blue, they start having seizures. And then they tell you that, oh, this person recently started taking some kind of medication. Well, the thing is, if you take an anti-epileptic drug and a cyclone P450 inducer, a cyclone P450 inducer, a cyclone P450 inducer, right? That's going to accelerate the metabolism, accelerate the breakdown of these anti-epileptics. You're gonna lower these anti-epileptic drug levels and that's gonna cause problems.

Again, what are the classic anti-epileptics they love to test with these? They love to test this with what? With what? With what? They love to test these with, with carbon mesopene, thinitone and phenobarbitol. Phenobarbitol is probably less frequently tested, but carbon mesopenin phenobarbitol in, oh my goodness. They love, love, love, love, love to test those things. So please, make sure, please, make sure you know those drug interactions, right? In fact, one thing I forgot to say when I was talking about SSRI, is that SSRI is, again, all the serotonergic things, right? Like combining an SSRI and an SNRI, or combining an SSRI and an MEOI, or combining an SSRI and a tricyclic and anti-depressant, that can absolutely get you in trouble with serotonin syndrome, right? And honestly, I think I also forgot to say something with statins. There's so many of these things they can test on the exams. Please, like I'm serious. It may look like I'm joking in this podcast, but I'm trying to make this a more lighthearted podcast. This stuff is very, very high up to know for you exams, right? And I know it's sadly a lot of memorization, but there's also a lot of understanding required. Again, no interaction, no the mechanism, and you're gonna be good in for your test, right? Statins and the thing is, they love to test these particular drugs, because these drugs are commonly used in medicine, right? They're very widely used. How many people are not on statins in this country, right?

Even worldwide, right? So statins also can actually cause a... If you're taking a statin and a warframe, and warframe, that can actually cause problems, right? Statins and warframe actually interact. Statins and warframe actually interact. Well, how do they interact? Well, the thing is, see, CYP2 C9 and CYP3 A4, they both break down... They both break down statins and warframe. So it's like, oh, statins, CYP2 C9, CYP3 A4, they're break down statins, right? But also CYP2 C9, CYP3 A4, so breaks down warframe. So you have competition. You have these two drugs that are broken down by the same kind of enzymes, but the same kind of cyclone P450 enzymes. So if you're taking these two drugs at the same time, which is not uncommon, there are many people that are on warframe and on a statin, but we're trying to prevent that these days in healthcare, right? They're competing for breakdown, right? So obviously one is gonna be broken down more than the other. And the one that is not broken down as much, you're gonna raise levels of that thing, especially warframe, especially warframe, and that can cause your INR to rise up, right? That can cause your INR to rise up, right? That can cause your INR to rise up, right? And again, I talked about the interaction between cell-denafil and nitrates, but I think another interaction that's useful to this cause is between cell-denafil and cyclone P450 inhibitors. So they're gonna P450 inhibitors.

So they're gonna P450 inhibitors, especially symedidine, right? Especially symedidine, especially symedidine, and erythromycin, and also like your connozoles, like itchroconazol, itchroconazol, those things can shut down the breakdown of cell-denafil. They can shut down the breakdown of cell-denafil, and that can raise your cell-denafil levels, right? Because again, they know that, ooh, everybody knows cell-denafil plus nitrates on safe, dropping blood pressure, don't do that. But if you're taking cell-denafil, and you're taking a cyclone P450 inhibitor, especially which ones, especially which ones, right? Symedidine, itchroconazol, chiroconazol, those can raise your cell-denafil levels, and that can cause cell-denafil toxicity, right? Cell-denafil toxicity. All right, now, one of the interactions I wanna talk about, right, you can give you a question about a person, and this person is on, let's see, how do I put this? This person is on a multistabilizer, right? And then they were recently diagnosed with hypertension, and they were pleased on an anti-hypertensive. And then you notice that, ooh, this person has now been having tremors, you know, they've been having altered mental status, and all these things. Well, what drug interaction do you wanna think about? Do you wanna think about a person that's taking a diuretic and taking lithium, right? You can cause lithium toxicity when you're taking a diuretic. So what's the mechanism behind a diuretic causing lithium toxicity?

It's actually kind of straightforward, but actually this is very high you to know for your exams. See, if you, how does the body work? See, the body, one place that the body reabsorbs sodium and lithium in, is in the proximal tubule. This is something many resources don't cover. This is something many people do not know. But sodium and lithium, they are absorbed in many parts of the kidney, but for purposes of our discussion, I want you to know that lithium and sodium are reabsorbed in the proximal tubule. And the thing is, if you think about it, there's not many diuretics that work in the proximal tubule, right? Most diuretics work in more distal parts of the nephra, right? So like for example, what's like probably one of the more common diuretic classes that are taken for people that have high blood pressure? It's gonna be a thazide diuretic. Thazide diuretics, they work at the level of the distal-convoluted tubule to inhibit the sodium chloride's importer, the sodium chloride's importer. Well, the thing is, if you start on a diuretic, those diuretics are gonna cause you to become volume depleted, right? Because they are blocking reabsorption of ions in your kidneys. That's gonna take water along with these. This is gonna cause you to be volume depleted. Your body is not going to be happy with that. Your body's gonna be like, man, why am I losing all these ions in the more distal parts of my nephra, like the distal tubule? So your body's gonna be like, huh, you know what?

I will compensate. How am I gonna compensate? I'm gonna compensate by literally reabsorbing more sodium, more sodium in the proximal tubule. Reabsorbing more sodium in the proximal tubule. When you reabsorb more sodium in the proximal tubule, right? Then, even if you have these drugs that are inhibiting your distal nephron, it's not gonna be a big deal anymore to you. You're gonna be like, whatever, whatever, I'm good. Why can't you say that? Because now, now, now, you've got into a point where some of those ions that could have been wasted at the distal nephron, they have been reabsorbed at the proximal tubule, right? That's why after a while, you know, like your body adjusts. Your body is a very smart system. God created a very good body, right? Your body adjusts to those diuretics. They still work. They still work. Don't get me wrong. They still work. They're still effective. But again, your body begins to compensate by reabsorbing more of that sodium in the proximal tubule. Well, the thing is, sodium and lithium are pretty similar. If you remember back to general chemistry from college, sodium and lithium, they are both in group one of the periodic table. So many things or many transporters that can help with sodium reabsorption can absolutely help with lithium reabsorption. In fact, let me tell you this. Let me tell you something. Lithium is smaller than sodium.

So because lithium is smaller than sodium, if sodium can go through a transporter really well, do you really think that lithium can now go through that transporter as well? It absolutely can. It absolutely can. It absolutely can. It absolutely can. So when your body is compensating for that diuretic, when your body is compensating for that diuretic, by increasing sodium reabsorption in the proximal tubule, well, guess what's also having increased reabsorption? Lithium. And as you increase the reabsorption of lithium, you're going to increase your risk of lithium toxicity. You're going to increase your risk of what? Of lithium toxicity. That is very, very, very, very high yield to know for your exams. Because as more lithium is reabsorbed, you're going to have more toxicity. Now, the thing is you can actually broaden. You can actually broaden your application of this principle. Basically, states of volume depletion can raise your risk of lithium toxicity. Because again, when you have a state of volume depletion, you're going to have increased sodium and lithium reabsorption at the proximal tubule. Because your body is trying to hold as much sodium as possible. So they can hold as much fluid as possible to counteract that volume depletion that you have. So if a person is like dry for whatever reason, less than half high-povalymiq shock, and the only lithium has a most stabilizer, they can have lithium toxicity. So make sure you can make these integrations.

Make sure you can put all these stains together. Make sure you can put all these stains together. Please, these things are very, very important to know for your exams. Please, this podcast is probably like, I can probably put in like a top 20 podcasts that I've made. I've made a lot of higher podcasts in my life. But this one is pretty high yield. You're going to see the stuff on your exams. And this is one of those things where there's no test-taking strategy that will prepare you for it. You either know it or you don't know it. This is, I would almost equate the importance of this podcast to almost as important as my risk factors podcast, which as you know are like super, super, super high yield. All right. So I think maybe one of the, let me talk about one of the drug interactions. So many of you know that at the principal cell of the collecting duct, right? Sodium gets reabsorbed through that in a channel. And that triggers the excretion of potassium. If you shut down that system, if you shut down that system, if you shut down that system, that can cause problems, right? So like, backtrump, for example, try and prevent yourself from the docks as well, shut down that in a channel. If you shut down that in a channel, you're going to stop excretion potassium. You're literally going to stop excretion potassium into the urine. That's going to raise your serum potassium levels and you're going to have hyperchilemia, right? So, backtrump is an in a channel blocker.

By blocking in a channel, that's going to reduce the excretion of potassium in the kidneys. And that's going to cause you to retain more potassium. That's going to cause hyperchilemia. All right. So, if you love the way I teach, again, I have a bunch of classes that I think you're absolutely going to love. Like starting today, literally, I have a 20 hour class for step two and step three and level two and three. There's many people that have taken these classes and they've done extremely well. I've had 250's. 250's are not, they're actually pretty common. Again, I'm not saying everyone that takes my class gets a 250. But I've had multiple 250's, like, it's a pretty common occurrence when I would have taken my class. Multiple 260's. I've had a few 270's. I've had a few 280's, right? So, it certainly happens. You can really, really gain a lot by taking these classes. They are over Zoom. And then starting next week, the first two weeks in the month of June, I have this amazing 50 hour step two, step three. You know, obviously also level two, level three class. Again, many people have taken these classes and they don't extremely well with them, right? You want to have an idea of how good these classes will be? Well, you probably have an idea of how I teach. And I'm the one that's gonna teach all these classes, right? And when the one that's gonna teach all these classes, and I've made podcasts where I talk about what you should expect to get from these classes, right?

And then I also offer a four hour biostatistics class, a two and a half hour testicking strategies class and a five hour social sciences quality improvement, hospital medicine, healthcare systems, and ethics class. Those classes offer step one to step three. Those are gonna be taking place in the month of June, in the month of June. And also a four hour one to learn for all the USME Ls and complex exams. I help with your errors, applications, mock interviews, personal statements, and things like that. And then I also have these podcasts on Apple, Google, and Spotify. So check those out, right? Divine intervention podcasts. And I also have a You Tube channel, Divine Intervention, podcasts and videos on You Tube where I post the videos that I make. And then finally, I have another website called Divine Intervention Lifelessens.com. Divine Intervention Lifelessens.com. You know, many of you know I'm a Christian. So every week I post like two or three podcasts where from a biblical perspective, I address a life lesson. There's actually an Apple podcast, associated with that called the Divine Intervention Life Lessons Podcast, right? So listen to those. There's more than 300 podcasts on there. Many people listen to those. And you find them to be very helpful, very good for the, for the soul. So thank you for listening to me today. I will see you in episode 607. But please, please, please, and begging you again. This podcast I just made is very, very high-yield.

Please, is very, very high-yield. You're gonna see the stuff on your exams. You're literally gonna see the stuff on your exams. You're gonna be doing yourself a huge disservice if you don't know this material, right? Hey, there's a reason why I learned this material in the first place because guess what? It's important. All right, so thank you for listening to me today. I will see you in the next episode. Have a wonderful day. God bless you and bye for now. Thank you.

Macrolide antibiotics (e.g., clarithromycin).

SSR Is/SNR Is combined with MAO Is, Triptans, or St. John's Wort.

NSAI Ds constrict the afferent arteriole; AC Ei/AR Bs dilate the efferent arteriole, both reducing glomerular hydrostatic pressure.

CYP3 A4. Induction leads to accelerated metabolism and contraceptive failure.

Volume depletion (e.g., due to diuretics), because the body compensates by increasing proximal tubule reabsorption of sodium and lithium.

Carbamazepine, Phenytoin, and Phenobarbital.

Macrolides inhibit CYP3 A4, slowing warfarin metabolism and raising its plasma concentration.

Rifampin (or other strong enzyme inducers).

Reduced GFR due to opposing effects on afferent (NSAID) and efferent (AC Ei/ARB) arteriolar tone.

MAO Is, Triptans, Tramadol, or St. John's Wort.

Both inhibit each other's breakdown (e.g., via CYP enzymes), leading to elevated levels of both drugs and increased risk of myopathy/rhabdomyolysis.

Potassium-sparing diuretics or aldosterone antagonists (e.g., spironolactone).

Macrolides inhibit CYP3 A4, slowing warfarin metabolism and raising its plasma concentration.

Rifampin (or other strong enzyme inducers).

Reduced GFR due to opposing effects on afferent (NSAID) and efferent (AC Ei/ARB) arteriolar tone.

MAO Is, Triptans, Tramadol, or St. John's Wort.

Both inhibit each other's breakdown (e.g., via CYP enzymes), leading to elevated levels of both drugs and increased risk of myopathy/rhabdomyolysis.

Potassium-sparing diuretics or aldosterone antagonists (e.g., spironolactone).